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Sample records for blood-feeding induces reversible

  1. Blood-Feeding Induces Reversible Functional Changes in Flight Muscle Mitochondria of Aedes aegypti Mosquito

    Science.gov (United States)

    Gonçalves, Renata L. S.; Machado, Ana Carolina L.; Paiva-Silva, Gabriela O.; Sorgine, Marcos H. F.; Momoli, Marisa M.; Oliveira, Jose Henrique M.; Vannier-Santos, Marcos A.; Galina, Antonio; Oliveira, Pedro L.; Oliveira, Marcus F.

    2009-01-01

    Background Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energy-transducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito Aedes aegypti, a vector of dengue and yellow fever. Methodology/Principal Findings Blood-feeding caused a reversible reduction in mitochondrial oxygen consumption, an event that was parallel to blood digestion. These changes were most intense at 24 h after blood meal (ABM), the peak of blood digestion, when oxygen consumption was inhibited by 68%. Cytochromes c and a+a 3 levels and cytochrome c oxidase activity of the electron transport chain were all reduced at 24 h ABM. Ultrastructural and molecular analyses of FM revealed that mitochondria fuse upon blood meal, a condition related to reduced ROS generation. Consistently, BF induced a reversible decrease in mitochondrial H2O2 formation during blood digestion, reaching their lowest values at 24 h ABM where a reduction of 51% was observed. Conclusion Blood-feeding triggers functional and structural changes in hematophagous insect mitochondria, which may represent an important adaptation to blood feeding. PMID:19924237

  2. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  3. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

    International Nuclear Information System (INIS)

    Chelis, Leonidas; Kakolyris, Stylianos; Souftas, Vasilios; Amarantidis, Kiriakos; Xenidis, Nikolaos; Chamalidou, Eleni; Dimopoulos, Prokopios; Michailidis, Prodromos; Christakidis, Evagelos; Prassopoulos, Panagiotis

    2012-01-01

    The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should

  4. Acetylcholinesterases of Blood-feeding Flies and Ticks

    Science.gov (United States)

    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, ...

  5. The role of cystatins in tick physiology and blood feeding

    Czech Academy of Sciences Publication Activity Database

    Schwarz, Alexandra; Valdés, James J.; Kotsyfakis, Michalis

    2012-01-01

    Roč. 3, č. 3 (2012), s. 117-127 ISSN 1877-959X R&D Projects: GA ČR GAP502/12/2409 Institutional research plan: CEZ:AV0Z60220518 Keywords : Cystatin * Cysteine proteases * Tick * Immunomodulators * Blood feeding * Midgut * Physiology Subject RIV: EC - Immunology Impact factor: 2.353, year: 2012

  6. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

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    Ru-Yin Tsai

    2016-06-01

    Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

  7. Inducing Sex Reversal in Marsupial Mammals.

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    Chew, Keng Y; Renfree, Marilyn B

    2016-01-01

    Marsupials are born with undifferentiated gonads, and their reproductive organs differentiate consecutively, not simultaneously as in eutherian mammals. Thus, in the main marsupial model, the tammar wallaby, Macropus eugenii, the testis forms cords 2 days after birth, the ovary develops cortex and medulla about 8 days after birth, the Wolffian duct enlarges from day 10, the prostate begins to form prostatic buds about 25 days after birth, and the phallus does not become sexually dimorphic until after 50 days postpartum (pp). The brain responses also become sexually dimorphic relatively late in development, after day 25 pp. This relatively elongated period of differentiation has allowed experimental manipulation at each stage of development to induce often dramatic sex reversal of both internal and external genitalia. © 2016 S. Karger AG, Basel.

  8. Multiple blood feeding and host-seeking behavior in Aedes aegypti and Aedes albopictus (Diptera: Culicidae).

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    Farjana, Thahsin; Tuno, Nobuko

    2013-07-01

    The body size of mosquitoes can influence a number of bionomic factors, such as their blood-feeding ability, host attack rate, and fecundity. All of these traits are important determinants of their potential to transmit diseases. Among abiotic and biotic factors, high temperature and low nutrition in the developing stages of mosquitoes generally result in small adults. We studied the relationship between body size and multiple feeding in a gonotrophic cycle and some fecundity attributes by using three strains of two competent vector species, Aedes aegypti (L.) and Aedes albopictus (Skuse). We raised small and large mosquitoes under low and high food conditions in the laboratory to measure parameters of fecundity and blood-feeding behavior. Fecundity was positively correlated with body size in both species, whereas the number of bloodmeals, the frequency of host-seeking behavior, and egg retention were negatively correlated with body size in the Ae. albopictus Nagasaki strain. We found that multiple feeding and host-seeking behavior were negatively correlated with body size, i.e., small mosquitoes tended to have more contact with hosts. We found that two mechanisms that inhibit engorged mosquitoes from seeking out hosts, distension-induced and oocyte-induced inhibition, were not strong enough to limit host-seeking behavior, and multiple feeding increased fecundity. Size-dependent multiple feeding and host-seeking behavior affect contact frequency with hosts and should be considered when predicting how changes in mosquito body size affect disease transmission.

  9. Evolution of the salivary apyrases of blood-feeding arthropods.

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    Hughes, Austin L

    2013-09-15

    Phylogenetic analyses of three families of arthropod apyrases were used to reconstruct the evolutionary relationships of salivary-expressed apyrases, which have an anti-coagulant function in blood-feeding arthropods. Members of the 5'nucleotidase family were recruited for salivary expression in blood-feeding species at least five separate times in the history of arthropods, while members of the Cimex-type apyrase family have been recruited at least twice. In spite of these independent events of recruitment for salivary function, neither of these families showed evidence of convergent amino acid sequence evolution in salivary-expressed members. On the contrary, in the 5'-nucleotide family, salivary-expressed proteins conserved ancestral amino acid residues to a significantly greater extent than related proteins without salivary function, implying parallel evolution by conservation of ancestral characters. This unusual pattern of sequence evolution suggests the hypothesis that purifying selection favoring conservation of ancestral residues is particularly strong in salivary-expressed members of the 5'-nucleotidase family of arthropods because of constraints arising from expression within the vertebrate host. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Simple blood-feeding method for live imaging of gut tube remodeling in regenerating planarians.

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    Hosoda, Kazutaka; Morimoto, Mizuki; Motoishi, Minako; Nishimura, Osamu; Agata, Kiyokazu; Umesono, Yoshihiko

    2016-04-01

    Live cell imaging is a powerful technique to study cellular dynamics in vivo during animal development and regeneration. However, few live imaging methods have been reported for studying planarian regeneration. Here, we developed a simple method for steady visualization of gut tube remodeling during regeneration of a living freshwater planarian, Dugesia japonica. When planarians were fed blood several times, gut branches were well-visualized in living intact animals under normal bright-field illumination. Interestingly, tail fragments derived from these colored planarians enabled successive observation of the processes of the formation of a single anterior gut branch in the prepharyngeal region from the preexisting two posterior gut branches in the same living animals during head regeneration. Furthermore, we combined this method and RNA interference (RNAi) and thereby showed that a D. japonica raf-related gene (DjrafA) and mek-related gene (DjmekA) we identified both play a major role in the activation of extracellular signal-regulated kinase (ERK) signaling during planarian regeneration, as indicated by their RNAi-induced defects on gut tube remodeling in a time-saving initial screening using blood-feeding without immunohistochemical detection of the gut. Thus, this blood-feeding method is useful for live imaging of gut tube remodeling, and provides an advance for the field of regeneration study in planarians. © 2016 Japanese Society of Developmental Biologists.

  11. Multitasking roles of mosquito labrum in oviposition and blood feeding

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    Young-Moo eChoo

    2015-10-01

    with 4EP, i.e., they engaged more rapidly in continuous blood feeding as compared to untreated blood. The time of engagement for feeding in skatole-containing blood vs. untreated blood did not differ significantly. Taken together, these data suggest that 4EP reception by the labrum is important not only for oviposition decisions, but also for reducing probing and initiation of blood feeding.

  12. Blood-feeding ecology of mosquitoes in zoos.

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    Tuten, H C; Bridges, W C; Paul, K S; Adler, P H

    2012-12-01

    To determine if the unique host assemblages in zoos influence blood-feeding by mosquitoes (Diptera: Culicidae), a sampling programme was conducted in Greenville and Riverbanks Zoos, South Carolina, U.S.A., from April 2009 to October 2010. A total of 4355 female mosquitoes of 14 species were collected, of which 106 individuals of nine species were blood-fed. The most common taxa were Aedes albopictus (Skuse), Aedes triseriatus (Say), Anopheles punctipennis (Say), Culex erraticus (Dyar & Knab), Culex pipiens complex (L.) and Culex restuans (Theobald). Molecular analyses (cytochrome b) of bloodmeals revealed that mosquitoes fed on captive animals, humans and wildlife, and took mixed bloodmeals. Host species included one amphibian, 16 birds, 10 mammals (including humans) and two reptiles. Minimum dispersal distances after feeding on captive hosts ranged from 15.5 m to 327.0 m. Mosquito-host associations generally conformed to previous accounts, indicating that mosquito behaviour inside zoos reflects that outside zoos. However, novel variation in host use, including new, exotic host records, warrants further investigation. Zoos, thus, can be used as experiment environments in which to study mosquito behaviour, and the findings extrapolated to non-zoo areas, while providing medical and veterinary benefits to zoo animals, employees and patrons. © 2012 The Authors. Medical and Veterinary Entomology © 2012 The Royal Entomological Society.

  13. Adult mortality and blood feeding behavioral effects of α-amyrin acetate, a novel bioactive compound on in vivo exposed females of Anopheles stephensi Liston (Diptera: Culicidae).

    Science.gov (United States)

    Chenniappan, Kuppusamy; Kadarkari, Murugan

    2012-06-01

    The effect of α-amyrin acetate on mortality and blood feeding behavior in females of Anopheles stephensi was assessed by in vivo exposure on treated guinea pig skin. In vivo exposure to α-amyrin acetate caused mosquito knock down in the form of rapidly and normally reversible paralysis and the subsequent record at the end of a 24 h, revealed mortality rates of females increased from 0.0% (Control) to 76.9% at 1.6% α-amyrin acetate, the highest concentration which implies the contact toxicity of the α-amyrin acetate received through the sensitive parts of test species. The mean probing time responses significantly increased (P blood feeding rates and the mean engorgement times were significantly shorter when compared to the control. The mean blood feeding rates of exposed females decreased from 91.7% (control) to 41.5% at 0.8% α-amyrin acetate concentrations, the mean engorgement time also decreased from 278.6 s (Control) to 158.7 s at 0.8% α-amyrin acetate concentrations. Mean blood feeding rates and mean engorgement time were statistically significant (P blood meal size have played a more important role in decline of fecundity. In vivo exposure to α-amyrin acetate caused increased mean probing time, decreased blood engorgement time and feeding rate and declined fecundity which reduce the overall survival and reproductive capacity of the malaria vector A. stephensi.

  14. Blood feeding position increases success of recalcitrant mosquitoes.

    Science.gov (United States)

    Lyski, Zoe L; Saredy, Jason J; Ciano, Kristen A; Stem, Jenna; Bowers, Doria F

    2011-08-01

    Aedes aegypti and Aedes albopictus are competent natural and laboratory vectors for numerous arthropod-borne viruses (arboviruses), many of which pose global public health concerns. Efficiently imbibing a blood meal from an artificial membrane feeder, Ae. aegypti is an easy feeder: ∼ 96% success. Alternatively, Ae. albopictus is known to be a difficult feeder imbibing poorly: ∼ 20% success. Adult female mosquitoes were grouped in cohorts of 50, proffered a bovine blood meal, and challenged with experimental variables, and feeding success was documented. Controls included Ae. aegypti and the artificial glass membrane feeder: topside presentation (upside-down feeding position only). Variables included lambskin versus bovine collagen sausage membranes, presence or absence of gentle motion, filial generations, and large or small blood packets positioned differently: horizontal presentation (right side-up or nose-up feeding position) and vertical presentation (nose-up feeding position only). Both species preferred sausage casings, and ultrastructural analysis revealed that sausage casings had a textured gripping surface not observed on lambskin membranes. Neither filial generations nor gentle motion improved feeding; however, a 32%-46% increase in blood feeding was observed when Ae. albopictus fed on large horizontal and large or small vertical blood packets. Upside-down feeding of Ae. albopictus with a blood suspension of Sindbis virus heat resistant (SVHR) and the original isolate (AR339) resulted in virus dissemination of 10% and 50%, respectively. Use of bovine collagen sausage membranes in a vertical feeding position will increase the number of engorged females, thereby substantially increasing the number of arbovirus-exposed organisms in the laboratory. Differences in blooding success in response to feeding position further separates the behavior attributes of two Aedine species. Blood meal presentation facilitates gravity and we suggest this is a deciding

  15. Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

    Science.gov (United States)

    Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

    2016-05-12

    The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

  16. Effect of photoperiod on blood feeding activity of female hybrids between Culex pipiens pipiens and Culex pipiens quinquefasciatus (Diptera: Culicidae)

    OpenAIRE

    Kurokawa, Kenji; Yoshii, Manabu; Oda, Tsutomu; Kato, Katsutomo; Uchida, Keikichi; Eshita, Yuki; Tahara, Hiroyuki; Mine, Mariko; Ogawa, Yasunori

    2004-01-01

    Blood feeding activity was examined in females of hybrids (F1) between Culex pipiens pipiens and Culex pipiens quinquefasciatus in long and short photoperiods at 2l℃ to examine the effect of photoperiod on blood feeding rate. Blood feeding rates (F1) were lower in short photoperiods than in long photoperiods. From this, it seems that the hybrids show diapause.

  17. Light-induced reversible expansion of individual gold nanoplates

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    Jinsheng Lu

    2017-10-01

    Full Text Available Light-induced mechanical response of materials has been extensively investigated and widely utilized to convert light energy into mechanical energy directly. The metallic nanomaterials have excellent photothermal properties and show enormous potential in micromechanical actuators, etc. However, the photo-thermo-mechanical properties of individual metallic nanostructures have yet to be well investigated. Here, we experimentally demonstrate a way to realize light-induced reversible expansion of individual gold nanoplates on optical microfibers. The light-induced thermal expansion coefficient is obtained as 21.4 ± 4.6 ∼ 31.5 ± 4.2 μ·K-1 when the light-induced heating temperature of the gold nanoplates is 240 ∼ 490 °C. The photo-thermo-mechanical response time of the gold nanoplates is about 0.3 ± 0.1 s. This insight into the photo-thermo-mechanical properties of the gold nanoplates could deepen the understanding of the light-induced reversible expansion behavior in nanoscale and pave the way for applications based on this piezoelectric-like response, such as light-driven metallic micromotors.

  18. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  19. Selenium reverses Pteridium aquilinum-induced immunotoxic effects.

    Science.gov (United States)

    Latorre, A O; Caniceiro, B D; Wysocki, H L; Haraguchi, M; Gardner, D R; Górniak, S L

    2011-02-01

    We have previously shown that bracken fern (Pteridium aquilinum) has immunomodulatory effects on mouse natural killer (NK) cells by reducing cytotoxicity. Alternatively, it has been demonstrated that selenium can enhance NK cell activity. Therefore, the aims of the present study were to evaluate if ptaquiloside, the main toxic component found in P. aquilinum, is responsible for the immunotoxic effects observed in mice, and if selenium supplementation could prevent or even reverse these effects. Male C57BL/6 mice were administered the P. aquilinum extract by daily gavage for 30 days, and histological analyses revealed a significant reduction in splenic white pulp area that was fully reversed by selenium treatment. In addition, mice administered ptaquiloside by daily gavage for 14 days demonstrated the same reduction of NK cell activity as the P. aquilinum extract, and this reduction was prevented by selenium co-administration. Lastly, non-adherent splenic cells treated in vitro with an RPMI extract of P. aquilinum also showed diminished NK cell activity that was not only prevented by selenium co-treatment but also fully reversed by selenium post-treatment. The results of this study clearly show that the immunosuppressive effects of P. aquilinum are induced by ptaquiloside and that selenium supplementation can prevent as well as reverse these effects. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Temperature gradient-induced magnetization reversal of single ferromagnetic nanowires

    Science.gov (United States)

    Michel, Ann-Kathrin; Corinna Niemann, Anna; Boehnert, Tim; Martens, Stephan; Montero Moreno, Josep M.; Goerlitz, Detlef; Zierold, Robert; Reith, Heiko; Vega, Victor; Prida, Victor M.; Thomas, Andy; Gooth, Johannes; Nielsch, Kornelius

    2017-12-01

    In this study, we investigate the temperature- and temperature gradient-dependent magnetization reversal process of individual, single-domain Co39Ni61 and Fe15Ni85 ferromagnetic nanowires via the magneto-optical Kerr effect and magnetoresistance measurements. While the coercive fields (H C) and therefore the magnetic switching fields (H SW) generally decrease under isothermal conditions at elevated base temperatures (T base), temperature gradients (ΔT) along the nanowires lead to an increased switching field of up to 15% for ΔT  = 300 K in Co39Ni61 nanowires. This enhancement is attributed to a stress-induced, magneto-elastic anisotropy term due to an applied temperature gradient along the nanowire that counteracts the thermally assisted magnetization reversal process. Our results demonstrate that a careful distinction between locally elevated temperatures and temperature gradients has to be made in future heat-assisted magnetic recording devices.

  1. Reversal of aflatoxin induced liver damage by turmeric and curcumin.

    Science.gov (United States)

    Soni, K B; Rajan, A; Kuttan, R

    1992-09-30

    The effect of certain food additives on aflatoxin production by Aspergillus parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa), garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the aflatoxin production considerably (more than 90%) at concentrations of 5-10 mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the antioxidant principle from Curcuma longa did not have any effect on aflatoxin production. Turmeric and curcumin were also found to reverse the aflatoxin induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia produced by AFB1 were considerably reversed by these food additives.

  2. HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy.

    Science.gov (United States)

    Krukowski, Karen; Ma, Jiacheng; Golonzhka, Olga; Laumet, Geoffroy O; Gutti, Tanuja; van Duzer, John H; Mazitschek, Ralph; Jarpe, Matthew B; Heijnen, Cobi J; Kavelaars, Annemieke

    2017-06-01

    Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin-dependent intracellular mitochondrial transport. Here, we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. We used a novel HDAC6 inhibitor ACY-1083, which shows 260-fold selectivity towards HDAC6 vs other HDACs. Our results show that HDAC6 inhibition prevented cisplatin-induced mechanical allodynia, and also completely reversed already existing cisplatin-induced mechanical allodynia, spontaneous pain, and numbness. These findings were confirmed using the established HDAC6 inhibitor ACY-1215 (Ricolinostat), which is currently in clinical trials for cancer treatment. Mechanistically, treatment with the HDAC6 inhibitor increased α-tubulin acetylation in the peripheral nerve. In addition, HDAC6 inhibition restored the cisplatin-induced reduction in mitochondrial bioenergetics and mitochondrial content in the tibial nerve, indicating increased mitochondrial transport. At a later time point, dorsal root ganglion mitochondrial bioenergetics also improved. HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.

  3. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    Science.gov (United States)

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  4. Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

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    Gabriela Carrasco-Torres

    2017-01-01

    Full Text Available Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.

  5. Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

    Science.gov (United States)

    Monroy-Ramírez, Hugo Christian; Martínez-Guerra, Arturo Axayacatl; Baltiérrez-Hoyos, Rafael; Romero-Tlalolini, María de los Ángeles; Villa-Treviño, Saúl; Sánchez-Chino, Xariss

    2017-01-01

    Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1. PMID:28740570

  6. Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice.

    Directory of Open Access Journals (Sweden)

    Maria Franca Marongiu

    Full Text Available Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes. Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/- mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/- only in absence of doxycycline (Dox. In such mice, under Dox(+ or vehicle, as well as in wild-type (WT and CB1(-/-, two endophenotypes motor activity (increased in animal models of schizophrenia and pre-pulse inhibition (PPI of startle reflex (disrupted in schizophrenia were analyzed. Both CB1(-/- and IRh-CB1(-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/- animals, was on the contrary highly and significantly disrupted only in Dox(+ IRh-CB1(-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in

  7. The effect of multiple blood-feeding on the longevity and insecticide resistant phenotype in the major malaria vector Anopheles arabiensis (Diptera: Culicidae).

    Science.gov (United States)

    Oliver, Shüné V; Brooke, Basil D

    2014-08-23

    Anopheles arabiensis is a major malaria vector in Africa. Adult females are likely to imbibe multiple blood meals during their lifetime. This results in regular exposure to potential toxins and blood-meal induced oxidative stress. Defence responses to these stressors may affect other factors of epidemiological significance, such as insecticide resistance and longevity. The aims of this study were to examine the effect of multiple blood-feeding on insecticide tolerance/resistance with increasing age, to assess the underlying biochemical mechanisms for the responses recorded, and to assess the effect of multiple blood-feeding on the life histories of adult females drawn from insecticide resistant and susceptible laboratory reared An. arabiensis. Laboratory reared An. arabiensis females from an insecticide resistant and an insecticide susceptible colony were offered either a single blood meal or multiple blood meals at 3-day intervals. Their tolerance or resistance to insecticide was then monitored by WHO bioassay four hours post blood-feeding. The biochemical basis of the phenotypic response was assessed by examining the effect of blood on detoxification enzyme activity and the effect of blood-meals on detoxification enzyme activity in ageing mosquitoes. Control cohorts that were not offered any blood meals showed steadily decreasing levels of insecticide tolerance/resistance with age, whereas a single blood meal significantly increased tolerance/resistance primarily at the age of three days. The expression of resistance/tolerance in those cohorts fed multiple blood meals generally showed the least variation with age. These results were consistent following exposure to DDT and pyrethroids but not to malathion. Multiple blood-meals also maintained the DDT and permethrin resistant phenotype, even after treatment females had stopped taking blood-meals. Biochemical analysis suggests that this phenotypic effect in resistant females may be mediated by the maintenance of

  8. Inducing sex reversal of the urogenital system of marsupials.

    Science.gov (United States)

    Renfree, Marilyn B; Chew, Keng Yih; Shaw, Geoff

    2014-01-01

    Marsupials differ from eutherian mammals in their reproductive strategy of delivering a highly altricial young after a short gestation. The young, with its undeveloped organ systems completes its development post-natally, usually within a pouch. The young is dependent on milk with a composition that varies through lactation to support its growth and changing needs as it matures over a lengthy period. Gonadal differentiation occurs after birth, providing a unique opportunity to examine the effects of hormonal manipulations on its sexual differentiation of the highly accessible young. In marsupials a difference in the migration of the urinary ducts around the genital ducts from eutherian mammals results in the unique tammar reproductive tract which has three vaginae and two cervices, and two distinctly separate uteri. In the tammar wallaby, a small member of the kangaroo family, we showed that virilisation of the Wolffian duct, prostate and phallus depends on an alternate androgen pathway, which has now been shown to be important for virilisation in humans. Through hormonal manipulations over differing time periods we have achieved sex reversal of both ovaries and testes, germ cells, genital ducts, prostate and phallus. Whilst we understand many of the mechanisms behind sexual differentiation there are still many lessons to be learned from understanding how sex reversal is achieved by using a model such as the tammar wallaby. This will help guide investigations into the major questions of how and why sex determination is achieved in other species. This review discusses the control and development of the marsupial urogenital system, largely drawn from our studies in the tammar wallaby and our ability to manipulate this system to induce sex reversal. Copyright © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  9. Colonization of Lutzomyia shannoni (Diptera: Psychodidae) utilizing an artificial blood feeding technique.

    Science.gov (United States)

    Mann, Rajinder S; Kaufman, Phillip E

    2010-12-01

    Laboratory colonization of hematophagous insects must include an efficient method of blood feeding, preferably by artificial means. Strict rules for obtaining animal use permits, extensive animal maintenance costs, and indirect anesthesia effects on animal health warrant the development of an artificial membrane feeding technique for sand fly colonization in laboratories. An attempt was made to colonize Lutzomyia shannoni using an artificial blood feeding membrane to replace the use of live animals commonly used for sand fly blood-feeding purposes. Lutzomyia shannoni readily fed through a pig intestine membrane exposed at an angle of 45°. However, it did not feed through a chicken skin membrane. Olfactory attractants were unable to improve blood-feeding efficiency. Plaster of Paris was the most suitable oviposition substrate. Female L. shannoni adults laid no eggs on moist sand substrate. Sand fly adults held in groups of ten or more laid higher numbers of eggs than did individually maintained sand flies. Inclusion of the L. longipalpis oviposition hormone dodecanoic acid or the presence of previously laid eggs did not stimulate L. shannoni oviposition. The average L. shannoni egg, larval, and pupal duration were 9.3, 36.7, and 17.8 days, respectively. The addition of a 20% sugar solution improved adult female longevity. Females survived longer (14.8 days) than males (11.9 days). Lutzomyia shannoni was successfully colonized in the laboratory for up to four generations using this artificial membrane technique. © 2010 The Society for Vector Ecology.

  10. Human Blood Feeding Activity of Female Hybrids between Culex pipiens pipiens and Culex pipiens quinquefasciatus(Diptera: Culicidae)

    OpenAIRE

    Yoshii, Manabu; Mine, Mariko; Kurokawa, Kenji; Oda, Tsutomu; Kato, Katsutomo; Ogawa, Yasunori; Eshita, Yuuki; Uchida, Keikichi

    2007-01-01

    Human blood feeding activity was examined in females of hybrids between Culex pipiens pipiens and Culex pipiens quinquefasciatus during long photoperiod at 25℃. Blood feeding rates of hybrids were lower than in Culex pipiens quinquefasciatus and Culex pipiens pallens, and higher than in Culex pipiens pipiens, because no females fed on human blood in Culex pipiens pipiens.

  11. Reverse 201Tl myocardial redistribution induced by coronary artery spasm

    International Nuclear Information System (INIS)

    Xiang Dingcheng; Yin Jilin; Gong Zhihua; Xie Zhenhong; Zhang Jinhe; Wen Yanfei; Yi Shaodong

    2010-01-01

    Objective: To investigate the mechanism of reverse redistribution (RR) on dipyridamole 201 Tl myocardial perfusion studies in the patients with coronary artery spasm. Methods: Twenty-six patients with coronary artery spasm and presented as RR on dipyridamole 201 Tl myocardial perfusion studies were enlisted as RR group, while other 16 patients with no coronary artery stenosis nor RR were enlisted as control group. Dipyridamole test was repeated during coronary angiography. Corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) were measured at RR related and non-RR related coronary arteries before and after dipyridamole infusion respectively. All of the data were analyzed by Student's t-test or χ 2 -test and correlation analysis. Results: Coronary artery angiography showed slower blood flow and lower myocardial perfusion in RR related vessels when compared with non-RR related vessels in RR group, but there was no significant difference among the main coronary arteries in control group. The perfusion defects of RR area at rest were positively related to slower blood velocity at corresponding coronary arteries (r = 0.79, t =10.18, P 0.05). Conclusion: RR is related to the decreased blood flow and myocardial perfusion induced by coronary artery spasm at rest, which may be improved by stress test such as intravenous dipyridamole infusion. (authors)

  12. Electric-field induced magnetization reversal using multiferroics

    Science.gov (United States)

    Trassin, Morgan

    2012-02-01

    Controlling magnetism using solely electric fields is interesting not only from a fundamental standpoint, but presents great potential for ultimately low energy consumption logic and memory. The evidence of the electrically controllable antiferromagnetic ordering in the multiferroic magnetoelectric bismuth ferrite (BiFeO3) drew an increasing interest in the pursuit for new emerging devices. To use such functionality for device applications, deterministic control not only of antiferromagnetism, but also ferromagnetism is essential. To achieve this goal, a ferromagnet/multiferroic heterostructure has been proposed based on the combination of magnetoelectric coupling in BiFeO3 and exchange coupling between magnetic materials and offers a new pathway for the electrical control of magnetism. By combination of a piezoresponse force microscopy, photoemission electron microscopy and anisotropic magnetoresistance measurements, we demonstrated the non-volatile reversal of a CoFe layer magnetization induced solely by the application of an electric field at room temperature. This 180 degree rotation of the magnetization of the ferromagnetic layer is mediated by a strong interfacial coupling. The correlation between the ferroelectric state in the multiferroic layer and the CoFe ferromagnetic domain architecture is evidenced. The projection of this strong magnetoelectric coupling in an out-of-plane configuration, allowing the reduction by an order of magnitude of voltage required, will be discussed. Our results show the high potential of magnetoelectric-based heterostructures for future low energy consumption data storage devices.

  13. Sindbis virus infection alters blood feeding responses and DEET repellency in Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Qualls, Whitney A; Day, Jonathan F; Xue, Rui-De; Bowers, Doria F

    2012-03-01

    Aedes aegypti (L.) (Diptera: Culicidae) female mosquitoes infected systemically with Sindbis virus (SINV) took longer than uninfected mosquitoes to locate and fully engorge on blood. On days 7 and 14 postexposure, blood feeding took 1.3 and 1.5 times longer in mosquitoes with a disseminated SINV infection, respectively. SINV dissemination did not affect the average weight of unfed Ae. aegypti, but did result in a 10 and 12% increase in blood imbibed compared with mosquitoes without a positive SINV dissemination and non-SINV-exposed mosquitoes, respectively. Ae. aegypti mosquitoes with a disseminated SINV infection fed an average of 4 h sooner than uninfected mosquitoes when offered a bloodmeal contained inside a DEET (N,N-diethyl-3-methylbenzamide) saturated (30%) bovine sausage casing. Together, these results indicate that behavioral changes in mosquito host-seeking, blood feeding and sensitivity to DEET occurred in mosquitoes after SINV infection and dissemination.

  14. Identification of Salivary Gland Proteins Depleted after Blood Feeding in the Malaria Vector Anopheles campestris-like Mosquitoes (Diptera: Culicidae)

    OpenAIRE

    Sor-suwan, Sriwatapron; Jariyapan, Narissara; Roytrakul, Sittiruk; Paemanee, Atchara; Phumee, Atchara; Phattanawiboon, Benjarat; Intakhan, Nuchpicha; Chanmol, Wetpisit; Bates, Paul A.; Saeung, Atiporn; Choochote, Wej

    2014-01-01

    Malaria sporozoites must invade the salivary glands of mosquitoes for maturation before transmission to vertebrate hosts. The duration of the sporogonic cycle within the mosquitoes ranges from 10 to 21 days depending on the parasite species and temperature. During blood feeding salivary gland proteins are injected into the vertebrate host, along with malaria sporozoites in the case of an infected mosquito. To identify salivary gland proteins depleted after blood feeding of female Anopheles ca...

  15. The reversal of light-induced degradation in amorphous silicon solar cells by an electric field

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, D.E.; Rajan, K. [Solarex, a Business Unit of Amoco/Enron Solar, Newtown, Pennsylvania 19840 (United States)

    1997-04-01

    A strong electric field has been shown to reverse the light-induced degradation of amorphous silicon solar cells while exposed to intense illumination at moderate temperatures. The rate of reversal increases with temperature, illumination intensity, and with the strength of the reverse bias field. The reversal process exhibits an activation energy on the order of 0.9 eV and can be increased by the trapping of either electrons or holes in the presence of a strong electric field. {copyright} {ital 1997 American Institute of Physics.}

  16. Seasonal blood-feeding behavior of Culex tarsalis (Diptera: Culicidae) in Weld County, Colorado, 2007.

    Science.gov (United States)

    Kent, Rebekah; Juliusson, Lara; Weissmann, Michael; Evans, Sara; Komar, Nicholas

    2009-03-01

    Studies on Culex tarsalis Coquillett in Colorado have shown marked seasonal variation in the proportion of blood meals from birds and mammals. However, limitations in the specificity of antibodies used in the precipitin test and lack of vertebrate host availability data warrant revisiting Cx. tarsalis blood feeding behavior in the context of West Nile virus (WNV) transmission. We characterized the host preference of Cx. tarsalis during peak WNV transmission season in eastern Colorado and estimated the relative contribution of different avian species to WNV transmission. Cx. tarsalis preferred birds to mammals each month, although the proportion of blood meals from mammals increased in July and August. The distribution of blood meals differed significantly across months, in part because of changes in the proportion of blood meals from American robins, a preferred host. The estimated proportion of WNV-infectious vectors derived from American robins declined from 60 to 1% between June and August. The majority of avian blood meals came from doves, preferred hosts that contributed 25-40% of the WNV-infectious mosquitoes each month. Active WNV transmission was observed in association with a large house sparrow communal roost. These data show how seasonal patterns in Cx. tarsalis blood feeding behavior relate to WNV transmission in eastern Colorado, with the American robin contributing greatly to early-season virus transmission and a communal roost of sparrows serving as a focus for late-season amplification.

  17. Emerging roles of aquaporins in relation to the physiology of blood-feeding arthropods.

    Science.gov (United States)

    Benoit, Joshua B; Hansen, Immo A; Szuter, Elise M; Drake, Lisa L; Burnett, Denielle L; Attardo, Geoffrey M

    2014-10-01

    Aquaporins (AQPs) are proteins that span plasma membranes allowing the movement of water and small solutes into or out of cells. The type, expression levels and activity of AQPs play a major role in the relative permeability of each cell to water or other solutes. Research on arthropod AQPs has expanded in the last 10 years due to the completion of several arthropod genome projects and the increased availability of genetic information accessible through other resources such as de novo transcriptome assemblies. In particular, there has been significant advancement in elucidating the roles that AQPs serve in relation to the physiology of blood-feeding arthropods of medical importance. The focus of this review is upon the significance of AQPs in relation to hematophagy in arthropods. This will be accomplished via a narrative describing AQP functions during the life history of hematophagic arthropods that includes the following critical phases: (1) Saliva production necessary to blood feeding, (2) Intake and excretion of water during blood digestion, (3) Reproduction and egg development and (4) Off-host environmental stress tolerance. The concentration on these phases will highlight known vulnerabilities in the biology of hematophagic arthropods that could be used to develop novel control strategies as well as research topics that have yet to be examined.

  18. Form, function and evolution of the mouthparts of blood-feeding Arthropoda.

    Science.gov (United States)

    Krenn, Harald W; Aspöck, Horst

    2012-03-01

    This review compares the mouthparts and their modes of operation in blood-feeding Arthropoda which have medical relevance to humans. All possess piercing blood-sucking proboscides which exhibit thin stylet-shaped structures to puncture the host's skin. The tips of the piercing structures are serrated to provide anchorage. Usually, the piercing organs are enveloped by a soft sheath-like part which is not inserted. The piercing process includes either back and forth movements of the piercing structures, or sideways cutting motions, or the apex of the proboscis bears teeth-like structures which execute drilling movements. Most piercing-proboscides have a food-canal which is separate from a salivary canal. The food-canal is functionally connected to a suction pump in the head that transports blood into the alimentary tract. The salivary canal conducts saliva to the tip of the proboscis, from where it is discharged into the host. Piercing blood-sucking proboscides evolved either from (1) generalized biting-chewing mouthparts, (2) from piercing mouthparts of predators, or plant sap or seed feeders, (3) from lapping or sponging mouthparts. Representatives of one taxon of Acari liquefy skin tissue by enzymatic action. During feeding, many blood-feeding arthropods inadvertently transmit pathogens, which mostly are transported through the discharged saliva into the host. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  19. Olanzapine-induced electroencephalographic changes reversed by lamotrigine

    Directory of Open Access Journals (Sweden)

    Prasuna L Velur

    2012-01-01

    Full Text Available The atypical neuroleptic, olanzapine (OLZ, may induce electroencephalographic (EEG abnormalities. The anticonvulsant, lamotrigine (LMG, reduces interictal epileptiform discharges and is effective in seizures in patients with both primary and partial epilepsy syndromes. The effect of LMG on neuroleptic-induced EEG abnormalities has not been previously reported. We describe the case of a 13-year-old male with paroxysmal nonepileptic spells who underwent diagnostic video-EEG telemetry, whose abnormal OLZ-induced EEG findings were strikingly affected by LTG withdrawal and reintroduction. The effect of LTG in normalizing EEG changes in suspected epilepsy caused by atypical neuroleptics is discussed.

  20. Piracetam reverses haloperidol-induced catalepsy in mice

    OpenAIRE

    SALAM, Omar Abdel; NADA, Somaia

    2011-01-01

    To investigate the memory-enhancing drugs piracetam, vinpocetine, and ginkgo biloba for their ability to reduce catalepsy in mice treated with haloperidol. Haloperidol is a classic neuroleptic drug that induces motor abnormalities and cognitive impairment due to a blockade of dopamine D2 receptors in the striatum. Materials and methods: Catalepsy was induced by intraperitoneal haloperidol (2 mg/kg) administration. The drugs being tested were either administered intraperitoneally (IP) along ...

  1. Comparative expression profile of microRNAs in Anopheles anthropophagus midgut after blood-feeding and Plasmodium infection.

    Science.gov (United States)

    Liu, Wenquan; Hao, Zhenhua; Huang, Liyang; Chen, Lingzi; Wei, Qimei; Cai, Liya; Liang, Shaohui

    2017-02-16

    Anopheles anthropophagus is one of the major vectors of malaria in Asia. MicroRNAs (miRNAs) play important roles in cell development and differentiation as well as in the cellular response to stress and infection. In a former study, we have investigated the global miRNA profiles in relation to sex in An. anthropophagus. However, the miRNAs contributing to the blood-feeding and infection with Plasmodium are still unknown. High-throughput sequencing was performed to identify miRNA profiles of An. anthropophagus midguts after blood-feeding and Plasmodium infection. The expression patterns of miRNA in different midgut libraries were compared based on transcripts per million reads (TPM), and further confirmed by Northern blots. Target prediction and pathway analysis were carried out to investigate the role of regulated miRNAs in blood-feeding and Plasmodium infection. We identified 67 known and 21 novel miRNAs in all three libraries (sugar-feeding, blood-feeding and Plasmodium infection) in An. anthropophagus midguts. Comparing with the sugar-feeding, the experssion of nine (6 known and 3 novel) and ten (9 known and 1 novel) miRNAs were significantly upregulated and downregulated respectively after blood-feeding (P anti-parasite immunity.

  2. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    Directory of Open Access Journals (Sweden)

    Oluwafeyisetan O. Adebiyi

    2015-12-01

    Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

  3. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

    Directory of Open Access Journals (Sweden)

    Laura Andrea León A

    2013-01-01

    Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

  4. Cereblon (CRBN) deletion reverses streptozotocin induced diabetic osteoporosis in mice.

    Science.gov (United States)

    Yao, Cong; Guo, Xiong; Yao, Wan-Xia; Zhang, Chun

    2018-02-12

    Diabetes mellitus is a major cause to induce osteoporosis. Though the pathogenesis of osteoporosis progression has been well investigated, its still not fully understood. Recently, cereblon (CRBN) was considered as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. Here, we presented results indicating that CRBN could effectively regulate osteoporosis development. In STZ-induced wild type (WT) mice with diabetes, the osteoclasts were highly increased along with the deterioration of bone structure. However, CRBN knockout (KO) reduced blood glucose the levels and attenuated insulin resistance. What's more, CRBN ablation suppressed osteoclast differentiation and rescued diabetic bone loss in vivo, accompanied with decreased receptor activator of NF-kB ligand (RANKL), RANKL/osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) levels, as well as improved AMP-activated kinase (AMPK) α/acetyl-CoA carboxylase (ACC)αactivation. In vitro, suppressing CRBN expression could reduce RANKL-induced osteoclastogenesis, supported by the reduction of TRAP-positive cells. CRBN knockdown (KD) obviously reduced RANKL-induced activity of IκBα/nuclear factor-κB (NF-κB) pathway. In addition, osteoclast-specific genes expression levels stimulated by RANKL were also decreased by CRBN silence. More importantly, CRBN blockage increased phosphorylated AMPK-α and ACC-α expressions in RANKL-incubated cells. However, these processes could be abolished by suppressing AMPK-α with its inhibitor, Compound C. Collectively, our data suggested that CRBN is a potential treatment option against diabetes-induced osteolytic bone disease. Copyright © 2018. Published by Elsevier Inc.

  5. Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

    Science.gov (United States)

    Yamamoto, D S; Nagumo, H; Yoshida, S

    2010-06-01

    'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

  6. Countercurrent heat exchange and thermoregulation during blood-feeding in kissing bugs.

    Science.gov (United States)

    Lahondère, Chloé; Insausti, Teresita C; Paim, Rafaela Mm; Luan, Xiaojie; Belev, George; Pereira, Marcos H; Ianowski, Juan P; Lazzari, Claudio R

    2017-11-21

    Blood-sucking insects experience thermal stress at each feeding event on endothermic vertebrates. We used thermography to examine how kissing-bugs Rhodnius prolixus actively protect themselves from overheating. During feeding, these bugs sequester and dissipate the excess heat in their heads while maintaining an abdominal temperature close to ambient. We employed a functional-morphological approach, combining histology, µCT and X-ray-synchrotron imaging to shed light on the way these insects manage the flow of heat across their bodies. The close alignment of the circulatory and ingestion systems, as well as other morphological characteristics, support the existence of a countercurrent heat exchanger in the head of R. prolixus , which decreases the temperature of the ingested blood before it reaches the abdomen. This kind of system has never been described before in the head of an insect. For the first time, we show that countercurrent heat exchange is associated to thermoregulation during blood-feeding.

  7. An insight into the sialotranscriptome of the non-blood feeding Toxorhynchites amboinensis mosquito.

    Science.gov (United States)

    Calvo, E; Pham, V M; Ribeiro, J M C

    2008-05-01

    All adult mosquitoes take sugar meals, and most adult females also take blood meals to develop eggs. Salivary glands (SG) of males are thus much smaller and do not contain many of the antihemostatic and antiinflammatory compounds found in females. In the past 5 years, transcriptome analyses have identified nearly 70 different genes expressed in adult female SG. For most of these, no function can be assigned in either blood or sugar feeding. Exceptionally, Toxorhynchites mosquitoes are unusual in that they never feed on blood, and the SG of adults are identical in both sexes. Transcriptome analysis of the adult SG of this mosquito was performed to increase knowledge of the evolution of blood feeding--and to identify polypeptide families associated with sugar feeding--in mosquitoes.

  8. La Crosse virus infection alters blood feeding behavior in Aedes triseriatus and Aedes albopictus (Diptera: Culicidae).

    Science.gov (United States)

    Jackson, Bryan T; Brewster, Carlyle C; Paulson, Sally L

    2012-11-01

    The effects of La Crosse virus (LACV) infection on blood feeding behavior in Aedes triseriatus (Say) and Aedes albopictus (Skuse) were investigated in the laboratory by measuring the size of the bloodmeal imbibed and the extent of refeeding by virus-infected and uninfected mosquitoes. LACV-infected Ae. triseriatus and Ae. albopictus took significantly less blood compared with uninfected mosquitoes. Twice as many virus-infected Ae. triseriatus mosquitoes refed compared with uninfected individuals (18 vs. 9%; P < 0.05); however, virus infection had no significant effect on the refeeding rate of Ae. albopictus. Reduction in bloodmeal size followed by an increased avidity for refeeding may lead to enhanced horizontal transmission of the LACV by its principal vector, Ae. triseriatus.

  9. Countercurrent heat exchange and thermoregulation during blood-feeding in kissing bugs

    Science.gov (United States)

    Lahondère, Chloé; Insausti, Teresita C; Belev, George; Pereira, Marcos H

    2017-01-01

    Blood-sucking insects experience thermal stress at each feeding event on endothermic vertebrates. We used thermography to examine how kissing-bugs Rhodnius prolixus actively protect themselves from overheating. During feeding, these bugs sequester and dissipate the excess heat in their heads while maintaining an abdominal temperature close to ambient. We employed a functional-morphological approach, combining histology, µCT and X-ray-synchrotron imaging to shed light on the way these insects manage the flow of heat across their bodies. The close alignment of the circulatory and ingestion systems, as well as other morphological characteristics, support the existence of a countercurrent heat exchanger in the head of R. prolixus, which decreases the temperature of the ingested blood before it reaches the abdomen. This kind of system has never been described before in the head of an insect. For the first time, we show that countercurrent heat exchange is associated to thermoregulation during blood-feeding. PMID:29157359

  10. Comparative studies on the biology and filarial susceptibility of selected blood-feeding and autogenous Aedes togoi sub-colonies

    Directory of Open Access Journals (Sweden)

    Anuluck Junkum

    2003-06-01

    Full Text Available Blood-feeding and autogenous sub-colonies were selected from a laboratory, stock colony of Aedes togoi, which was originally collected from Koh Nom Sao, Chanthaburi province, Southeast Thailand. Comparative biology and filarial susceptibility between the two sub-colonies (blood-feeding: F11, F13; autogeny: F38, F40 were investigated to evaluate their viability and vectorial capacity. The results of comparison on biology revealed intraspecific differences, i.e., the average egg deposition/gravid female (F11/F38; F13/F40, embryonation rate (F13/F40, hatchability rate (F11/F38; F13/F40, egg width (F11/F38, wing length of females (F13/F40, and wing length and width of males (F11/F38 in the blood-feeding sub-colony were significantly greater than that in the autogenous sub-colony; and egg length (F11/F38 and width (F13/F40, and mean longevity of adult females (F11/F38 and males (F13/F40 in the blood-feeding sub-colony were significantly less than that in the autogenous sub-colony. The results of comparison on filarial susceptibility demonstrated that both sub-colonies yielded similar susceptibilities to Brugia malayi [blood-feeding/autogeny = 56.7% (F11/53.3%(F38, 60%(F13/83.3%(F40] and Dirofilaria immitis [blood-feeding/autogeny = 85.7%(F11/75%(F38, 45%(F13/29.4%(F40], suggesting autogenous Ae. togoi sub-colony was an efficient laboratory vector in study of filariasis.

  11. Effects of temperature on development, mortality, mating and blood feeding behavior of Culiseta incidens (Diptera: Culicidae).

    Science.gov (United States)

    Su, T; Mulla, M S

    2001-06-01

    Culiseta incidens Thomson is distributed over most of the western USA and Canada northward to Alaska. Because this mosquito is difficult to colonize, its biology has not been well investigated. We colonized this species in 1998 and studied the effects of temperature on various aspects of its life cycle. The time required for egg melanization and the duration of the egg stage were negatively correlated with temperature. The proportion of fertile egg rafts was temperature-independent. An inverse relationship existed between temperature and egg hatch. Molting and stadium duration after hatching were temperature-dependent, with higher temperature accelerating development and molting. Larvae and pupae experienced lower mortality and higher molting success at lower temperatures. Survivorship of adult mosquitoes fed on sugar solution was inversely proportional to temperature, lethal times for 50% mortality (LT50) were greater at the lower temperature than at the higher temperature. Females survived longer than did males at all test temperatures. Because this species is eurygamous, mating only occurred in large cages. Mating success was also affected by temperature. At the test temperatures, 20 degrees C, 25 degrees C and 30 degrees C, mating started from 3-5 days after emergence and reached a peak on days 13-15 after emergence. Maximum mating rates at 20 degrees C and 25 degrees C were higher than at 30 degrees C. Blood feeding, as indicated by cumulative feeding rates, was affected by cage size, mosquito age and temperature. Mosquitoes in large cages exhibited a much higher feeding rate than in small cages. With age, the cumulative blood feeding rate increased, with the highest rate at 25 degrees C, followed by 20 degrees C and 30 degrees C. At all temperatures tested, most of the blood fed females were mated.

  12. The Investigation of Strain-Induced Martensite Reverse Transformation in AISI 304 Austenitic Stainless Steel

    Science.gov (United States)

    Cios, G.; Tokarski, T.; Żywczak, A.; Dziurka, R.; Stępień, M.; Gondek, Ł.; Marciszko, M.; Pawłowski, B.; Wieczerzak, K.; Bała, P.

    2017-10-01

    This paper presents a comprehensive study on the strain-induced martensitic transformation and reversion transformation of the strain-induced martensite in AISI 304 stainless steel using a number of complementary techniques such as dilatometry, calorimetry, magnetometry, and in-situ X-ray diffraction, coupled with high-resolution microstructural transmission Kikuchi diffraction analysis. Tensile deformation was applied at temperatures between room temperature and 213 K (-60 °C) in order to obtain a different volume fraction of strain-induced martensite (up to 70 pct). The volume fraction of the strain-induced martensite, measured by the magnetometric method, was correlated with the total elongation, hardness, and linear thermal expansion coefficient. The thermal expansion coefficient, as well as the hardness of the strain-induced martensitic phase was evaluated. The in-situ thermal treatment experiments showed unusual changes in the kinetics of the reverse transformation (α' → γ). The X-ray diffraction analysis revealed that the reverse transformation may be stress assisted—strains inherited from the martensitic transformation may increase its kinetics at the lower annealing temperature range. More importantly, the transmission Kikuchi diffraction measurements showed that the reverse transformation of the strain-induced martensite proceeds through a displacive, diffusionless mechanism, maintaining the Kurdjumov-Sachs crystallographic relationship between the martensite and the reverted austenite. This finding is in contradiction to the results reported by other researchers for a similar alloy composition.

  13. Stress-induced antinociception in fish reversed by naloxone.

    Directory of Open Access Journals (Sweden)

    Carla Patrícia Bejo Wolkers

    Full Text Available Pain perception in non-mammalian vertebrates such as fish is a controversial issue. We demonstrate that, in the fish Leporinus macrocephalus, an imposed restraint can modulate the behavioral response to a noxious stimulus, specifically the subcutaneous injection of 3% formaldehyde. In the first experiment, formaldehyde was applied immediately after 3 or 5 min of the restraint. Inhibition of the increase in locomotor activity in response to formaldehyde was observed, which suggests a possible restraint-induced antinociception. In the second experiment, the noxious stimulus was applied 0, 5, 10 and 15 min after the restraint, and both 3 and 5 min of restraint promoted short-term antinociception of approximately 5 min. In experiments 3 and 4, an intraperitoneal injection of naloxone (30 mg.kg(-1 was administered 30 min prior to the restraint. The 3- minute restraint-induced antinociception was blocked by pretreatment with naloxone, but the corresponding 5-minute response was not. One possible explanation for this result is that an opioid and a non-preferential μ-opioid and/or non-opioid mechanism participate in this response modulation. Furthermore, we observed that both the 3- and 5- minutes restraint were severely stressful events for the organism, promoting marked increases in serum cortisol levels. These data indicate that the response to a noxious stimulus can be modulated by an environmental stressor in fish, as is the case in mammals. To our knowledge, this study is the first evidence for the existence of an endogenous antinociceptive system that is activated by an acute standardized stress in fish. Additionally, it characterizes the antinociceptive response induced by stress in terms of its time course and the opioid mediation, providing information for understanding the evolution of nociception modulation.

  14. Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

    Science.gov (United States)

    Jung, Christian; Grün, Katja; Betge, Stefan; Pernow, John; Kelm, Malte; Masyuk, Maryna; Kuethe, Friedhelm; Ndongson-Dongmo, Bernadin; Bauer, Reinhard; Lauten, Alexander; Schulze, P. Christian; Berndt, Alexander

    2017-01-01

    Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH. PMID:28757567

  15. Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice.

    Science.gov (United States)

    Aliotta, Jason M; Pereira, Mandy; Wen, Sicheng; Dooner, Mark S; Del Tatto, Michael; Papa, Elaine; Goldberg, Laura R; Baird, Grayson L; Ventetuolo, Corey E; Quesenberry, Peter J; Klinger, James R

    2016-06-01

    Extracellular vesicles (EVs) from mice with monocrotaline (MCT)-induced pulmonary hypertension (PH) induce PH in healthy mice, and the exosomes (EXO) fraction of EVs from mesenchymal stem cells (MSCs) can blunt the development of hypoxic PH. We sought to determine whether the EXO fraction of EVs is responsible for modulating pulmonary vascular responses and whether differences in EXO-miR content explains the differential effects of EXOs from MSCs and mice with MCT-PH. Plasma, lung EVs from MCT-PH, and control mice were divided into EXO (exosome), microvesicle (MV) fractions and injected into healthy mice. EVs from MSCs were divided into EXO, MV fractions and injected into MCT-treated mice. PH was assessed by right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. miR microarray analyses were also performed on all EXO populations. EXOs but not MVs from MCT-injured mice increased RV/LV + S, WT/D ratios in healthy mice. MSC-EXOs prevented any increase in RV/LV + S, WT/D ratios when given at the time of MCT injection and reversed the increase in these ratios when given after MCT administration. EXOs from MCT-injured mice and patients with idiopathic pulmonary arterial hypertension (IPAH) contained increased levels of miRs-19b,-20a,-20b, and -145, whereas miRs isolated from MSC-EXOs had increased levels of anti-inflammatory, anti-proliferative miRs including miRs-34a,-122,-124, and -127. These findings suggest that circulating or MSC-EXOs may modulate pulmonary hypertensive effects based on their miR cargo. The ability of MSC-EXOs to reverse MCT-PH offers a promising potential target for new PAH therapies. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  16. Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Christian Jung

    2017-07-01

    Full Text Available Pulmonary hypertension (PH is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose. There were three experimental groups: sham-treated controls (control group, n = 11, MCT-induced PH (MCT group, n = 11 and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13. ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg compared to the control group (41 ± 15 mmHg, p = 0.002 accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001. Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01. Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006 and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022. PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.

  17. Arrhythmia-Induced Cardiomyopathy: Prevalent, Under-recognized, Reversible.

    Science.gov (United States)

    Dhawan, Rahul; Gopinathannair, Rakesh

    2017-01-01

    Arrhythmia-induced cardiomyopathy (AIC) is a clinical condition in which a persistent tachyarrhythmia or frequent ectopy contribute to ventricular dysfunction leading to systolic heart failure. AIC can be partially or completely corrected with adequate treatment of the culprit arrhythmia. Several molecular and cellular alterations by which tachyarrhythmias lead to cardiomyopathy have been identified. AIC can affect children and adults, can be clinically silent in the form of asymptomatic tachycardia with cardiomyopathy, or can present with manifest heart failure. A high index of suspicion for AIC and aggressive treatment of the culprit arrhythmia can result in resolution of heart failure symptoms and improvement in cardiac function. Recurrent arrhythmia, following recovery from the index episode, can hasten the left ventricular dysfunction and result in HF, suggesting persistent adverse remodeling despite recovery of left ventricular function. Several aspects of AIC, such as predisposing factors, early diagnosis, preventive measures to avoid adverse remodeling, and long-term prognosis, remain unclear, and need further research.

  18. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  19. Evolutionary Changes in Sensitivity to Hormonally Induced Gonadal Sex Reversal in a Frog Species.

    Science.gov (United States)

    Miura, Ikuo; Ohtani, Hiromi; Ogata, Mitsuaki; Ezaz, Tariq

    2016-01-01

    The Japanese frog Glandirana rugosa is unique in that it shows geographic variation in sex chromosome differentiation and heterogametic sex determination. To elucidate the cause of interpopulation differences in gonadal sex differentiation, we investigated hormonally induced sex reversal and the expression patterns of genes associated with sex determination during early tadpole development. We found that sex reversal was easily induced in XX females and XY males of 2 forms (West-Japan and East-Japan) of G. rugosa with the ancestral homomorphic sex chromosomes under male heterogametic sex determination. During sex reversal, expression of CYP19 and/or FOXL2 was dependent on the phenotypic sex of the gonad. In contrast, sex reversal was not induced in ZW females of a population with a heteromorphic ZW sex chromosome system or in XX females or XY males in a population with a heteromorphic XY sex chromosome system. The latter 2 populations are evolutionarily derived forms. These results indicate an evolutionary direction for the gonadal sex differentiation mechanism. The original system was highly sensitive to sex hormones and allowed almost complete sex reversal. From this ancestral form, a new system evolved that was resistant to hormones and showed a change in the heterogametic sex and the sex chromosome differentiation mechanism. © 2016 S. Karger AG, Basel.

  20. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  1. Photon-Induced Magnetization Reversal in Single Molecule Magnets

    Science.gov (United States)

    Bal, Mustafa

    2005-03-01

    Single-molecule magnets (SMM) have been the subject of intensive research for more than a decade now because of their unique properties such as macroscopic quantum tunneling. Recent work in this area is focused on whether SMM are potential qubits, as proposed theoretically [1]. We use continuous millimeter wave radiation to manipulate the populations of the energy levels of a single crystal molecular magnet Fe8 [2]. When radiation is in resonance with the transitions between energy levels, the steady state magnetization exhibits dips. As expected, the magnetic field locations of these dips vary linearly with the radiation frequency. We will describe our experimental results, which provide a lower bound of 0.17 ns for transverse relaxation time. Transitions between excited states are found even though these states have negligible population at the experimental temperature. We find evidence that the sample heating is significant when the resonance condition is satisfied. Recent experiments are concentrated on the spin dynamics of Fe8 induced by pulsed radiation and results of these studies will also be presented. [1] Leuenberger, M. N. and Loss, D., Nature 410, 789 (2001). [2] M. Bal et al., Phys. Rev. B 70, 100408(R) (2004).

  2. Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans

    Science.gov (United States)

    Roux, Antoine E.; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

    2017-01-01

    Summary Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly-hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(−) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

  3. Differential expression of Ixodes ricinus tick genes induced by blood feeding or Borrelia burgdorferi infection

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Edwards, M. J.; Grubhoffer, Libor

    2005-01-01

    Roč. 42, č. 1 (2005), s. 36-41 ISSN 0022-2585 R&D Projects: GA AV ČR IAA6022306 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * Borrelia burgdorferi * subtractive hybridization Subject RIV: EE - Microbiology, Virology Impact factor: 1.489, year: 2005

  4. Studies on the post-oviposition blood-feeding behaviour of Aedes aegypti (L.) (Diptera: Culicidae) in the laboratory.

    Science.gov (United States)

    Chadee, D D

    2012-11-01

    The blood-feeding behaviour of the Trinidad strain of Aedes aegypti was studied, under laboratory conditions, using one female per cage and monitoring blood feeding immediately, 12, and 24 hours after oviposition. To get large numbers of females that had newly completed their first gonotrophic cycle, the diel oviposition periodicity was conducted using single females per cage and monitoring at 2-hour intervals. The diel oviposition periodicity showed a small morning peak (8%) during the first 2 hours of the photophase after which oviposition declined: during the second half of the photophase, oviposition increased reaching a peak comprising 56% of eggs (G = 59·9, P>0·01) between 16:00 and 18:00 hours. At post-oviposition hour 0, only five (10%) of the females accepted a blood meal but at post-oviposition hour 12, significantly more (G = 46·98, P>0·02) females, 35 (70%) accepted a blood meal. This pattern was consistently observed when females were offered blood meals at 12 and 24 hours after completing their first gonotrophic cycle. Multiple feeding was observed among the blood-feeding females and the results of this study are discussed in the context of disease transmission patterns and physiological mechanisms which control their blood-feeding behaviours.

  5. Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine.

    Directory of Open Access Journals (Sweden)

    Jason M Williams

    2007-10-01

    Full Text Available The behavioral effects of psychomotor stimulants such as amphetamine (AMPH arise from their ability to elicit increases in extracellular dopamine (DA. These AMPH-induced increases are achieved by DA transporter (DAT-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ. In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K and protein kinase B (PKB, or Akt, which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level-dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders.

  6. Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Wetterslev, J; Jarnvig, I; Jørgensen, L N

    1991-01-01

    The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose...

  7. Circadian clock of Aedes aegypti: effects of blood-feeding, insemination and RNA interference

    Science.gov (United States)

    Gentile, Carla; Rivas, Gustavo Bueno da S; Lima, José BP; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio

    2013-01-01

    Mosquitoes are the culprits of some of the most important vector borne diseases. A species’ potential as a vector is directly dependent on their pattern of behaviour, which is known to change according to the female’s physiological status such as whether the female is virgin/mated and unfed/blood-fed. However, the molecular mechanism triggered by and/or responsible for such modulations in behaviour is poorly understood. Clock genes are known to be responsible for the control of circadian behaviour in several species. Here we investigate the impact mating and blood-feeding have upon the expression of these genes in the mosquito Aedes aegypti . We show that blood intake, but not insemination, is responsible for the down-regulation of clock genes. Using RNA interference, we observe a slight reduction in the evening activity peak in the fourth day after dstim injection. These data suggest that, as in Drosophila , clock gene expression, circadian behaviour and environmental light regimens are interconnected in Ae. aegypti . PMID:24473806

  8. Seasonal abundance and blood feeding activity of Anopheles minimus Theobald (Diptera: Culicidae) in Thailand.

    Science.gov (United States)

    Chareonviriyaphap, Theeraphap; Prabaripai, Atchariya; Bangs, Michael J; Aum-Aung, Boonserm

    2003-11-01

    Anopheline mosquito larvae and adults were sampled at Ban Pu Teuy, Tri-Yok District, Kanchanaburi Province, western Thailand, from January 2000 to December 2001. Over the period of 2 yr, Anopheles minimus sensu lato was the most commonly collected species, followed by Anopheles swadiwongporni and Anopheles dirus sensu lato; all three species are important vectors of malaria in Thailand. Attempted blood feeding by An. minimus occurred throughout the night, with two distinct feeding peaks: strong activity immediately after sunset (1800-2100 hours), followed by a second, less pronounced, rise before sunrise (0300-0600 hours). Anopheles minimus were more abundant during the wet season compared with the dry and hot seasons, although nocturnal adult feeding patterns were similar. Anopheles minimus fed readily on humans inside and outside of houses, showing a slight preference for exophagy. The human-biting peak of An. minimus in our study area differed from other localities sampled in Thailand, indicating the possible existence of site-specific populations of An. minimus exhibiting different host-seeking behavior. These results underscore the importance of conducting site-specific studies to accurately determine vector larval habitats and adult activity patterns and linking their importance in malaria transmission in a given area.

  9. Feeding through artificial membranes reduces fecundity for females of the blood-feeding insect, Rhodnius prolixus.

    Science.gov (United States)

    Chiang, R Gary; Chiang, Jennifer A

    2010-06-01

    The blood-feeding insect, Rhodnius prolixus, has been raised in the laboratory for close to 100 years. Various feeding techniques have been employed ranging from the use of warm-blooded hosts, to the use of previously collected blood offered through artificial membranes. This study compared the fecundity in mated and unmated females fed rabbit blood directly from the shaved belly of a rabbit to that of females fed defibrinated rabbit blood through an artificial membrane. These results confirm previous reports that this insect's feeding efficacy is reduced using an artificial membrane. It also demonstrates for the first time that the fecundity index, which measures the efficiency of turning the blood meal into eggs, is significantly reduced. We suggest that the natural feeding on a warm-blooded host may provide cues that have the short-term effect of enhancing the act of feeding and the long-term effect of increasing egg production efficiency. Until an artificial feeding method that does not interfere with feeding and fecundity is devised, experiments on reproduction in R. prolixus warrant the use of a warm-blooded host to emulate feeding in its natural setting.

  10. Molecular Detection of Bartonella Species in Blood-Feeding Bat Flies from Mexico.

    Science.gov (United States)

    Moskaluk, Alexandra E; Stuckey, Matthew J; Jaffe, David A; Kasten, Rickie W; Aguilar-Setién, Alvaro; Olave-Leyva, José Ignacio; Galvez-Romero, Guillermo; Obregón-Morales, Cirani; Salas-Rojas, Mónica; García-Flores, María Martha; Aréchiga-Ceballos, Nidia; García-Baltazar, Anahí; Chomel, Bruno B

    2018-05-01

    Bartonellae are emerging blood-borne bacteria that have been recovered from a wide range of mammalian species and arthropod vectors around the world. Bats are now recognized as a potential wildlife reservoir for a diverse number of Bartonella species, including the zoonotic Candidatus B. mayotimonensis. These bat-borne Bartonella species have also been detected in the obligate ectoparasites of bats, such as blood-feeding flies, which could transmit these bacteria within bat populations. To better understand this potential for transmission, we investigated the relatedness between Bartonella detected or isolated from bat hosts sampled in Mexico and their ectoparasites. Bartonella spp. were identified in bat flies collected on two bat species, with the highest prevalence in Trichobius parasiticus and Strebla wiedemanni collected from common vampire bats (Desmodus rotundus). When comparing Bartonella sequences from a fragment of the citrate synthase gene (gltA), vector-associated strains were diverse and generally close to, but distinct from, those recovered from their bacteremic bat hosts in Mexico. Complete Bartonella sequence concordance was observed in only one bat-vector pair. The diversity of Bartonella strains in bat flies reflects the frequent host switch by bat flies, as they usually do not live permanently on their bat host. It may also suggest a possible endosymbiotic relationship with these vectors for some of the Bartonella species carried by bat flies, whereas others could have a mammalian host.

  11. Blood-feeding patterns of the Culex pipiens complex in Sacramento and Yolo Counties, California.

    Science.gov (United States)

    Montgomery, Matthew J; Thiemann, Tara; Macedo, Paula; Brown, David A; Scott, Thomas W

    2011-03-01

    Mosquitoes in the Culex pipiens complex are competent vectors of West Nile virus (WNV; family Flaviviridae, genus Flavivirus) in the laboratory, and field-collected mosquitoes have tested positive for the virus in California and elsewhere. A better understanding of Cx. pipiens complex blood-feeding patterns will help define the threat that these mosquitoes pose to human health and their role in WNV amplification in northern California. We collected blood-engorged Cx. pipiens complex mosquitoes from resting sites near and away from human habitation in Sacramento and Yolo Counties. Cytochrome c oxidase 1 gene sequences were used to identify the vertebrate species from which blood meals were taken. Of 330 engorged mosquitoes collected at 28 sites from June through August 2007 and May through August 2008, >99% fed on an avian host. Three mosquitoes contained bovine blood and none had fed on a human. American Robins (Turdus migratorius) were bitten most often, and the proportion of American Robin blood meals increased significantly over the summer. Other important avian hosts included House Finches (Carpodacus mexicanus), Barn Swallows (Hirundo rustica), Western Meadowlarks (Sturnella neglecta), and Mourning Doves (Zenaida macroura). In rural areas, Barn Swallows, Brewer's Blackbirds (Euphagus cyanocephalus), and House Sparrows (Passer domesticus) were frequent hosts. In settings near human habitation, Mourning Doves and Western Meadowlarks were common hosts. Our data indicate that in north central California mosquitoes in the Cx. pipiens complex may be more important as epiornitic than epidemic vectors of WNV.

  12. X-ray irradiation induced reversible resistance change in Pt/TiO2/Pt cells.

    Science.gov (United States)

    Chang, Seo Hyoung; Kim, Jungho; Phatak, Charudatta; D'Aquila, Kenneth; Kim, Seong Keun; Kim, Jiyoon; Song, Seul Ji; Hwang, Cheol Seong; Eastman, Jeffrey A; Freeland, John W; Hong, Seungbum

    2014-02-25

    The interaction between X-rays and matter is an intriguing topic for both fundamental science and possible applications. In particular, synchrotron-based brilliant X-ray beams have been used as a powerful diagnostic tool to unveil nanoscale phenomena in functional materials. However, it has not been widely investigated how functional materials respond to the brilliant X-rays. Here, we report the X-ray-induced reversible resistance change in 40-nm-thick TiO2 films sandwiched by Pt top and bottom electrodes, and propose the physical mechanism behind the emergent phenomenon. Our findings indicate that there exists a photovoltaic-like effect, which modulates the resistance reversibly by a few orders of magnitude, depending on the intensity of impinging X-rays. We found that this effect, combined with the X-ray irradiation induced phase transition confirmed by transmission electron microscopy, triggers a nonvolatile reversible resistance change. Understanding X-ray-controlled reversible resistance changes can provide possibilities to control initial resistance states of functional materials, which could be useful for future information and energy storage devices.

  13. Low concentrations of dihydrotestosterone induce female-to-male sex reversal in the frog Pelophylax nigromaculatus.

    Science.gov (United States)

    Xu, Wei; Li, Yuan-Yuan; Lou, Qin-Qin; Chen, Xiao-Ran; Qin, Zhan-Fen; Wie, Wu-Ji

    2015-10-01

    Previous studies have demonstrated that some amphibian species can be sex-reversed by high concentrations of androgens. Little attention has focused on the effects of androgenic endocrine-disrupting chemicals (EDCs) on amphibians. The present study aimed to investigate the effects of lower concentrations of the androgenic EDC 5α-dihydrotestosterone (DHT) on gonadal differentiation and development in Pelophylax nigromaculatus, a true frog distributed widely in East Asia. Tadpoles at Gosner stage 24/25 were exposed to nominal concentrations of 40 ng/L, 400 ng/L, and 4000 ng/L DHT to complete metamorphosis. In all DHT treatment groups, males and ambiguous sexes were identified based on gonadal morphology, whereas no females were found; thus, all treatment groups exhibited male-skewed ratios compared with the control group. Gonadal histological examination revealed that ambiguous sexes displayed overall testicular structure with certain ovarian characteristics, demonstrating that DHT-induced sex-ambiguous gonads were incomplete ovary-to-testis reversals (IOTTRs). The expression levels of some ovary-biased genes in the IOTTRs were significantly higher than in the control testes but lower than in the control ovaries. These results show that low concentrations of DHT induced complete or incomplete female-to-male sex reversal in P. nigromaculatus, and incomplete sex reversal retained certain ovarian characteristics not only at gonadal morphological and histological levels but also at the molecular level. They present study highlights potential risks of DHT and other androgenic EDCs for P. nigromaculatus. © 2015 SETAC.

  14. Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Bickelhaupt, Sebastian; Erbel, Christian; Timke, Carmen; Wirkner, Ute; Dadrich, Monika; Flechsig, Paul; Tietz, Alexandra; Pföhler, Johanna; Gross, Wolfgang; Peschke, Peter; Hoeltgen, Line; Katus, Hugo A; Gröne, Hermann-Josef; Nicolay, Nils H; Saffrich, Rainer; Debus, Jürgen; Sternlicht, Mark D; Seeley, Todd W; Lipson, Kenneth E; Huber, Peter E

    2017-08-01

    Radiotherapy is a mainstay for the treatment of lung cancer that can induce pneumonitis or pulmonary fibrosis. The matricellular protein connective tissue growth factor (CTGF) is a central mediator of tissue remodeling. A radiation-induced mouse model of pulmonary fibrosis was used to determine if transient administration of a human antibody to CTGF (FG-3019) started at different times before or after 20 Gy thoracic irradiation reduced acute and chronic radiation toxicity. Mice (25 mice/group; 10 mice/group in a confirmation study) were examined by computed tomography, histology, gene expression changes, and for survival. In vitro experiments were performed to directly study the interaction of CTGF blockade and radiation. All statistical tests were two-sided. Administration of FG-3019 prevented (∼50%-80%) or reversed (∼50%) lung remodeling, improved lung function, improved mouse health, and rescued mice from lethal irradiation ( P radiation-induced gene expression changes, and reduced myofibroblast abundance and Osteopontin expression. These results indicate that blocking CTGF attenuates radiation-induced pulmonary remodeling and can reverse the process after initiation. CTGF has a central role in radiation-induced fibrogenesis, and FG-3019 may benefit patients with radiation-induced pulmonary fibrosis or patients with other forms or origin of chronic fibrotic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 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.

  16. Geographical variation in host use of a blood-feeding ectoparasitic fly: implications for population invasiveness.

    Science.gov (United States)

    Välimäki, Panu; Kaitala, Arja; Madslien, Knut; Härkönen, Laura; Várkonyi, Gergely; Heikkilä, Jari; Jaakola, Mervi; Ylönen, Hannu; Kortet, Raine; Ytrehus, Bjørnar

    2011-08-01

    Invasive generalist ectoparasites provide a tool to study factors affecting expansion rates. An increase in the number of host species may facilitate geographic range expansion by increasing the number of suitable habitats and by affecting local extinction and colonization rates. A geographic perspective on parasite host specificity and its implications on range expansion are, however, insufficiently understood. We conducted a field study to explore if divergent host specificity could explain the observed variation in expansion rates between Fennoscandian populations of the deer ked (Lipoptena cervi), which is a blood-feeding ectoparasitic fly of cervids. We found that the rapidly expanding eastern population in Finland appears to specialize on moose, whereas the slowly expanding western population in Norway breeds successfully on both moose and roe deer. The eastern population was also found to utilize the wild forest reindeer as an auxiliary host, but this species is apparently of low value for L. cervi in terms of adult maintenance, reproductive output and offspring quality. Abundant numbers of roe deer and white-tailed deer were observed to be apparently uninfected in Finland, suggesting that host use is not a plastic response to host availability, but rather a consequence of population-level evolutionary changes. Locally compatible hosts were found to be the ones sharing a long history with the deer ked in the area. Cervids that sustained adult deer keds also allowed successful reproduction. Thus, host use is probably determined by the ability of the adult to exploit particular host species. We conclude that a wide host range alone does not account for the high expansion rate or wide geographic distribution of the deer ked, although loose ecological requirements would increase habitat availability.

  17. Dynamics of digestive proteolytic system during blood feeding of the hard tick Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Sojka Daniel

    2010-12-01

    Full Text Available Abstract Background Ticks are vectors of a wide variety of pathogens causing severe diseases in humans and domestic animals. Intestinal digestion of the host blood is an essential process of tick physiology and also a limiting factor for pathogen transmission since the tick gut represents the primary site for pathogen infection and proliferation. Using the model tick Ixodes ricinus, the European Lyme disease vector, we have previously demonstrated by genetic and biochemical analyses that host blood is degraded in the tick gut by a network of acidic peptidases of the aspartic and cysteine classes. Results This study reveals the digestive machinery of the I. ricinus during the course of blood-feeding on the host. The dynamic profiling of concentrations, activities and mRNA expressions of the major digestive enzymes demonstrates that the de novo synthesis of peptidases triggers the dramatic increase of the hemoglobinolytic activity along the feeding period. Overall hemoglobinolysis, as well as the activity of digestive peptidases are negligible at the early stage of feeding, but increase dramatically towards the end of the slow feeding period, reaching maxima in fully fed ticks. This finding contradicts the established opinion that blood digestion is reduced at the end of engorgement. Furthermore, we show that the digestive proteolysis is localized intracellularly throughout the whole duration of feeding. Conclusions Results suggest that the egressing proteolytic system in the early stage of feeding and digestion is a potential target for efficient impairment, most likely by blocking its components via antibodies present in the host blood. Therefore, digestive enzymes are promising candidates for development of novel 'anti-tick' vaccines capable of tick control and even transmission of tick-borne pathogens.

  18. Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization

    OpenAIRE

    Auffenberg, Eva; Jurik, Angela; Mattusch, Corinna; Stoffel, Rainer; Genewsky, Andreas; Namendorf, Christian; Schmid, Roland M.; Rammes, Gerhard; Biel, Martin; Uhr, Manfred; Moosmang, Sven; Michalakis, Stylianos; Wotjak, Carsten T.; Thoeringer, Christoph K.

    2016-01-01

    Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type ...

  19. Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

    Science.gov (United States)

    Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

    2018-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Effects of Preexposure to DEET on the Downstream Blood-Feeding Behaviors of Aedes aegypti (Diptera: Culicidae) Mosquitoes.

    Science.gov (United States)

    Sugiharto, Victor A; Grieco, John P; Murphy, Jittawadee R; Olsen, Cara H; Colacicco-Mayhugh, Michelle G; Stewart, V Ann; Achee, Nicole L; Turell, Michael J

    2016-06-10

    Mosquito behavior is heavily influenced by the chemical molecules in the environment. This knowledge can be used to modify insect behaviors; particularly to reduce vector-host contact as a powerful method for disease prevention. N,N-Diethyl-meta-toluamide (DEET) is the most widely used insect repellent in the market and an excellent example of a chemical that has been used to modify insect behavior for disease prevention. However, genetic insensitivity and habituation in Aedes aegypti (L.) mosquitoes after preexposure to DEET have been reported. In this study, we investigated the effect of preexposure to DEET on the downstream blood-feeding behavior of Ae. aegypti mosquitoes and the duration of the effect. We exposed mosquitoes to four different DEET concentrations: 0.10, 0.12, 0.14, and 0.16% for 10 min then allowed the mosquitoes to blood-feed on an artificial blood-feeding system either immediately or after being held for 1, 3, 6, or 24 h following DEET exposure. We found that preexposing Ae. aegypti mosquitoes to 0.14 or 0.16% DEET lowered their blood engorgement level, but did not alter their landing and probing behavior when compared to the control test populations. The reduction in complete blood-feeding was observed at all time periods tested, but was only statistically significant at 3 and 6 h after the preexposure process. Because reduction in blood meal has been associated with increased refeeding, future studies analyzing the effect of this behavior using arbovirus-infected mosquitoes are needed to address the concern of potentially increased vectorial capacity. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Identification of salivary gland proteins depleted after blood feeding in the malaria vector Anopheles campestris-like mosquitoes (Diptera: Culicidae.

    Directory of Open Access Journals (Sweden)

    Sriwatapron Sor-suwan

    Full Text Available Malaria sporozoites must invade the salivary glands of mosquitoes for maturation before transmission to vertebrate hosts. The duration of the sporogonic cycle within the mosquitoes ranges from 10 to 21 days depending on the parasite species and temperature. During blood feeding salivary gland proteins are injected into the vertebrate host, along with malaria sporozoites in the case of an infected mosquito. To identify salivary gland proteins depleted after blood feeding of female Anopheles campestris-like, a potential malaria vector of Plasmodium vivax in Thailand, two-dimensional gel electrophoresis and nano-liquid chromatography-mass spectrometry techniques were used. Results showed that 19 major proteins were significantly depleted in three to four day-old mosquitoes fed on a first blood meal. For the mosquitoes fed the second blood meal on day 14 after the first blood meal, 14 major proteins were significantly decreased in amount. The significantly depleted proteins in both groups included apyrase, 5'-nucleotidase/apyrase, D7, D7-related 1, short form D7r1, gSG6, anti-platelet protein, serine/threonine-protein kinase rio3, putative sil1, cyclophilin A, hypothetical protein Phum_PHUM512530, AGAP007618-PA, and two non-significant hit proteins. To our knowledge, this study presents for the first time the salivary gland proteins that are involved in the second blood feeding on the day corresponding to the transmission period of the sporozoites to new mammalian hosts. This information serves as a basis for future work concerning the possible role of these proteins in the parasite transmission and the physiological processes that occur during the blood feeding.

  2. Identification of salivary gland proteins depleted after blood feeding in the malaria vector Anopheles campestris-like mosquitoes (Diptera: Culicidae).

    Science.gov (United States)

    Sor-suwan, Sriwatapron; Jariyapan, Narissara; Roytrakul, Sittiruk; Paemanee, Atchara; Phumee, Atchara; Phattanawiboon, Benjarat; Intakhan, Nuchpicha; Chanmol, Wetpisit; Bates, Paul A; Saeung, Atiporn; Choochote, Wej

    2014-01-01

    Malaria sporozoites must invade the salivary glands of mosquitoes for maturation before transmission to vertebrate hosts. The duration of the sporogonic cycle within the mosquitoes ranges from 10 to 21 days depending on the parasite species and temperature. During blood feeding salivary gland proteins are injected into the vertebrate host, along with malaria sporozoites in the case of an infected mosquito. To identify salivary gland proteins depleted after blood feeding of female Anopheles campestris-like, a potential malaria vector of Plasmodium vivax in Thailand, two-dimensional gel electrophoresis and nano-liquid chromatography-mass spectrometry techniques were used. Results showed that 19 major proteins were significantly depleted in three to four day-old mosquitoes fed on a first blood meal. For the mosquitoes fed the second blood meal on day 14 after the first blood meal, 14 major proteins were significantly decreased in amount. The significantly depleted proteins in both groups included apyrase, 5'-nucleotidase/apyrase, D7, D7-related 1, short form D7r1, gSG6, anti-platelet protein, serine/threonine-protein kinase rio3, putative sil1, cyclophilin A, hypothetical protein Phum_PHUM512530, AGAP007618-PA, and two non-significant hit proteins. To our knowledge, this study presents for the first time the salivary gland proteins that are involved in the second blood feeding on the day corresponding to the transmission period of the sporozoites to new mammalian hosts. This information serves as a basis for future work concerning the possible role of these proteins in the parasite transmission and the physiological processes that occur during the blood feeding.

  3. Salivary Gland Proteome during Adult Development and after Blood Feeding of Female Anopheles dissidens Mosquitoes (Diptera: Culicidae).

    Science.gov (United States)

    Phattanawiboon, Benjarat; Jariyapan, Narissara; Mano, Chonlada; Roytrakul, Sittiruk; Paemanee, Atchara; Sor-Suwan, Sriwatapron; Sriwichai, Patchara; Saeung, Atiporn; Bates, Paul A

    Understanding changes in mosquito salivary proteins during the time that sporozoite maturation occurs and after blood feeding may give information regarding the roles of salivary proteins during the malarial transmission. Anopheles dissidens (formerly Anopheles barbirostris species A1) is a potential vector of Plasmodium vivax in Thailand. In this study, analyses of the proteomic profiles of female An. dissidens salivary glands during adult development and after blood feeding were carried out using two-dimensional gel electrophoresis coupled with nano-liquid chromatography-mass spectrometry. Results showed at least 17 major salivary gland proteins present from day one to day 21 post emergence at 8 different time points sampled. Although there was variation observed, the patterns of protein expression could be placed into one of four groups. Fifteen protein spots showed significant depletion after blood feeding with the percentages of the amount of depletion ranging from 8.5% to 68.11%. The overall results identified various proteins, including a putative mucin-like protein, an anti-platelet protein, a long form D7 salivary protein, a putative gVAG protein precursor, a D7-related 3.2 protein, gSG7 salivary proteins, and a gSG6 protein. These results allow better understanding of the changes of the salivary proteins during the adult mosquito development. They also provide candidate proteins to investigate any possible link or not between sporozoite maturation, or survival of skin stage sporozoites, and salivary proteins.

  4. Meeting the challenges of on-host and off-host water balance in blood-feeding arthropods

    Science.gov (United States)

    Benoit, Joshua B.; Denlinger, David L.

    2010-01-01

    In this review, we describe water balance requirements of blood-feeding arthropods, particularly contrasting dehydration tolerance during the unfed, off-host state and the challenges of excess water that accompany receipt of the bloodmeal. Most basic water balance characteristics during the off-host stage are applicable to other terrestrial arthropods, as well. A well-coordinated suite of responses enable arthropods to conserve water resources, enhance their desiccation tolerance, and increase their water supplies by employing a diverse array of molecular, structural and behavioral responses. Water loss rates during the off-host phase are particularly useful for generating a scheme to classify vectors according to their habitat requirements for water, thus providing a convenient tool with potential predictive power for defining suitable current and future vector habitats. Blood feeding elicits an entirely different set of challenges as the vector responds to overhydration by quickly increasing its rate of cuticular water loss and elevating the rate of diuresis to void excess water and condense the bloodmeal. Immature stages that feed on blood normally have a net increase in water content at the end of a blood-feeding cycle, but in adults the water content reverts to the prefeeding level when the cycle is completed. Common themes are evident in diverse arthropods that feed on blood, particularly the physiological mechanisms used to respond to the sudden influx of water as well as the mechanisms used to counter water shortfalls that are encountered during the nonfeeding, off-host state. PMID:20206630

  5. Inactivation of Ca2+-induced ciliary reversal by high-salt extraction in the cilia of Paramecium.

    Science.gov (United States)

    Kutomi, Osamu; Seki, Makoto; Nakamura, Shogo; Kamachi, Hiroyuki; Noguchi, Munenori

    2013-10-01

    Intracellular Ca(2+) induces ciliary reversal and backward swimming in Paramecium. However, it is not known how the Ca(2+) signal controls the motor machinery to induce ciliary reversal. We found that demembranated cilia on the ciliated cortical sheets from Paramecium caudatum lost the ability to undergo ciliary reversal after brief extraction with a solution containing 0.5 M KCl. KNO(3), which is similar to KCl with respect to chaotropic effect; it had the same effect as that of KCl on ciliary response. Cyclic AMP antagonizes Ca(2+)-induced ciliary reversal. Limited trypsin digestion prevents endogenous A-kinase and cAMP-dependent phosphorylation of an outer arm dynein light chain and induces ciliary reversal. However, the trypsin digestion prior to the high-salt extraction did not affect the inhibition of Ca(2+)-induced ciliary reversal caused by the high-salt extraction. Furthermore, during the course of the high-salt extraction, some axonemal proteins were extracted from ciliary axonemes, suggesting that they may be responsible for Ca(2+)-induced ciliary reversal.

  6. Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

    Directory of Open Access Journals (Sweden)

    V. S. Kulkarni

    2011-09-01

    Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

  7. Local Peltier-effect-induced reversible metal–insulator transition in VO2 nanowires

    International Nuclear Information System (INIS)

    Takami, Hidefumi; Kanki, Teruo; Tanaka, Hidekazu

    2016-01-01

    We report anomalous resistance leaps and drops in VO 2 nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO 2 nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

  8. Local Peltier-effect-induced reversible metal–insulator transition in VO{sub 2} nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Takami, Hidefumi; Kanki, Teruo, E-mail: kanki@sanken.osaka-u.ac.jp, E-mail: h-tanaka@sanken.osaka-u.ac.jp; Tanaka, Hidekazu, E-mail: kanki@sanken.osaka-u.ac.jp, E-mail: h-tanaka@sanken.osaka-u.ac.jp [Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)

    2016-06-15

    We report anomalous resistance leaps and drops in VO{sub 2} nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO{sub 2} nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

  9. Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in the rat.

    Science.gov (United States)

    Prasad, Jyotsna; Baitharu, Iswar; Sharma, Alpesh Kumar; Dutta, Ruma; Prasad, Dipti; Singh, Shashi Bala

    2013-12-01

    Inadequate oxygen availability at high altitude causes elevated oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. Though oxidative stress is known to be a major cause of neurodegeneration in hypobaric hypoxia, neuroprotective and ameliorative potential of quercetin, a flavonoid with strong antioxidant properties in reversing hypobaric hypoxia-induced memory impairment has not been studied. Four groups of male adult Sprague Dawley rats were exposed to hypobaric hypoxia for 7 days in an animal decompression chamber at an altitude of 7600 meters. Rats were supplemented with quercetin orally by gavage during 7 days of hypoxic exposure. Spatial working memory was assessed by a Morris Water Maze before and after exposure to hypobaric hypoxia. Changes in oxidative stress markers and apoptotic marker caspase 3 expression in hippocampus were assessed. Histological assessment of neurodegeneration was performed by cresyl violet and fluoro Jade B staining. Our results showed that quercetin supplementation during exposure to hypobaric hypoxia decreased reactive oxygen species levels and consequent lipid peroxidation in the hippocampus by elevating antioxidant status and free radical scavenging enzyme system. There was reduction in caspase 3 expression, and decrease in the number of pyknotic and fluoro Jade B-positive neurons in hippocampus after quercetin supplementation during hypoxic exposure. Behavioral studies showed that quercetin reversed the hypobaric hypoxia-induced memory impairment. These findings suggest that quercetin provides neuroprotection to hippocampal neurons during exposure to hypobaric hypoxia through antioxidative and anti-apoptotic mechanisms, and possesses promising therapeutic potential to ameliorate hypoxia-induced memory dysfunction.

  10. Reversal by hypothermia of vasodilator-induced tachycardia in anesthetized rats.

    Science.gov (United States)

    Vidrio, H; García-Márquez, F

    1987-08-01

    The normal cardiovascular response to hydralazine in urethane-anesthetized rats, i.e. hypotension and tachycardia, was changed to hypotension and bradycardia if the body temperature of the animals was not maintained constant by external heating, but was allowed to decrease spontaneously throughout the experiment. A similar phenomenon was observed with diazoxide. In rats maintained at a rectal temperature of 31 degrees C, hydralazine bradycardia was partially blocked by a low dose of atropine and was reversed to tachycardia by a high dose of this agent; mecamylamine failed to influence heart rate lowering in this condition. Heart rate responses in unheated animals to acetylcholine and isopropylarterenol were respectively potentiated and depressed when compared to responses in heated rats. These findings suggest that cold-induced reciprocal changes in reactivity of cardiac muscarinic and beta-adrenoceptors may be responsible for reversal of hydralazine or diazoxide tachycardia in urethane-anesthetized hypothermic rats. As a result, cardiac stimulation by the sympatho-adrenal discharge induced by hypotension is inhibited, while cardiac depression which is apparently also induced by hypotension, is facilitated. It is speculated that vasopressin, released as a consequence of the blood pressure fall, could be this negative chronotropic factor.

  11. Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization.

    Science.gov (United States)

    Auffenberg, Eva; Jurik, Angela; Mattusch, Corinna; Stoffel, Rainer; Genewsky, Andreas; Namendorf, Christian; Schmid, Roland M; Rammes, Gerhard; Biel, Martin; Uhr, Manfred; Moosmang, Sven; Michalakis, Stylianos; Wotjak, Carsten T; Thoeringer, Christoph K

    2016-01-13

    Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms.The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research.

  12. Deoxynivalenol-induced weight loss in the diet-induced obese mouse is reversible and PKR-independent.

    Science.gov (United States)

    Flannery, Brenna M; He, Kaiyu; Pestka, James J

    2013-07-31

    The trichothecene deoxynivalenol (DON), a potent ribotoxic mycotoxin produced by the cereal blight fungus Fusarium graminearum, commonly contaminates grain-based foods. Oral exposure to DON causes decreased food intake, reduced weight gain and body weight loss in experimental animals - effects that have been linked to dysregulation of hormones responsible for mediating satiety at the central nervous system level. When diet-induced obese (DIO) mice are fed DON, they consume less food, eventually achieving body weights of control diet-fed mice. Here, we extended these findings by characterizing: (1) reversibility of DON-induced body weight loss and anorexia in DIO mice and (2) the role of double-stranded RNA-activated protein kinase (PKR) which has been previously linked to initiation of the ribotoxic stress response. The results demonstrated that DON-induced weight loss was reversible in DIO mice and this effect corresponded to initiation of a robust hyperphagic response. When DIO mice deficient in PKR were exposed to DON, they exhibited weight suppression similar to DIO wild-type fed the toxin, suggesting the toxin's weight effects were not dependent on PKR. Taken together, DON's effects on food consumption and body weight are not permanent and, furthermore, PKR is not an essential signaling molecule for DON's anorectic and weight effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Dead bacteria reverse antibiotic-induced host defense impairment in burns.

    Science.gov (United States)

    Chen, Lee-Wei; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei

    2014-10-01

    Burn patients can incur high rates of hospital-acquired infections. The mechanism of antibiotic exposure on inducing infection vulnerability has not been determined. This study aimed to examine the effects of antibiotic treatment on host defense mechanisms. First we treated C57/BL6 mice with combined antibiotic treatment after 30% to 35% total body surface area burn. Animals were sacrificed at 48 hours after sham or thermal injury treatment. Bacterial counts in intestinal lumen and mucosa were measured. Next, we treated animals with or without oral dead Escherichia coli or Staphylococcus aureus supplementation to stimulate Toll-like receptor in the intestinal mucosa. Toll-like receptor 4, antibacterial protein expression, nuclear factor (NF)-κB DNA-binding activity, and bacteria-killing activity in the intestinal mucosa; intestinal permeability; bacterial translocation to mesenteric lymph nodes; Klebsiella pneumoniae translocation; interleukin-6 in the blood; and phagocytic activity of alveolar macrophages, were assessed. Thermal injury increased microflora and NF-κB DNA-binding activity of the intestine. Systemic antibiotic treatment decreased gut microflora and increased bacterial translocation to mesenteric lymph nodes, intestinal permeability, and interleukin-6 levels in the blood. Antibiotic treatment also decreased bacteria-killing activity in intestinal mucosa and phagocytic activity of alveolar macrophages. Oral dead E coli and S aureus supplementation induced NF-κB DNA-binding activity, Toll-like receptor 4, and antibacterial protein expression of the intestinal mucosa. Taken together with the fact that dead bacteria reversed antibiotic-induced K pneumoniae translocation and intestinal and pulmonary defense impairment, we conclude that combined antibiotic treatment results in systemic host defense impairment in burns through the decrease in intestinal flora. We suggest that dead bacteria supplementation could induce nondefensin protein expression and

  14. Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

    Science.gov (United States)

    Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

    2018-04-15

    Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

  15. Meeting the challenges of on-host and off-host water balance in blood-feeding arthropods.

    Science.gov (United States)

    Benoit, Joshua B; Denlinger, David L

    2010-10-01

    In this review, we describe water balance requirements of blood-feeding arthropods, particularly contrasting dehydration tolerance during the unfed, off-host state and the challenges of excess water that accompany receipt of the bloodmeal. Most basic water balance characteristics during the off-host stage are applicable to other terrestrial arthropods, as well. A well-coordinated suite of responses enable arthropods to conserve water resources, enhance their desiccation tolerance, and increase their water supplies by employing a diverse array of molecular, structural and behavioral responses. Water loss rates during the off-host phase are particularly useful for generating a scheme to classify vectors according to their habitat requirements for water, thus providing a convenient tool with potential predictive power for defining suitable current and future vector habitats. Blood-feeding elicits an entirely different set of challenges as the vector responds to overhydration by quickly increasing its rate of cuticular water loss and elevating the rate of diuresis to void excess water and condense the bloodmeal. Immature stages that feed on blood normally have a net increase in water content at the end of a blood-feeding cycle, but in adults the water content reverts to the pre-feeding level when the cycle is completed. Common themes are evident in diverse arthropods that feed on blood, particularly the physiological mechanisms used to respond to the sudden influx of water as well as the mechanisms used to counter water shortfalls that are encountered during the non-feeding, off-host state. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Susceptibility of adult female Aedes aegypti (Diptera: Culicidae to the entomopathogenic fungus Metarhizium anisopliae is modified following blood feeding

    Directory of Open Access Journals (Sweden)

    Samuels Richard I

    2011-05-01

    Full Text Available Abstract Background The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Methods Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818 using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Results Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding, host susceptibility to infection returned to pre-blood fed (sucrose fed levels. Conclusions Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged

  17. Susceptibility of adult female Aedes aegypti (Diptera: Culicidae) to the entomopathogenic fungus Metarhizium anisopliae is modified following blood feeding.

    Science.gov (United States)

    Paula, Adriano R; Carolino, Aline T; Silva, Carlos P; Samuels, Richard I

    2011-05-26

    The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818) using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding), host susceptibility to infection returned to pre-blood fed (sucrose fed) levels. Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged periods on fungus impregnated black cloths, thus optimizing infection

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

    Science.gov (United States)

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

    2015-11-01

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

  19. Sarsasapogenin reverses depressive-like behaviors and nicotinic acetylcholine receptors induced by olfactory bulbectomy.

    Science.gov (United States)

    Feng, Bo; Zhao, Xiao-Yang; Song, Yi-Zhou; Liang, Wen-Na; Liu, Ji-Liang

    2017-02-03

    Cholinergic signalling in the hippocampus may contribute to the aetiology of mood regulation. Antidepressants can reverse the increase in acetylcholinesterase (AChE) activity induced by olfactory bulbectomy. The activation of nicotinic acetylcholine receptors (nAChRs) also alleviates the symptoms of depression. This study advances the development of sarsasapogenin, which interacts with cholinergic signalling and has a favourable antidepressant profile in olfactory bulbectomised (OB) rats. We examined OB-induced changes in cholinergic signalling, as well as AChE, α4-nAChR, and α7-nAChR expression in the hippocampus. The results indicate that abnormal cholinergic signalling in the hippocampus contributes to the development of depression in the OB rat model. This depression may be alleviated following treatment with sarsasapogenin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Influence of thermal agitation on the electric field induced precessional magnetization reversal with perpendicular easy axis

    Directory of Open Access Journals (Sweden)

    Hongguang Cheng

    2013-12-01

    Full Text Available We investigated the influence of thermal agitation on the electric field induced precessional magnetization switching probability with perpendicular easy axis by solving the Fokker-Planck equation numerically with finite difference method. The calculated results show that the thermal agitation during the reversal process crucially influences the switching probability. The switching probability can be achieved is only determined by the thermal stability factor Δ of the free layer, it is independent on the device dimension, which is important for the high density device application. Ultra-low error rate down to the order of 10−9 can be achieved for the device of thermal stability factor Δ of 40. Low damping factor α material should be used for the free layer for high reliability device applications. These results exhibit potential of electric field induced precessional magnetization switching with perpendicular easy axis for ultra-low power, high speed and high density magnetic random access memory (MRAM applications.

  1. Influence of thermal agitation on the electric field induced precessional magnetization reversal with perpendicular easy axis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Hongguang, E-mail: chenghg7932@gmail.com; Deng, Ning [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China)

    2013-12-15

    We investigated the influence of thermal agitation on the electric field induced precessional magnetization switching probability with perpendicular easy axis by solving the Fokker-Planck equation numerically with finite difference method. The calculated results show that the thermal agitation during the reversal process crucially influences the switching probability. The switching probability can be achieved is only determined by the thermal stability factor Δ of the free layer, it is independent on the device dimension, which is important for the high density device application. Ultra-low error rate down to the order of 10{sup −9} can be achieved for the device of thermal stability factor Δ of 40. Low damping factor α material should be used for the free layer for high reliability device applications. These results exhibit potential of electric field induced precessional magnetization switching with perpendicular easy axis for ultra-low power, high speed and high density magnetic random access memory (MRAM) applications.

  2. Mouth reversal extinguishes mismatch negativity induced by the McGurk illusion

    DEFF Research Database (Denmark)

    Eskelund, Kasper; Andersen, Tobias

    2013-01-01

    The sight of articulatory mouth movements (visual speech) influences auditory speech perception. This is demonstrated by the McGurk illusion in which incongruent visual speech alters the auditory phonetic percept. In behavioral studies, reversal of the vertical mouth direction has been reported...... to greatly reduce the McGurk illusion (Rosenblum et al., 2000). Such findings support the idea that audiovisual integration in speech to some extent relies on information regarding facial configuration. Here we ask whether this behavioral effect is reflected in a difference in neural activity in the auditory...... cortex. Mismatch Negativity (MMN) is a component in the auditory Event-Related Potential (ERP) that is elicited by a change in the auditory percept. It has been shown that the McGurk illusion can induce a MMN. We conducted an experiment in which the MMN could be elicited by the McGurk illusion induced...

  3. Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

    Science.gov (United States)

    Wu, Dongyuan; Jiang, Zhirong; Gong, Bing; Dou, Yue; Song, Mingxuan; Song, Xiaoxia; Tian, Yu

    2017-10-21

    In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 μg Vit E, or 1.5 mg/kg + 0.1 μg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 μmol/L FA, 25 μmol/L FA, 50 μmol/L FA, 10 mg/L Vit. E, and 50 μmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 μg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

  4. Free radical scavenging reverses fructose-induced salt-sensitive hypertension

    Directory of Open Access Journals (Sweden)

    Zenner ZP

    2017-12-01

    Full Text Available Zachary P Zenner, Kevin L Gordish, William H Beierwaltes Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA Abstract: We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium–hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure. We found that both 20% fructose intake and a high-salt diet stimulated 8-isoprostane excretion. The superoxide dismutase (SOD mimetic tempol significantly reduced this elevated excretion. Next, we placed rats on a high-salt diet (4% for 1 week in combination with normal rat chow or 20% fructose with or without chronic tempol administration. A fructose plus high-salt diet induced a rapid increase (15 mmHg in systolic blood pressure and reversed high salt suppression of plasma renin activity. Tempol treatment reversed the pressor response and restored high salt suppression of renin. We conclude that fructose-induced salt-sensitive hypertension is driven by increased renal reactive oxygen species formation associated with salt retention and an enhanced renin–angiotensin system. Keywords: reactive oxygen species, tempol, sodium, renin, oxidative stress

  5. Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

    Directory of Open Access Journals (Sweden)

    Alireza Abed

    2017-11-01

    Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

  6. Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Vialou, Vincent; Heller, Elizabeth A; Yieh, Lynn; LaBonté, Benoit; Peña, Catherine J; Shen, Li; Wittenberg, Gayle M; Nestler, Eric J

    2017-02-15

    Examining transcriptional regulation by antidepressants in key neural circuits implicated in depression and understanding the relation to transcriptional mechanisms of susceptibility and natural resilience may help in the search for new therapeutic agents. Given the heterogeneity of treatment response in human populations, examining both treatment response and nonresponse is critical. We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine, and a rapidly acting, non-monoamine-based antidepressant, ketamine, in mice subjected to chronic social defeat stress, a validated depression model, and used RNA sequencing to analyze transcriptional profiles associated with susceptibility, resilience, and antidepressant response and nonresponse in the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. We identified similar numbers of responders and nonresponders after ketamine or imipramine treatment. Ketamine induced more expression changes in the hippocampus; imipramine induced more expression changes in the nucleus accumbens and amygdala. Transcriptional profiles in treatment responders were most similar in the PFC. Nonresponse reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptibility-associated transcriptional changes and induced resilience-associated transcription in the PFC. We generated a uniquely large resource of gene expression data in four interconnected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by antidepressant drugs and in both reversing susceptibility- and inducing resilience-associated molecular adaptations. In addition, we found region-specific effects of each drug, suggesting both common and unique effects of imipramine versus ketamine. Copyright © 2016 Society of Biological

  7. Speman®, A Proprietary Ayurvedic Formulation, Reverses Cyclophosphamide-Induced Oligospermia In Rats.

    Directory of Open Access Journals (Sweden)

    Mohd. Azeemuddin Mukram

    2013-04-01

    Full Text Available Background: This investigation was aimed to evaluate the effect of Speman®, a well known ayurvedic proprietary preparation, in an experimental model of cyclophosphamide-(CP induced oligospermia in rats.Materials and Methods: Thirty male rats were randomized in to five, equally-sized groups. Rats in group 1 served as a normal control; group 2 served as an untreated positive control; groups 3, 4, 5 received  Speman® granules  at doses of 300, 600, and 900mg/kg body weight p.o. respectively, once daily for 13 days. On day four, one hour after the respective treatment, oligospermia was induced by administering a single dose of CP (100mg/kg body weight p.o.  to all the groups except group1. At the end of the study period the rats were euthanised and accessory reproductive organs were weighed and subjected to histopathological examination. The semen samples were subject to enumeration of sperms.  Weight of the reproductive organs, histopathological examination of the tissues, and sperm count were the parameters studied to understand the effect of Speman® on rats with CP-induced oligospermia.Results: Changes that occurred due to the administration of CP at a dose of 100 mg/kg body weight were dose dependently reversed with Speman® at a dose of 300, 600, and 900 mg/kg body weight. There was a statistically significant increase in sperm count and the weight of the seminal vesicle, epididymis, and prostate.Conclusion: Findings of this investigation indicate that Speman® dose dependently reversed the CP-induced derangement of various parameters pertaining to the reproductive system.  This could explain the total beneficial actions of Speman® reported in several other clinical trials.

  8. Measurement of the efficacy of 2% lipid in reversing bupivacaine- induced asystole in isolated rat hearts

    Science.gov (United States)

    2014-01-01

    Background The reversal efficacy of 2% lipid emulsion in cardiac asystole induced by different concentrations of bupivacaine is poorly defined and needs to be determined. Methods Forty-two male Sprague–Dawley rats were randomly divided into seven groups: B40, B60, B80, B100, B120, B140 and B160, n = 6. The Langendorff isolated heart perfusion model was used, which consisted of a balanced perfusion with Krebs-Henseleit solution for 25 minutes and a continuous infusion of 100 μmol/L bupivacaine until asystole had been induced for 3 minutes. The hearts in the seven groups were perfused with Krebs-Henseleit solution containing a 2% lipid emulsion, and 40, 60, 80, 100, 120, 140 or 160 μmol/L bupivacaine, respectively. Cardiac recovery was defined as a spontaneous and regular rhythm with a rate-pressure product > 10% of the baseline value for more than 1 minute. Our primary outcome was the rate-pressure product 25 minutes after cardiac recovery. Other cardiac function parameters were also recorded. Results All groups demonstrated cardiac recovery. During the recovery phase, heart rate, rate-pressure product, the maximum left ventricular pressure rise and decline in heart rate in the B120-B160 groups was significantly lower than those in the B40-B80 groups (P bupivacaine and the reversal effects of a 2% lipid emulsion showed a typical transoid S-shaped curve, R2 = 0.9983, IC50 value was 102.5 μmol/L (95% CI: 92.44 - 113.6). Conclusions There is a concentration-response relationship between the concentrations of bupivacaine and the reversal effects of 2% lipid emulsion. PMID:25089118

  9. Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants

    International Nuclear Information System (INIS)

    Poliandri, Ariel H.B.; Cabilla, Jimena P.; Velardez, Miguel O.; Bodo, Cristian C.A.; Duvilanski, Beatriz H.

    2003-01-01

    Cadmium (Cd 2+ ) is an ubiquitous toxic metal that is involved in a variety of pathological conditions. Several reports indicate that Cd 2+ alters normal pituitary hormone secretion; however, little is known about the mechanisms that induce this misregulation. This paper reports the effect of Cd 2+ on anterior pituitary cell viability and its relation to prolactin secretion. Cd 2+ concentrations above 10 μM were found to be cytotoxic for pituitary cells. Morphological studies as well as DNA ladder fragmentation and caspase activation showed that Cd 2+ -treated cells undergo apoptosis. Even though several hours were needed to detect Cd 2+ -induced cytotoxicity, the effect of the metal became irreversible very quickly, requiring only 3 h of treatment. Prolactin release (measured at 48 h) was inhibited when the cells were exposed to Cd 2+ for 1 h, before any change in cell viability was observed. The antioxidants N-acetyl-cysteine and Trolox (a hydrosoluble derivative of vitamin E), but not ascorbic acid, reversed both Cd 2+ -mediated cytotoxicity and the inhibition of prolactin release, supporting the involvement of oxidative stress in the mechanism of Cd 2+ action. In summary, the present work demonstrates that Cd 2+ is cytotoxic for anterior pituitary cells, that this effect is due to an induction of apoptosis, and that it can be reversed by antioxidants

  10. Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure.

    Science.gov (United States)

    Zhou, Xiaoming; Lu, Jordan Y-F; Darling, Ryan D; Simpson, Kimberly L; Zhu, Xiaoqing; Wang, Fang; Yu, Liping; Sun, Xinde; Merzenich, Michael M; Lin, Rick C S

    2015-02-17

    Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drug-exposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticity-based therapeutics in autistic patients.

  11. The effects of blood feeding and exogenous supply of tryptophan on the quantities of xanthurenic acid in the salivary glands of Anopheles stephensi (Diptera: Culicidae).

    Science.gov (United States)

    Okech, Bernard; Arai, Meiji; Matsuoka, Hiroyuki

    2006-03-24

    Xanthurenic acid (XA), produced as a byproduct during the biosynthesis of insect eye pigment (ommochromes), is a strong inducer of Plasmodium gametogenesis at very low concentrations. In previous studies, it was shown that XA is present in Anopheles stephensi (Diptera: Culicidae) mosquito salivary glands and that during blood feeding the mosquitoes ingested their own saliva into the midgut. Considering these two facts together, it is therefore likely that XA is discharged with saliva during blood feeding and is swallowed into the midgut where it exerts its effect on Plasmodium gametocytes. However, the quantities of XA in the salivary glands and midgut are unknown. In this study, we used high performance liquid chromatography with electrochemical detection to detect and quantify XA in the salivary glands and midgut. Based on the results of this study, we found 0.28+/-0.05 ng of XA in the salivary glands of the mosquitoes, accounting for 10% of the total XA content in the mosquito whole body. The amounts of XA in the salivary glands reduced to 0.13+/-0.06 ng after mosquitoes ingested a blood meal. Approximately 0.05+/-0.01 ng of XA was detected in the midgut of nonblood fed An. stephensi mosquitoes. By adding synthetic tryptophan as a source of XA into larval rearing water (2 mM) or in sugar meals (10 mM), we evaluated whether XA levels in the mosquito (salivary glands, midgut, and whole body) were boosted and the subsequent effect on infectivity of Plasmodium berghei in the treated mosquito groups. A female specific increase in XA content was observed in the whole body and in the midgut of mosquito groups where tryptophan was added either in the larval water or sugar meals. However, XA in the salivary glands was not affected by tryptophan addition to larval water, and surprisingly it reduced when tryptophan was added to sugar meals. The P. berghei oocyst loads in the mosquito midguts were lower in mosquitoes fed tryptophan treated sugar meals than in mosquitoes

  12. Reversal of chemotherapy-induced leukopenia using GM-CSF promotes bone metastasis that can be blocked with osteoclast inhibitors

    Science.gov (United States)

    Dai, Jinlu; Lu, Yi; Yu, Chunyan; Keller, Jill M.; Mizokami, Atsushi; Zhang, Jian; Keller, Evan T.

    2010-01-01

    Hematopoietic growth factors are used to reverse chemotherapy-induced leukopenia. However some factors such as GM-CSF induce osteoclast-mediated bone resorption that can promote cancer growth in bone. Accordingly, we evaluated the ability of GM-CSF to promote bone metastases of breast cancer (BrCa) or prostate cancer (PCa) in a mouse model of chemotherapy-induced leukopenia. In this model, GM-CSF reversed cyclophosphamide-induced leukopenia but also promoted BrCa and PCa growth in bone but not soft tissue sites. Bone growth was associated with induction of osteoclastogenesis, yet in the absence of tumor GM-CSF did not affect osteoclastogenesis. Two osteoclast inhibitors, the bisphosphonate zoledronic acid and the RANKL inhibitor OPG, each blocked GM-CSF-induced tumor growth in bone but did not reverse the ability of GM-CSF to reverse chemotherapy-induced leukopenia. Our findings indicate that it is possible to dissociate bone resorptive effects of GM-CSF, to reduce metastatic risk, from the benefits of this growth factor in reversing leukopenia caused by treatment with chemotherapy. PMID:20501834

  13. Injection-induced gluteus muscle contractures: diagnosis with the "reverse Ober test" and surgical management.

    Science.gov (United States)

    Scully, William F; White, Klane K; Song, Kit M; Mosca, Vincent S

    2015-03-01

    Adoption rates are increasing in the United States and other developed countries. A large proportion of adopted children have been found to have unsuspected medical diagnoses, including orthopedic problems. One condition, termed injection-induced gluteus maximus contracture, has been previously described in several case series and can be difficult to diagnose if unfamiliar with this condition. By reviewing the etiology and pathoanatomy of this problem, as well as the typical examination findings, including the near-pathognomonic-positive "reverse Ober test," treating providers will be better prepared to recognize and properly treat this condition. This is a retrospective review of 4 patients treated at our institution for injection-induced gluteus maximus contracture. Patient history, physical examination findings, and treatment outcomes were recorded. All had undergone surgical treatment through a longitudinal incision along the posterior margin of the iliotibial band, with division of thickened, contracted gluteus tissue down to the ischial tuberosity. All 4 of the patients were adopted from orphanages in developing countries. Chief complaints of the patients varied, but physical examination findings were very consistent. Three of the 4 patients had undergone rotational osteotomies for presumed femoral retroversion before their diagnosis and treatment for injection-induced gluteus maximus contracture. All patients had concave, atrophic buttock contours and numerous punctate buttock scars. All walked with an out-toed gait and had marked apparent femoral retroversion. Each patient was found to have full hip adduction when the hip was extended but a hip abduction contracture when the hip was flexed. This finding of increasing abduction as an extended/adducted hip is flexed to 90 degrees is described as a positive "reverse Ober test." After surgical treatment, all hips could adduct to neutral from full extension to full flexion. Although common in some countries

  14. The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

    Science.gov (United States)

    Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

    2007-12-01

    The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

  15. The effect of photoperiod on life history and blood-feeding activity in Aedes albopictus and Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Costanzo, K S; Schelble, S; Jerz, K; Keenan, M

    2015-06-01

    Several studies have examined how climatic variables such as temperature and precipitation may affect life history traits in mosquitoes that are important to disease transmission. Despite its importance as a seasonal cue in nature, studies investigating the influence of photoperiod on such traits are relatively few. This study aims to investigate how photoperiod alters life history traits, survival, and blood-feeding activity in Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus). We performed three experiments that tested the effects of day length on female survival, development time, adult size, fecundity, adult life span, and propensity to blood feed in Ae. albopictus and Ae. aegypti. Each experiment had three photoperiod treatments: 1) short-day (10L:14D), 2) control (12L:12D), and 3) long-day (14L:10D). Aedes albopictus adult females were consistently larger in size when reared in short-day conditions. Aedes aegypti adult females from short-day treatments lived longer and were more likely to take a blood meal compared to other treatments. We discuss how species-specific responses may reflect alternative strategies evolved to increase survival during unfavorable conditions. We review the potential impacts of these responses on seasonal transmission patterns, such as potentially increasing vectorial capacity of Ae. aegypti during periods of shorter day lengths. © 2015 The Society for Vector Ecology.

  16. Comparative Transcriptomic Analyses of Three Species of Placobdella (Rhynchobdellida: Glossiphoniidae) Confirms a Single Origin of Blood Feeding in Leeches.

    Science.gov (United States)

    Siddall, Mark E; Brugler, Mercer R; Kvist, Sebastian

    2016-02-01

    One of the recalcitrant questions regarding the evolutionary history of clitellate annelids involves the feeding preference of the common ancestor of extant rhynchobdellid (proboscis bearing) and arhynchobdellid (jaw bearing) leeches. Whereas early evidence, based on morphological data, pointed towards independent acquisitions of blood feeding in the 2 orders, molecular-based phylogenetic data suggest that the ancestor of modern leeches was a sanguivore. Here, we use a comparative transcriptomic approach in order to increase our understanding of the diversity of anticoagulation factors for 3 species of the genus Placobdella, for which comparative data have been lacking, and inspect these in light of archetypal anticoagulant data for both arhynchobdellid and other rhynchobdellid species. Notwithstanding the varying levels of host specificity displayed by the 3 different species of Placobdella, transcriptomic profiles with respect to anticoagulation factors were largely similar -this despite the fact that Placobdella kwetlumye only retains a single pair of salivary glands, as opposed to the 2 pairs more common in the genus. Results show that 9 different anticoagulant proteins and an additional 5 putative antihemostasis proteins are expressed in salivary secretions of the 3 species. In particular, an ortholog of the archetypal, single-copy, anticoagulant hirudin (not previously available as comparative data for rhynchobdellids) is present in at least 2 of 3 species examined, corroborating the notion of a single origin of blood feeding in the ancestral leech.

  17. [A clinical analysis of reninoma-induced hypertensive crisis associated with reversible posterior encephalopathy syndrome].

    Science.gov (United States)

    Wu, Hong-hua; Wang, Guang-ya; Ma, Xiao-wei; Guo, Xiao-hui

    2012-01-01

    Reninoma is a rare benign tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia via hypersecretion of renin, while it is extremely rare that reninoma induced hypertensive crisis with reversible posterior encephalopathy syndrome (RPES). To improve the clinical understanding for this disease, we conducted a case-analysis. To analyze the clinical and pathological data of a case of reninoma-induced hypertensive crisis with reversible posterior encephalopathy syndrome, who was admitted to Peking University First Hospital in November, 2007 and follow-up. This was a 16-year old female patient, onset with suddenly spasm with loss of consciousness, while blood pressure stepped up to 210/140 mm Hg (1 mm Hg = 0.133 kPa), and the head magnetic resonance imaging (MRI) revealed "multiple long-T(2) signal", and hypokalemia (2.8 - 3.2 mmol/L), urine protein positive, ultrasound cardiogram revealed left ventricular hypertrophy, laboratory study revealed hyperreninism (38.23 ng·ml(-1)×h(-1), normal range 0.07 - 1.15 ng·ml(-1)×h(-1)) and hyperaldosteronism (660.9 ng/L, normal range 60 - 174 ng/L), abdominal CT-Scan revealed a mass at right kidney, blood pressure achieved safety range and the head MRI was rechecked and revealed "the abnormal long-T(2) signal disappeared". The clinical diagnosis was reninoma induced hypertensive crisis with RPES. The tumor was resected and the pathologic diagnosis was reninoma. The patient remained normotensive in the postoperative period without any medication. Reninoma represents a rare but surgically curable cause of hypertension, thus the clinical suspicion of it is very important in young patients. If the diagnosis is confirmed, positive treatment must be done immediately to improve the prognosis. The most common cause of RPES is hypertension, and the diagnosis depends on the distinctive head MRI. There is always a good prognosis with the decline of blood pressure rapidly.

  18. Arbutus andrachne L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats.

    Science.gov (United States)

    Alzoubi, Karem H; Malkawi, Bayan S; Khabour, Omar F; El-Elimat, Tamam; Alali, Feras Q

    2018-02-01

    Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.

  19. Folate treatment partially reverses gestational low-protein diet-induced glucose intolerance and the magnitude of reversal is age and sex dependent.

    Science.gov (United States)

    Blesson, Chellakkan S; Schutt, Amy; Mathew, Pretty R; Tanchico, Daren; Balakrishnan, Meena; Yallampalli, Uma; Yallampalli, Chandra

    2017-11-13

    Gestational low-protein (LP) programming causes glucose intolerance (GI) and insulin resistance (IR) in adult offspring. Folate supplementation has been shown to rescue the offspring from various programming effects. The aim of this study was to investigate whether folate supplementation during pregnancy reverses LP-induced GI and IR. Pregnant rats were fed control (20% protein), isocaloric low-protein (LP, 6%) or LP with 5 mg/kg folate (LPF) diets from gestational day 4 to delivery. The control diet was given during lactation and to pups after weaning. Glucose tolerance test was done at 1, 2, and 3 mo of age followed by euglycemic-hyperinsulinemic clamp at 4 mo. Rats were sacrificed at 4 mo and their gonadal, renal, inguinal, brown fat, and pancreas were weighed and expressed relative to their body weight. LP- and LPF-fed dams showed similar weight loss during late pregnancy after decreased feed intake. Both LP and LPF pups were smaller at birth but their weights caught up like that of controls by 3 mo. In males, folate supplementation reduced LP-induced GI at 2 mo (glucose area under the curve [AUC]: 1940 mmol/L × 180 min in LP, 1629 mmol/L × 180 min in LPF, and 1653 mmol/L × 180 min in controls; P reverses LP-induced GI and the magnitude of reversal is age and sex dependent. Furthermore, folate treatment does not reverse IR in either sex but makes it worse in males at 4 mo. The present study demonstrated that folate treatment is not sufficient to rescue the LP programming effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Morphological analysis of human induced pluripotent stem cells during induced differentiation and reverse programming.

    Science.gov (United States)

    Courtot, Anne-Marie; Magniez, Aurélie; Oudrhiri, Noufissa; Féraud, Olivier; Bacci, Josette; Gobbo, Emilie; Proust, Stéphanie; Turhan, Ali G; Bennaceur-Griscelli, Annelise

    2014-10-01

    The fine analysis of cell components during the generation of pluripotent cells and their comparison to bone fide human embryonic stem cells (hESCs) are valuable tools to understand their biological behavior. In this report, human mesenchymal cells (hMSCs) generated from the human ES cell line H9, were reprogrammed back to induced pluripotent state using Oct-4, Sox2, Nanog, and Lin28 transgenes. Human induced pluripotent stem cells (hIPSCs) were analyzed using electron microscopy and compared with regard to the original hESCs and the hMSCs from which they were derived. This analysis shows that hIPSCs and the original hESCs are morphologically undistinguishable but differ from the hMSCs with respect to the presence of several morphological features of undifferentiated cells at both the cytoplasmic (ribosomes, lipid droplets, glycogen, scarce reticulum) and nuclear levels (features of nuclear plasticity, presence of euchromatin, reticulated nucleoli). We show that hIPSC colonies generated this way presented epithelial aspects with specialized junctions highlighting morphological criteria of the mesenchymal-epithelial transition in cells engaged in a successful reprogramming process. Electron microscopic analysis revealed also specific morphological aspects of partially reprogrammed cells. These results highlight the valuable use of electron microscopy for a better knowledge of the morphological aspects of IPSC and cellular reprogramming.

  1. Reversal of succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase.

    Directory of Open Access Journals (Sweden)

    Brian C Geyer

    Full Text Available Concerns about the safety of paralytics such as succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for succinylcholine hydrolysis, are susceptible to succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of succinylcholine.Recombinant butyrylcholinesterase was produced in transgenic plants and purified. Further analysis involved murine and guinea pig models of succinylcholine toxicity. Animals were treated with lethal and sublethal doses of succinylcholine followed by administration of butyrylcholinesterase or vehicle. In both animal models vital signs and overall survival at specified intervals post succinylcholine administration were assessed.Purified plant-derived recombinant human butyrylcholinesterase can hydrolyze succinylcholine in vitro. Challenge of mice with an LD100 of succinylcholine followed by BChE administration resulted in complete prevention of respiratory inhibition and concomitant mortality. Furthermore, experiments in symptomatic guinea pigs demonstrated extremely rapid succinylcholine detoxification with complete amelioration of symptoms and no apparent complications.Recombinant plant-derived butyrylcholinesterase was capable of counteracting and reversing apnea in two complementary models of lethal succinylcholine toxicity, completely preventing mortality. This study of a protein antidote validates the feasibility

  2. Photobiostimulation reverses allodynia and peripheral nerve damage in streptozotocin-induced type 1 diabetes.

    Science.gov (United States)

    Rocha, Igor Rafael Correia; Ciena, Adriano Polican; Rosa, Alyne Santana; Martins, Daniel Oliveira; Chacur, Marucia

    2017-04-01

    For better evaluation of the efficacy of low-level laser therapy in treating painful diabetic neuropathy and in protecting nerve fiber damage, we conducted a study with type 1 diabetic rats induced by streptozotocin. It is well known that diabetic peripheral neuropathy is the leading cause of pain in those individuals who suffer from diabetes. Despite the efficacy of insulin in controlling glucose level in blood, there is no effective treatment to prevent or reverse neuropathic damage for total pain relief.Male Wistar rats were divided into saline, vehicle, and treatment groups. A single intraperitoneal (i.p.) injection of streptozotocin (STZ) (85 mg/kg) was administered for the induction of diabetes. The von Frey filaments were used to assess nociceptive thresholds (allodynia). Behavioral measurements were accessed 14, 28, 48, and 56 days after STZ administration. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm 2 , a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm 2 .The application of four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.The results of this study indicate that low-level laser therapy is feasible to treat painful diabetic condition in rats using this protocol. Although its efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

  3. Reversible Heat-Induced Inactivation of Chimeric β-Glucuronidase in Transgenic Plants1

    Science.gov (United States)

    Almoguera, Concepción; Rojas, Anabel; Jordano, Juan

    2002-01-01

    We compared the expression patterns in transgenic tobacco (Nicotiana tabacum) of two chimeric genes: a translational fusion to β-glucuronidase (GUS) and a transcriptional fusion, both with the same promoter and 5′-flanking sequences of Ha hsp17.7 G4, a small heat shock protein (sHSP) gene from sunflower (Helianthus annuus). We found that immediately after heat shock, the induced expression from the two fusions in seedlings was similar, considering chimeric mRNA or GUS protein accumulation. Surprisingly, we discovered that the chimeric GUS protein encoded by the translational fusion was mostly inactive in such conditions. We also found that this inactivation was fully reversible. Thus, after returning to control temperature, the GUS activity was fully recovered without substantial changes in GUS protein accumulation. In contrast, we did not find differences in the in vitro heat inactivation of the respective GUS proteins. Insolubilization of the chimeric GUS protein correlated with its inactivation, as indicated by immunoprecipitation analyses. The inclusion in another chimeric gene of the 21 amino-terminal amino acids from a different sHSP lead to a comparable reversible inactivation. That effect not only illustrates unexpected post-translational problems, but may also point to sequences involved in interactions specific to sHSPs and in vivo heat stress conditions. PMID:12011363

  4. Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition

    Science.gov (United States)

    Tian, Xiao-Jun; Zhang, Hang; Xing, Jianhua

    2013-01-01

    Epithelial to mesenchymal transition (EMT) plays an important role in embryonic development, tissue regeneration, and cancer metastasis. Whereas several feedback loops have been shown to regulate EMT, it remains elusive how they coordinately modulate EMT response to TGF-β treatment. We construct a mathematical model for the core regulatory network controlling TGF-β-induced EMT. Through deterministic analyses and stochastic simulations, we show that EMT is a sequential two-step program in which an epithelial cell first is converted to partial EMT then to the mesenchymal state, depending on the strength and duration of TGF-β stimulation. Mechanistically the system is governed by coupled reversible and irreversible bistable switches. The SNAIL1/miR-34 double-negative feedback loop is responsible for the reversible switch and regulates the initiation of EMT, whereas the ZEB/miR-200 feedback loop is accountable for the irreversible switch and controls the establishment of the mesenchymal state. Furthermore, an autocrine TGF-β/miR-200 feedback loop makes the second switch irreversible, modulating the maintenance of EMT. Such coupled bistable switches are robust to parameter variation and molecular noise. We provide a mechanistic explanation on multiple experimental observations. The model makes several explicit predictions on hysteretic dynamic behaviors, system response to pulsed stimulation, and various perturbations, which can be straightforwardly tested. PMID:23972859

  5. Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rutian Li

    Full Text Available AIMS: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs are able to overcome this "pH-induced physiological drug resistance" (PIPDR by delivering drugs to the cancer cells via endocytosis rather than passive diffussion. MATERIALS AND METHODS: As a model nanoparticle, Tetradrine (Tet, Pka 7.80 was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo. RESULTS: The cytotoxicity of free Tet decreased prominently (P<0.05 when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects. CONCLUSION: The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect.

  6. Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion.

    Science.gov (United States)

    Vaidyanathan, Sriram; Williamson, Peter; Clearie, Karine; Khan, Faisel; Lipworth, Brian

    2010-07-01

    Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by alpha-adrenoceptor mediated down-regulation and desensitization of response. We evaluated if tachyphylaxis can be reversed by intranasal fluticasone propionate, and the relative alpha(1)- and alpha(2)-adrenoceptor components of tachyphylaxis using the alpha(1)-antagonist prazosin. In a randomized, double-blind, placebo-controlled, crossover design, 19 healthy subjects received intranasal oxymetazoline, 200 microg three times a day for 14 days, followed by the addition of fluticasone, 200 microg twice a day for a further 3 days. At Days 1, 14, and 17, participants received a single dose of oral prazosin, 1 mg, or placebo with measurements made before and 2 hours later. Outcomes evaluated were peak nasal inspiratory flow, nasal resistance, blood flow, and oxymetazoline dose-response curve (DRC). On Day 14 versus Day 1, inspiratory flow decreased (mean difference, 95% confidence interval) (-47.9 L x min(-1); -63.9 to -31.9; P Oxymetazoline-induced tachyphylaxis and rebound congestion are reversed by intranasal fluticasone. Further studies are indicated to evaluate if combination nasal sprays of decongestant and corticosteroid are an effective strategy to obviate tachyphylaxis and rebound in rhinitis. Clinical trial registered with www.clinicaltrials.gov (NCT 00487032).

  7. Augmented Hebbian reweighting accounts for accuracy and induced bias in perceptual learning with reverse feedback

    Science.gov (United States)

    Liu, Jiajuan; Dosher, Barbara Anne; Lu, Zhong-Lin

    2015-01-01

    Using an asymmetrical set of vernier stimuli (−15″, −10″, −5″, +10″, +15″) together with reverse feedback on the small subthreshold offset stimulus (−5″) induces response bias in performance (Aberg & Herzog, 2012; Herzog, Eward, Hermens, & Fahle, 2006; Herzog & Fahle, 1999). These conditions are of interest for testing models of perceptual learning because the world does not always present balanced stimulus frequencies or accurate feedback. Here we provide a comprehensive model for the complex set of asymmetric training results using the augmented Hebbian reweighting model (Liu, Dosher, & Lu, 2014; Petrov, Dosher, & Lu, 2005, 2006) and the multilocation integrated reweighting theory (Dosher, Jeter, Liu, & Lu, 2013). The augmented Hebbian learning algorithm incorporates trial-by-trial feedback, when present, as another input to the decision unit and uses the observer's internal response to update the weights otherwise; block feedback alters the weights on bias correction (Liu et al., 2014). Asymmetric training with reversed feedback incorporates biases into the weights between representation and decision. The model correctly predicts the basic induction effect, its dependence on trial-by-trial feedback, and the specificity of bias to stimulus orientation and spatial location, extending the range of augmented Hebbian reweighting accounts of perceptual learning. PMID:26418382

  8. Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

    Science.gov (United States)

    Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

    2017-08-01

    Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

  9. A reversible strain-induced electrical conductivity in cup-stacked carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, T [Shinshu University; Morokuma, Keiji [ORNL; Meunier, Vincent [ORNL; Meunier, V. [Rensselaer Polytechnic Institute (RPI); Terrones Maldonado, Mauricio [ORNL; Muramatsu, H [Shinshu University; Sumpter, Bobby G [ORNL; Kim, Y A [Shinshu University

    2013-01-01

    We have used in-situ current-voltage measurements of cup-stacked carbon nanotubes (CSCNTs) to establish a reversible strain induced (compressive bending) semiconducting to metallic behavior. The corresponding electrical resistance decreases by two orders of magnitude during the process, and reaches values comparable to those of highly crystalline multi-walled carbon nanotube (MWCNT) and graphite. Joule heating experiments on the same CSCNTs showed that the edges of individual cups merge to form loops induced by the heating process. The resistance of these looped CSCNTs was close to that of highly deformed CSCNTs (and crystalline MWCNTs), thus suggesting that a similar conduction mechanism took place in both cases. Using a combination of molecular dynamics and first-principles calculations based on density functional theory, we conclude that an edge-to-edge interlayer transport mechanism results in conduction channels at the compressed side of the CSCNTs due to electronic density overlap between individual cups, thus making CSCNT more conducting. This strain-induced CSCNT semiconductor to metal transition could potentially be applied to enabling functional composite materials (e.g. mechanical sensors) with enhanced and tunable conducting properties upon compression.

  10. Sodium butyrate reverses the inhibition of Krebs cycle enzymes induced by amphetamine in the rat brain.

    Science.gov (United States)

    Valvassori, Samira S; Calixto, Karen V; Budni, Josiane; Resende, Wilson R; Varela, Roger B; de Freitas, Karolina V; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2013-12-01

    There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.

  11. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress.

    Science.gov (United States)

    van der Harg, J M; Nölle, A; Zwart, R; Boerema, A S; van Haastert, E S; Strijkstra, A M; Hoozemans, J Jm; Scheper, W

    2014-08-28

    The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) in close connection with early stages of tau pathology. Metabolic disturbances are strongly associated with increased risk for AD and are a potent inducer of the UPR. Here, we demonstrate that metabolic stress induces the phosphorylation of endogenous tau via activation of the UPR. Strikingly, upon restoration of the metabolic homeostasis, not only the levels of the UPR markers pPERK, pIRE1α and BiP, but also tau phosphorylation are reversed both in cell models as well as in torpor, a physiological hypometabolic model in vivo. Intervention in the UPR using the global UPR inhibitor TUDCA or a specific small-molecule inhibitor of the PERK signaling pathway, inhibits the metabolic stress-induced phosphorylation of tau. These data support a role for UPR-mediated tau phosphorylation as part of an adaptive response to metabolic stress. Failure to restore the metabolic homeostasis will lead to prolonged UPR activation and tau phosphorylation, and may thus contribute to AD pathogenesis. We demonstrate that the UPR is functionally involved in the early stages of tau pathology. Our data indicate that targeting of the UPR may be employed for early intervention in tau-related neurodegenerative diseases.

  12. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  13. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

    DEFF Research Database (Denmark)

    Wu, Guoxin; Swanson, Michael; Talla, Aarthi

    2017-01-01

    Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions......, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein...... induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3...

  14. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark

    2015-01-01

    ] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. IMPORTANCE: Commonly, antibiotic resistance......UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...... is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistant...

  15. Strategies for reversing the effects of metabolic disorders induced as a consequence of developmental programming

    Directory of Open Access Journals (Sweden)

    Mark H Vickers

    2012-07-01

    Full Text Available Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioural influences, rather than genetic causes, are fuelling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment.

  16. A joined role of canopy and reversal cells in bone remodeling - Lessons from glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe

    2015-01-01

    - and glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e. uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces....... In postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis...... biopsies, and their prevalence correlated with a deficiency in bone forming surfaces. Taken together with the other recent data, the functional link between canopies, reversal surface activity, and the extent of bone formation surface in postmenopausal- and glucocorticoid-induced osteoporosis, supports...

  17. Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway

    Directory of Open Access Journals (Sweden)

    Lin H

    2014-07-01

    Full Text Available Hao Lin,1,* Bo Wei,1,* Guangsheng Li,1 Jinchang Zheng,1 Jiecong Sun,1 Jiaqi Chu,2 Rong Zeng,1 Yanru Niu21Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China; 2Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs has been identified as a major cause of osteoporosis. However, the underlying molecular mechanisms accounting for this action remain elusive, which has impeded the prevention and cure of this side effect. Sulforaphane (SFP is a naturally occurring isothiocyanate that has huge health benefits for humans. In this study, by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective effects of SFP against dexamethasone (Dex-induced apoptosis and elucidate the underlying molecular mechanisms. The results show that SFP could effectively inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3-E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin condensation, and deoxyribonucleic acid fragmentation, which were significantly suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway contributed importantly to Dex-induced apoptosis, as revealed by the activation of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose polymerase, which was also effectively blocked by SFP. Moreover, treatments of Dex strongly induced overproduction of reactive oxygen species and inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and the downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively reversed this action of Dex. Furthermore, silencing of Nrf2 by

  18. D-cycloserine in prelimbic cortex reverses scopolamine-induced deficits in olfactory memory in rats.

    Directory of Open Access Journals (Sweden)

    Marta Portero-Tresserra

    Full Text Available A significant interaction between N-methyl-D-aspartate (NMDA and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS, a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC. Thus, in experiment 1, DCS (10 µg/site was infused prior to acquisition of odor discrimination (ODT and social transmission of food preference (STFP, which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site and the effects of both drugs (alone and combined were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1 or a more challenging three-choice test (experiment 2. The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks.

  19. Apomorphine-induced hypoattention in rats and reversal of the choice performance impairment by aniracetam.

    Science.gov (United States)

    Nakamura, K; Kurasawa, M; Tanaka, Y

    1998-01-26

    Aging-, disease- and medication-related imbalance of central dopaminergic neurons causes functional impairment of cognition and neuropsychological delirium in humans. We attempted to develop a new delirium model using the direct dopamine agonist, apomorphine, and a choice reaction performance task performed by middle-aged rats. The psychological properties of the model were assessed by determining behavioral measures such as choice reaction time, % correct and % omission. Apomorphine (0.03-0.3 mg/kg s.c.) produced a dose-dependent impairment of task performance. The dose of 0.1 mg/kg prolonged choice reaction time, decreased % correct and increased % omission, indicating that rats had attentional deficits and a reduced arousal or vigilance but no motor deficits or reduced food motivation. This psychological and behavioral impairment of performance resembled that of clinically defined delirium. In this model, the cholinomimetic, aniracetam (10 mg/kg p.o.), reversed the performance impairment induced by apomorphine. Its two metabolites, 2-pyrrolidinone (10 and 30 mg/kg p.o.) and N-anisoyl-gamma-aminobutyric acid (GABA, 10 mg/kg p.o.), effectively reversed the performance impairment as the intact drug did. Another pyrrolidinone derivative, nefiracetam (10 and 30 mg/kg p.o.), tended to worsen the apomorphine effect. The cholinesterase inhibitor, tacrine (10 mg/kg p.o.), markedly worsened all of the behavioral measures. Neuroleptics, haloperidol (0.025 mg/kg s.c.), tiapride (30 mg/kg p.o.) and sulpiride (10 and 30 mg/kg p.o.), antagonized the apomorphine effect. The present results suggest that apomorphine-induced behavioral disturbances in the choice reaction performance task seems to be a useful delirium model and aniracetam may improve delirium through the action of 2-pyrrolidinone and N-anisoyl-GABA, presumably by facilitating dopamine release in the striatum by acting as an AMPA or metabotropic glutamate receptor agonist.

  20. Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

    Science.gov (United States)

    Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi

    2017-03-01

    Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular

  1. Ginsenoside Rh2 reverses sleep deprivation-induced cognitive deficit in mice.

    Science.gov (United States)

    Lu, Cong; Wang, Yan; Lv, Jingwei; Jiang, Ning; Fan, Bei; Qu, Lina; Li, Yinghui; Chen, Shanguang; Wang, Fengzhong; Liu, Xinmin

    2018-03-12

    Sleep deprivation (SD) negatively caused cognitive deficit, which was associated with oxidative stress induced damage. Ginsenoside Rh2 had the ability to protect against damage caused by reactive oxygen species in vitro, showing antioxidant property. Therefore, it was hypothesized that Ginsenoside Rh2 could prevent SD-induced cognitive deficit via its antioxidant properties. In this study, the effect of Ginsenoside Rh2 on memory impairment induced by sleep deprivation was investigated. The mice were sleep deprived continuously for 14 days using our self-made Sleep Interruption Apparatus (SIA). Ginsenoside Rh2 was administered intraperitoneally at two doses (20 and 40 μmol/kg) for 20 days. Thereafter, behavioral studies were conducted to test the learning and memory ability using object location recognition (OLR) experiment and passive avoidance (PA) test. Additionally, the oxidative stress parameters in the serum and the brain tissues (cortex and hippocampus) were assessed, including the superoxide dismutase (SOD) enzyme activity, the total antioxidant reactivity (TAR), the malondialdehyde (MDA) level, the glutathione (GSH) level, and the lipid peroxidation (LPO) content. The results revealed that SD impaired both spatial and non-spatial memory (P memory impairment induced by SD. Moreover, Ginsenoside Rh2 normalized the reduction of SOD and TAR activities in the serum (P sleep deprivation impaired both spatial and non-spatial memory and Ginsenoside Rh2 reversed this impairment, probably by preventing the oxidative stress damage in the body, including the serum and brain during sleep deprivation. Copyright © 2018. Published by Elsevier B.V.

  2. Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

    LENUS (Irish Health Repository)

    Li, Chong Hui

    2012-03-01

    Tolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and\\/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.

  3. Effects of in vivo exposure to DEET on blood feeding behavior and fecundity in Anopheles quadrimaculatus (Diptera: Culicidae).

    Science.gov (United States)

    Xue, Rui-De; Ali, Arshad; Barnard, Donald R

    2007-07-01

    This study determined the effects of contact with DEET on guinea pig skin on mortality, probing time, blood feeding rate, engorgement time, and fecundity responses in female Anopheles quadrimaculatus Say. Exposure, in this manner, to 10% DEET (in ethanol) for 5 min, resulted in 98% mortality in mosquitoes after 24h. The median probing time (PT(50)) required by females, when exposed to 0.1%, 1.0%, and 10% DEET, was significantly (Pblood feeding rates in populations of females exposed to 1.0% DEET for feeding on the control guinea pigs (105.9s). The mean number of mature oöcytes per female (fecundity) in treatment (1.0% DEET) and control mosquitoes was not significantly different. The responses to DEET observed in this study suggest that repeated exposure of female A. quadrimaculatus populations to this repellent, in laboratory bioassays, could result in confounding of toxicant and repellent effects and inaccurate estimates of DEET repellency.

  4. Expression of telomerase reverse transcriptase in radiation-induced chronic human skin ulcer

    International Nuclear Information System (INIS)

    Zhao Po; Li Zhijun; Lu Yali; Zhong Mei; Gu Qingyang; Wang Dewen

    2001-01-01

    Objective: To investigate the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase (TRT) and the possible relationship between the TRT and cancer transformation or poor healing in radiation-induced chronic ulcer of human skin. Methods: Rabbit antibody against human TRT and SP immunohistochemical method were used to detect TRT expression in 24 cases of formalin-fixed, paraffin-embed human skin chronic ulcer tissues induced by radiation, 5 cases of normal skin, 2 of burned skin, and 8 of carcinoma. Results: The positive rate for TRT was 58.3%(14/24) in chronic radiation ulcers, of which the strongly positive rate was 41.7%(10/24) and the weakly positive 16.7%(4/24), 0% in normal (0/5) and burned skin (0/2), and 100% in carcinoma (8/8). The strongly positive expression of TRT was observed almost always in the cytoplasm and nucleus of squamous epithelial cells of proliferative epidermis but the negative and partly weakly positive expression in the smooth muscles, endothelia of small blood vessels and capillaries, and fibroblasts. Chronic inflammtory cells, plasmacytes and lymphocytes also showed weakly positive for TRT. Conclusion: TRT expression could be involved in the malignant transformation of chronic radiation ulcer into squamous carcinoma, and in the poor healing caused by sclerosis of small blood vessels and lack of granulation tissue consisting of capillaries and fibroblasts

  5. Simulated Seasonal Photoperiods and Fluctuating Temperatures Have Limited Effects on Blood Feeding and Life History in Aedes triseriatus (Diptera: Culicidae).

    Science.gov (United States)

    Westby, K M; Juliano, S A

    2015-09-01

    Biotic and abiotic factors change seasonally and impact life history in temperate-zone ectotherms. Temperature and photoperiod are factors that change in predictable ways. Most studies testing for effects of temperature on vectors use constant temperatures and ignore potential correlated effects of photoperiod. In two experiments, we tested for effects of larval rearing environments creating ecologically relevant temperatures and photoperiods simulating early and late season conditions (June and August), or constant temperatures (cool and warm) with the June or August photoperiods, respectively. We determined effects on survivorship, development, size, and a composite performance index in a temperate-zone population of Aedes triseriatus (Say). We followed cohorts of resulting females, all held under the same environmental conditions, to assess carry-over effects of rearing conditions for larvae on longevity, blood feeding, and egg production. Larval survivorship was affected by treatment in one experiment. Development time was greater in the June and cool treatments, but the constant and fluctuating temperatures did not differ. Significantly larger mosquitoes were produced in fluctuating versus constant temperature treatments. There were no significant treatment effects on the composite performance index. Adult female longevity was lower after rearing at constant versus fluctuating temperature, but there was no difference between June and August, nor did size affect longevity. There was no effect of treatments on blood feeding and a limited effect on egg production. We conclude that seasonal temperatures and photoperiods during development have limited effects on this population of A. triseriatus and find little evidence of strong effects of fluctuating versus constant temperatures. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

    Science.gov (United States)

    Lytle, Kelli A; Jump, Donald B

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.e., low fat diets and weight loss) is imperative. We evaluated the efficacy of two diets, a non-purified chow (NP) and purified (low-fat low-cholesterol, LFLC) diet to reverse western diet (WD)-induced NASH and fibrosis in Ldlr-/- mice. Mice fed WD for 22-24 weeks developed robust hepatosteatosis with mild fibrosis, while mice maintained on the WD an additional 7-8 weeks developed NASH with moderate fibrosis. Returning WD-fed mice to the NP or LFLC diets significantly reduced body weight and plasma markers of metabolic syndrome (dyslipidemia, hyperglycemia) and hepatic gene expression markers of inflammation (Mcp1), oxidative stress (Nox2), fibrosis (Col1A, LoxL2, Timp1) and collagen crosslinking (hydroxyproline). Time course analyses established that plasma triglycerides and hepatic Col1A1 mRNA were rapidly reduced following the switch from the WD to the LFLC diet. However, hepatic triglyceride content and fibrosis did not return to normal levels 8 weeks after the change to the LFLC diet. Time course studies further revealed a strong association (r2 ≥ 0.52) between plasma markers of inflammation (TLR2 activators) and hepatic fibrosis markers (Col1A, Timp1, LoxL2). Inflammation and fibrosis markers were inversely associated (r2 ≥ 0.32) with diet-induced changes in hepatic ω3 and ω6 polyunsaturated fatty acids (PUFA) content. These studies establish a temporal link between plasma markers of inflammation and hepatic PUFA and fibrosis. Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD-induced NASH and fibrosis in Ldlr-/- mice.

  7. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

    International Nuclear Information System (INIS)

    Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte; Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina

    2006-01-01

    Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [ 11 C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

  8. Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau

    Science.gov (United States)

    Sydow, Astrid; Hofmann, Anne; Wu, Dan; Messing, Lars; Balschun, Detlef; D'Hooge, Rudi; Mandelkow, Eva-Maria

    2016-01-01

    Neurofibrillary lesions of abnormal Tau are hallmarks of Alzheimer´s disease and frontotemporal dementias. Our regulatable (Tet-OFF) mouse models of tauopathy express variants of human full-length Tau in the forebrain (CaMKIIα promoter) either with mutation ΔK280 (pro-aggregant) or ΔK280/I277P/I308P (anti-aggregant). Co-expression of luciferase enables in vivo quantification of gene expression by bioluminescence imaging. Pro-aggregant mice develop synapse loss and Tau pathology including missorting, phosphorylation and early pretangle formation, whereas anti-aggregant mice do not. We correlated hippocampal Tau pathology with learning/memory performance and synaptic plasticity. Pro-aggregant mice at 16 months of gene expression exhibited severe cognitive deficits in Morris water-maze and in passive-avoidance paradigms, whereas anti-aggregant mice were comparable to controls. Cognitive impairment of pro-aggregant mice was accompanied by loss of hippocampal LTP in CA1 and CA3 areas and by a reduction of synaptic proteins and dendritic spines, although no neuronal loss was observed. Remarkably, memory and LTP recovered when pro-aggregant Tau was switched-OFF for ∼4 months, Tau phosphorylation and missorting were reversed, and synapses recovered. Moreover soluble and insoluble pro-aggregant hTau40 disappeared while insoluble mouse Tau was still present. This study links early Tau pathology without neurofibrillary tangles and neuronal death to cognitive decline and synaptic dysfunction. It demonstrates that Tau-induced impairments are reversible after switching-OFF pro-aggregant Tau. Therefore our mouse model may mimic an early phase of AD when the hippocampus does not yet suffer from irreversible cell death but cognitive deficits are already striking. It offers potential to evaluate drugs with regard to learning and memory performance. PMID:22532069

  9. Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

    Science.gov (United States)

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

    2016-09-15

    Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

    Directory of Open Access Journals (Sweden)

    Shilpa Bhimasen Joshi

    2015-01-01

    Full Text Available Background and Aims: Obese patients are more vulnerable to residual neuromuscular block (NMB and its associated complications in the post-operative period. This study was carried out to compare neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients, objectively using neuromuscular (NM monitoring. Methods: Twenty female patients each belonging to normal weight, overweight and obese, based on body mass index, requiring general anaesthesia were recruited for this prospective cross sectional study. NMB was induced with vecuronium (0.1 mg/kg dose based on patient′s real body weight (RBW and monitored using acceleromyographic train of four (TOF. All patients received neostigmine 40 μg/kg and glycopyrrolate 10 μg/kg at 25% of spontaneous recovery of first twitch height (T1 of TOF (DUR 25% and were allowed to recover to TOF ratio of 0.9. Statistical analysis was done using analysis of variance test. Results: Recovery of TOF ratio to 0.5 was comparable in all three groups. Recovery of TOF ratio to 0.7 was delayed in obese (9.82 ± 3.21 min compared with normal weight group (7.50 ± 2.52 min. Recovery of TOF to 0.9 was significantly delayed in both overweight (12.18 ± 4.29 min and obese patients (13.78 ± 4.30 min. DUR 25% was significantly longer in overweight (mean, standard deviation [range]; 30.10 [19-40 min] and obese (28.8 [12-45 min] compared with normal weight patients (22.75 [16-30 min]. Conclusion: In overweight and obese patients, when vecuronium induction dose is based on RBW, neostigmine induced recovery of NMB is delayed in late phases (TOF 0.7-0.9, which may result in vulnerability for associated complications of incomplete recovery. Ensuring safe recovery thus requires objective NM monitoring.

  11. Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity

    Science.gov (United States)

    Hamelink, Carol; Hampson, Aidan; Wink, David A.; Eiden, Lee E.; Eskay, Robert L.

    2014-01-01

    Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-D-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and α-tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury. PMID:15878999

  12. Electric field-induced magnetization reversal in a perpendicular-anisotropy CoFeB-MgO magnetic tunnel junction

    Science.gov (United States)

    Kanai, S.; Yamanouchi, M.; Ikeda, S.; Nakatani, Y.; Matsukura, F.; Ohno, H.

    2012-09-01

    The electric field-induced ˜180° magnetization reversal is realized for a sputtered CoFeB/MgO-based magnetic tunnel junction with perpendicular magnetic easy axis in a static external magnetic field. Application of bias voltage with nanoseconds duration results in a temporal change of magnetic easy axis in the free layer CoFeB to in-plane, which induces precessional motion of magnetization in the free layer. The magnetization reversal takes place when the bias voltage pulse duration is adjusted to a half period of the precession. We show that the back and forth magnetization reversal can be observed by using successive application of half-period voltage pulses.

  13. Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo

    2014-01-01

    Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy and s...

  14. Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α.

    Science.gov (United States)

    Qian, Jiang; Shen, Sheliang; Chen, Wei; Chen, Nianping

    2018-01-01

    Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial-mesenchymal transition (EMT), driven by hypoxia-inducible factor 1 α (HIF-1 α ), is involved in cancer progression and metastasis. The present study was designed to explore the role of propofol in hypoxia-induced resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assay to measure cell viability and cell proliferation, respectively, in prostate cancer cell lines. Then, we detected HIF-1 α , E-cadherin, and vimentin expression using western blotting. Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer cell lines. Propofol not only decreased hypoxia-induced HIF-1 α expression, but also reversed hypoxia-induced EMT by suppressing HIF-1 α . Furthermore, small interfering RNA-mediated silencing of HIF-1 α reversed the hypoxia-induced docetaxel resistance, although there was little change in docetaxel sensitivity between the hypoxia group and propofol group. The induction of hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA knockdown conditions, the effects of propofol were obviated. These data support a role for propofol in regulating EMT in prostate cancer cells. Taken together, our findings demonstrate that propofol plays an important role in hypoxia-induced docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential drug for overcoming drug resistance in prostate cancer cells via HIF-1 α suppression.

  15. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

    Directory of Open Access Journals (Sweden)

    Sun Woo Sophie Kang

    Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

  16. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

    Science.gov (United States)

    Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

    2016-01-01

    Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

  17. Depressive-like phenotype induced by prenatal dexamethasone in mice is reversed by desipramine.

    Science.gov (United States)

    Conti, Mirko; Spulber, Stefan; Raciti, Marilena; Ceccatelli, Sandra

    2017-11-01

    Exposure to prenatal insults has been associated with an increased risk for neuropsychiatric disorders, including depression, but the mechanisms are still poorly understood. Persistent alterations of the HPA axis feedback mechanism as well as adult impaired neurogenesis are believed to play a relevant role in the etiology of depression. In addition, growing evidence points at epigenetic reprogramming as a key factor. We have previously shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) impairs neurogenesis and leads to late onset of depression-like behavior that does not respond to the SSRI antidepressant fluoxetine (FLX). The aims of this study were to assess the effect of DEX prenatal exposure on the morphology of hippocampal granule neurons and on the expression of genes related to plasticity; and to test whether the SNRI antidepressant desipramine (DMI), unlike FLX, could counteract the effect of prenatal-DEX. C57Bl/6 mice were exposed to DEX (0.05 mg/kg/day) in utero and received intra-hippocampal injection of GFP expressing retroviral vector for labeling of newborn granule cells at eleven months. By twelve months, DEX mice showed depression-like behavior associated with decreased neurogenesis and morphological alterations of the newborn granule cells in the dentate gyrus (DG). Furthermore DEX mice displayed altered expression of genes controlling neurogenesis and neuronal morphology, such as Cdkn1c, p16, TrkB, DISC1 and Reelin. Chronic treatment with DMI led to a significant decrease in immobility time in the forced swim test. In addition, DMI restored neurogenesis, neuronal morphology in the DG, as well as the expression of all related genes. Our results suggest that (1) prenatal DEX induces early and persistent reprogramming effects resulting in altered neurogenesis and neuronal morphology; and (2) DMI treatment reverses DEX-induced depression by restoring the expression of genes relevant to neuronal plasticity. Copyright

  18. Reverse feeding suppresses the activity of the GH axis in rats and induces a preobesogenic state.

    Science.gov (United States)

    Glad, Camilla A-M; Kitchen, Edward E J; Russ, Gemma C; Harris, Sophie M; Davies, Jeffrey S; Gevers, Evelien F; Gabrielsson, Britt G; Wells, Timothy

    2011-03-01

    Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.

  19. Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Kang, E.; Jung, J.W.

    2015-01-01

    A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

  20. Localization of Reversion-Induced LIM Protein (RIL) in the Rat Central Nervous System

    International Nuclear Information System (INIS)

    Iida, Yuko; Matsuzaki, Toshiyuki; Morishima, Tetsuro; Sasano, Hiroshi; Asai, Kiyofumi; Sobue, Kazuya; Takata, Kuniaki

    2009-01-01

    Reversion-induced LIM protein (RIL) is a member of the ALP (actinin-associated LIM protein) subfamily of the PDZ/LIM protein family. RIL serves as an adaptor protein and seems to regulate cytoskeletons. Immunoblotting suggested that RIL is concentrated in the astrocytes in the central nervous system. We then examined the expression and localization of RIL in the rat central nervous system and compared it with that of water channel aquaporin 4 (AQP4). RIL was concentrated in the cells of ependyma lining the ventricles in the brain and the central canal in the spinal cord. In most parts of the central nervous system, RIL was expressed in the astrocytes that expressed AQP4. Double-labeling studies showed that RIL was concentrated in the cytoplasm of astrocytes where glial fibrillary acidic protein was enriched as well as in the AQP4-enriched regions such as the endfeet or glia limitans. RIL was also present in some neurons such as Purkinje cells in the cerebellum and some neurons in the brain stem. Differential expression of RIL suggests that it may be involved in the regulation of the central nervous system

  1. Pressure-induced reversal between thermal contraction and expansion in ferroelectric PbTiO3.

    Science.gov (United States)

    Zhu, Jinlong; Zhang, Jianzhong; Xu, Hongwu; Vogel, Sven C; Jin, Changqing; Frantti, Johannes; Zhao, Yusheng

    2014-01-15

    Materials with zero/near zero thermal expansion coefficients are technologically important for applications in thermal management and engineering. To date, this class of materials can only be produced by chemical routes, either by changing chemical compositions or by composting materials with positive and negative thermal expansion. Here, we report for the first time a physical route to achieve near zero thermal expansion through application of pressure. In the stability field of tetragonal PbTiO3 we observed pressure-induced reversals between thermal contraction and expansion between ambient pressure and 0.9 GPa. This hybrid behavior leads to a mathematically infinite number of crossover points in the pressure-volume-temperature space and near-zero thermal expansion coefficients comparable to or even smaller than those attained by chemical routes. The observed pressures for this unusual phenomenon are within a small range of 0.1-0.9 GPa, potentially feasible for designing stress-engineered materials, such as thin films and nano-crystals, for thermal management applications.

  2. Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement.

    Science.gov (United States)

    Dinicola, Simona; Fabrizi, Gianmarco; Masiello, Maria Grazia; Proietti, Sara; Palombo, Alessandro; Minini, Mirko; Harrath, Abdel Halim; Alwasel, Saleh H; Ricci, Giulia; Catizone, Angela; Cucina, Alessandra; Bizzarri, Mariano

    2016-07-01

    Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A joined role of canopy and reversal cells in bone remodeling--lessons from glucocorticoid-induced osteoporosis.

    Science.gov (United States)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe; Bollerslev, Jens; Delaissé, Jean-Marie

    2015-04-01

    Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal- and glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e., uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces. In postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis of iliac crest biopsies from patients exposed to long-term glucocorticoid treatment revealed a subpopulation of reversal surfaces corresponding to the characteristics of arrest found in postmenopausal osteoporosis. Importantly, these arrested reversal surfaces were devoid of canopy coverage in almost all biopsies, and their prevalence correlated with a deficiency in bone forming surfaces. Taken together with the other recent data, the functional link between canopies, reversal surface activity, and the extent of bone formation surface in postmenopausal- and glucocorticoid-induced osteoporosis, supports a model where bone restitution during remodeling demands recruitment of osteoprogenitors from the canopy onto reversal surfaces. These data suggest that securing the presence of functional local osteoprogenitors deserves attention in the search of strategies to prevent the bone loss that occurs during bone remodeling in pathological situations. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

    Science.gov (United States)

    Warrington, Junie P; Csiszar, Anna; Mitschelen, Matthew; Lee, Yong Woo; Sonntag, William E

    2012-01-01

    Whole brain radiation therapy (WBRT) is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia) or 21% oxygen (normoxia) for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

  5. MRI study on reversible and irreversible electroporation induced blood brain barrier disruption.

    Directory of Open Access Journals (Sweden)

    Mohammad Hjouj

    Full Text Available Electroporation, is known to induce cell membrane permeabilization in the reversible (RE mode and cell death in the irreversible (IRE mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE, serial SPGR (DCE-MRI with flip angles ranging over 5-25°, and diffusion-weighted MRI (DWMRI. Blood brain barrier (BBB disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887±83 (arbitrary units immediately post treatment to 2246±94 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289±87. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.27±0.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50±10% of the T2W enhancing volumes on the day of the treatment which was 33±5% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions

  6. Frequent blood feeding enables insecticide-treated nets to reduce transmission by mosquitoes that bite predominately outdoors.

    Science.gov (United States)

    Russell, Tanya L; Beebe, Nigel W; Bugoro, Hugo; Apairamo, Allan; Chow, Weng K; Cooper, Robert D; Collins, Frank H; Lobo, Neil F; Burkot, Thomas R

    2016-03-10

    The effectiveness of vector control on malaria transmission by long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) depends on the vectors entering houses to blood feed and rest when people are inside houses. In the Solomon Islands, significant reductions in malaria have been achieved in the past 20 years with insecticide-treated bed nets, IRS, improved diagnosis and treatment with artemisinin combination therapies; despite the preference of the primary vector, Anopheles farauti, to feed outdoors and early in the evening and thereby avoid potential exposure to insecticides. Rational development of tools to complement LLINs and IRS by attacking vectors outdoor requires detailed knowledge of the biology and behaviours of the target species. Malaria transmission in Central Province, Solomon Islands was estimated by measuring the components comprising the entomological inoculation rate (EIR) as well as the vectorial capacity of An. farauti. In addition, the daily and seasonal biting behaviour of An. farauti, was examined and the duration of the feeding cycle was estimated with a mark-release-recapture experiment. Anopheles farauti was highly exophagic with 72% captured by human landing catches (HLC) outside of houses. Three-quarters (76%) of blood feeding on humans was estimated to occur before 21.00 h. When the hourly location of humans was considered, the proportion of exposure to mosquito bites on humans occurring indoors (πi) was only 0.130 ± 0.129. Peak densities of host seeking An. farauti occurred between October and January. The annual EIR was estimated to be 2.5 for 2012 and 33.2 for 2013. The length of the feeding cycle was 2.1 days. The short duration of the feeding cycle by this species offers an explanation for the substantial control of malaria that has been achieved in the Solomon Islands by LLINs and IRS. Anopheles farauti is primarily exophagic and early biting, with 13% of mosquitoes entering houses to feed late at night during

  7. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete

    2013-01-01

    is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central......, tesofensine produces weight loss together with reversal of lowered forebrain dopamine levels in DIO rats, suggesting that tesofensine's anti-obesity effects, at least in part, are associated with positive modulation of central dopaminergic activity....

  8. Reversible switching between pressure-induced amorphization and thermal-driven recrystallization in VO2(B) nanosheets.

    Science.gov (United States)

    Wang, Yonggang; Zhu, Jinlong; Yang, Wenge; Wen, Ting; Pravica, Michael; Liu, Zhenxian; Hou, Mingqiang; Fei, Yingwei; Kang, Lei; Lin, Zheshuai; Jin, Changqing; Zhao, Yusheng

    2016-07-18

    Pressure-induced amorphization (PIA) and thermal-driven recrystallization have been observed in many crystalline materials. However, controllable switching between PIA and a metastable phase has not been described yet, due to the challenge to establish feasible switching methods to control the pressure and temperature precisely. Here, we demonstrate a reversible switching between PIA and thermally-driven recrystallization of VO2(B) nanosheets. Comprehensive in situ experiments are performed to establish the precise conditions of the reversible phase transformations, which are normally hindered but occur with stimuli beyond the energy barrier. Spectral evidence and theoretical calculations reveal the pressure-structure relationship and the role of flexible VOx polyhedra in the structural switching process. Anomalous resistivity evolution and the participation of spin in the reversible phase transition are observed for the first time. Our findings have significant implications for the design of phase switching devices and the exploration of hidden amorphous materials.

  9. Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

    International Nuclear Information System (INIS)

    Stanford, N.; Dunne, D.P.

    2010-01-01

    Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

  10. Development of multifunctional metabolic synergists to suppress the evolution of resistance against pyrethroids in insects that blood feed on humans.

    Science.gov (United States)

    Hardstone, Melissa C; Strycharz, Joseph P; Kim, Junheon; Park, Il-Kwon; Yoon, Kyong Sup; Ahn, Young Joon; Harrington, Laura C; Lee, Si Hyeock; Clark, J Marshall

    2015-06-01

    Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public-health-related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (kdr), and prior extensive use of DDT has predisposed the pyrethroids to cross-resistance via kdr. Given the widespread occurrence of kdr, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects. 3-Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin-treated females of the ISOP450 strain of Culex pipiens quinquefasciatus resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, Cimex lectularius, and was 2.8-fold more synergistic than piperonyl butoxide (PBO). PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (Cx. p. quinquefasciatus) and in a public-health pest, C. lectularius, respectively, indicating a broad spectrum of action on blood-feeding insects. PBH appears to have residual properties similar to permethrin and is itself non-toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide-treated nets and home/residential sprays. © 2014 Society of Chemical Industry.

  11. Effects of a neem extract on blood feeding, oviposition and oocyte ultrastructure in Anopheles stephensi Liston (Diptera: Culicidae).

    Science.gov (United States)

    Lucantoni, L; Giusti, F; Cristofaro, M; Pasqualini, L; Esposito, F; Lupetti, P; Habluetzel, A

    2006-12-01

    Secondary metabolites of the neem tree (Azadirachta indica A. Juss., Meliaceae) exhibit a wide range of biological activities in insects. However, few studies have addressed the effects of neem extracts or compounds in arthropods of medical importance. In this study, a laboratory strain of Anopheles stephensi was used to assess the effects of a commercial formulation (Neem Azal) (NA)), containing azadirachtin A at 34%, on blood feeding, oviposition and oocyte ultrastructure. Oral administration of Neem Azal) to A. stephensi females through artificial blood meals did impair blood intake and oviposition in a concentration dependent manner. Similar results were obtained on females, which had consumed Neem Azal) in sucrose solution before taking a blood meal of plain blood. Neem treated females displayed a delay in oocyte development in both the phase of vitellogenesis and the phase of choriogenesis. The ultrastructural studies on ovaries from Neem Azal) treated females revealed distinct structural modifications indicative of: (i) a complete block of oogenesis, (ii) impairment of vitellogenesis and vitelline envelope formation, (iii) a severe degeneration of follicle cells. In agreement with results obtained in other insects, this study indicates that Neem Azal) impairs hormone control of oogenesis and exerts a cytotoxic effect on both follicular cells and oocytes of the Asian malaria vector A. stephensi.

  12. Neuropeptide signaling sequences identified by pyrosequencing of the American dog tick synganglion transcriptome during blood feeding and reproduction.

    Science.gov (United States)

    Donohue, Kevin V; Khalil, Sayed M S; Ross, E; Grozinger, Christina M; Sonenshine, Daniel E; Michael Roe, R

    2010-01-01

    Ticks are important vectors of numerous pathogens that impact human and animal health. The tick central nervous system represents an understudied area in tick biology and no tick synganglion-specific transcriptome has been described to date. Here we characterize whole or partial cDNA sequences of fourteen putative neuropeptides (allatostatin, insulin-like peptide, ion-transport peptide, sulfakinin, bursicon alpha/beta, eclosion hormone, glycoprotein hormone alpha/beta, corazonin, four orcokinins) and five neuropeptide receptors (gonadotropin receptor, leucokinin-like receptor, sulfakinin receptor, calcitonin receptor, pyrokinin receptor) translated from cDNA synthesized from the synganglion of unfed, partially fed and replete female American dog ticks, Dermacentor variabilis. Their homology to the same neuropeptides in other taxa is discussed. Many of these neuropeptides such as an allatostatin, insulin-like peptide, eclosion hormone, bursicon alpha and beta and glycoprotein hormone alpha and beta have not been previously described in the Chelicerata. An insulin-receptor substrate protein was also found indicating that an insulin signaling network is present in ticks. A putative type-2 proprotein processing convertase was also sequenced that may be involved in cleavage at monobasic and dibasic endoproteolytic cleavage sites in prohormones. The possible physiological role of the proteins discovered in adult tick blood feeding and reproduction will be discussed. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  13. Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pinch

    International Nuclear Information System (INIS)

    Lin, L.; Brower, D. L.; Ding, W. X.; Anderson, J. K.; Capecchi, W.; Eilerman, S.; Forest, C. B.; Koliner, J. J.; Nornberg, M. D.; Reusch, J.; Sarff, J. S.; Liu, D.

    2014-01-01

    Multiple bursty energetic-particle (EP) driven modes with fishbone-like structure are observed during 1 MW tangential neutral-beam injection in a reversed field pinch (RFP) device. The distinguishing features of the RFP, including large magnetic shear (tending to add stability) and weak toroidal magnetic field (leading to stronger drive), provide a complementary environment to tokamak and stellarator configurations for exploring basic understanding of EP instabilities. Detailed measurements of the EP mode characteristics and temporal-spatial dynamics reveal their influence on fast ion transport. Density fluctuations exhibit a dynamically evolving, inboard-outboard asymmetric spatial structure that peaks in the core where fast ions reside. The measured mode frequencies are close to the computed shear Alfvén frequency, a feature consistent with continuum modes destabilized by strong drive. The frequency pattern of the dominant mode depends on the fast-ion species. Multiple frequencies occur with deuterium fast ions compared to single frequency for hydrogen fast ions. Furthermore, as the safety factor (q) decreases, the toroidal mode number of the dominant EP mode transits from n=5 to n=6 while retaining the same poloidal mode number m=1. The transition occurs when the m=1, n=5 wave-particle resonance condition cannot be satisfied as the fast-ion safety factor (q fi ) decreases. The fast-ion temporal dynamics, measured by a neutral particle analyzer, resemble a classical predator-prey relaxation oscillation. It contains a slow-growth phase arising from the beam fueling followed by a rapid drop when the EP modes peak, indicating that the fluctuation-induced transport maintains a stiff fast-ion density profile. The inferred transport rate is strongly enhanced with the onset of multiple EP modes

  14. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

    DEFF Research Database (Denmark)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

    2014-01-01

    Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an ant....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant......-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated...

  15. Temperature induced reversible polymorphic phase transformations in a bis-hydrazone compound

    Science.gov (United States)

    Jayant, Vikrant; Das, Dinabandhu

    2018-03-01

    Two reversible polymorphic phase transformation of 2,3-butanedione, 2,3- bis[4,4‧-bis(diethylamino)benzophenone hydrazone] (DEBH) have been identified in DSC experiment. Topotactic phase transformation of three polymorphs has been observed in variable temperature Single Crystal X-ray Diffraction experiment. The reversible phase transformation of bulk material has been confirmed by Powder X-ray diffraction study.

  16. Electric-Field-Induced Magnetization Reversal in a Ferromagnet-Multiferroic Heterostructure

    Science.gov (United States)

    2011-11-14

    used to demonstrate an electrical control of the magnetic anisotropy via strain transfer to the ferromagnetic layer [4,5]. A magnetization reversal...22,23]; however, these studies were unable to achieve an 180 reversal of a magnetization. In this study, we probed the anisotropic magnetoresistance ...architecture was probed using PFM. The anisotropic strain imposed by DSO substrates [25] resulted in the formation of a simple, quasiperiodic

  17. Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial–Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α

    Directory of Open Access Journals (Sweden)

    Jiang Qian

    2018-01-01

    Full Text Available Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial–mesenchymal transition (EMT, driven by hypoxia-inducible factor 1α (HIF-1α, is involved in cancer progression and metastasis. The present study was designed to explore the role of propofol in hypoxia-induced resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine incorporation assay to measure cell viability and cell proliferation, respectively, in prostate cancer cell lines. Then, we detected HIF-1α, E-cadherin, and vimentin expression using western blotting. Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer cell lines. Propofol not only decreased hypoxia-induced HIF-1α expression, but also reversed hypoxia-induced EMT by suppressing HIF-1α. Furthermore, small interfering RNA–mediated silencing of HIF-1α reversed the hypoxia-induced docetaxel resistance, although there was little change in docetaxel sensitivity between the hypoxia group and propofol group. The induction of hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA knockdown conditions, the effects of propofol were obviated. These data support a role for propofol in regulating EMT in prostate cancer cells. Taken together, our findings demonstrate that propofol plays an important role in hypoxia-induced docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential drug for overcoming drug resistance in prostate cancer cells via HIF-1α suppression.

  18. Can mesenchymal stem cells reverse chronic stress-induced impairment of lung healing following traumatic injury?

    Science.gov (United States)

    Gore, Amy V; Bible, Letitia E; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

    2015-04-01

    One week following unilateral lung contusion (LC), rat lungs demonstrate full histologic recovery. When animals undergo LC plus the addition of chronic restraint stress (CS), wound healing is significantly delayed. Mesenchymal stem cells (MSCs) are pluripotent cells capable of immunomodulation, which have been the focus of much research in wound healing and tissue regeneration. We hypothesize that the addition of MSCs will improve wound healing in the setting of CS. Male Sprague-Dawley rats (n = 6-7 per group) were subjected to LC/CS with or without the injection of MSCs. MSCs were given as a single intravenous dose of 5 × 10 cells in 1 mL Iscove's Modified Dulbecco's Medium at the time of LC. Rats were subjected to 2 hours of restraint stress on Days 1 to 6 following LC. Seven days following injury, rats were sacrificed, and the lungs were examined for histologic evidence of wound healing using a well-established histologic lung injury score (LIS) to grade injury. LIS examines inflammatory cells/high-power field (HPF) averaged over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with scores ranging from 0 (normal) to 11 (highly damaged). Peripheral blood was analyzed by flow cytometry for the presence of T-regulatory (C4CD25FoxP3) cells. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). As previously shown, 7 days following isolated LC, LIS has returned to 0.83 (0.41), with a subscore of zero for inflammatory cells/HPF. The addition of CS results in an LIS of 4.4 (2.2), with a subscore of 1.9 (0.7) for inflammatory cells/HPF. Addition of MSC to LC/CS decreased LIS to 1.7 (0.8), with a subscore of zero for inflammatory cells/HPF. Furthermore, treatment of animals undergoing LC/CS with MSCs increased the %T-regulatory cells by 70% in animals undergoing LC/CS alone (12.9% [2.4]% vs. 6.2% [1.3%]). Stress-induced impairment of wound healing is reversed by the addition of MSCs given

  19. Tempol protects cardiomyocytes from nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity.

    Science.gov (United States)

    Liu, Yongmin; Shim, Eunwoo; Nguyen, Phuonggiang; Gibbons, Alexander T; Mitchell, James B; Poirier, Miriam C

    2014-05-01

    Nucleoside reverse transcriptase inhibitors (NRTIs), essential components of combinational therapies used for treatment of human immunodeficiency virus-1, damage heart mitochondria. Here, we have shown mitochondrial compromise in H9c2 rat cardiomyocytes exposed for 16 passages (P) to the NRTIs zidovudine (AZT, 50μM) and didanosine (ddI, 50μM), and we have demonstrated protection from mitochondrial compromise in cells treated with 200μM 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (Tempol) or 200μM 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethylpiperidine (Tempol-H), along with AZT/ddI, for 16P. Exposure to AZT/ddI caused a moderate growth inhibition at P3, P5, P7, and P13, which was not altered by addition of Tempol or Tempol-H. Mitochondrial oxidative phosphorylation capacity was determined as uncoupled oxygen consumption rate (OCR) by Seahorse XF24 Analyzer. At P5, P7, and P13, AZT/ddI-exposed cells showed an OCR reduction of 8.8-57.2% in AZT/ddI-exposed cells, compared with unexposed cells. Addition of Tempol or Tempol-H, along with AZT/ddI, resulted in OCR levels increased by about 300% above the values seen with AZT/ddI alone. The Seahorse data were further supported by electron microscopy (EM) studies in which P16 cells exposed to AZT/ddI/Tempol had less mitochondrial pathology than P16 cells exposed to AZT/ddI. Western blots of P5 cells showed that Tempol and Tempol-H upregulated expression of mitochondrial uncoupling protein-2 (UCP-2). However, Complex I activity that was reduced by AZT/ddI, was not restored in the presence of AZT/ddI/Tempol. Superoxide levels were increased in the presence of AZT/ddI and significantly decreased in cells exposed to AZT/3TC/Tempol at P3, P7, and P10. In conclusion, Tempol protects against NRTI-induced mitochondrial compromise, and UCP-2 plays a role through mild uncoupling.

  20. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

    Directory of Open Access Journals (Sweden)

    Junie P Warrington

    Full Text Available Whole brain radiation therapy (WBRT is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia or 21% oxygen (normoxia for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

  1. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae motivation and avidity to blood feed.

    Directory of Open Access Journals (Sweden)

    Rafael Maciel-de-Freitas

    Full Text Available BACKGROUND: Dengue virus (DENV is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. METHODOLOGY/PRINCIPAL FINDINGS: We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2 to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal and avidity (the likelihood to re-feed after an interrupted first blood-meal. To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding. Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. CONCLUSIONS/SIGNIFICANCE: DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed. As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  2. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae) motivation and avidity to blood feed.

    Science.gov (United States)

    Maciel-de-Freitas, Rafael; Sylvestre, Gabriel; Gandini, Mariana; Koella, Jacob C

    2013-01-01

    Dengue virus (DENV) is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2) to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal) and avidity (the likelihood to re-feed after an interrupted first blood-meal). To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding). Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative) mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed). As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  3. Brief exposure of embryos to steroids or aromatase inhibitor induces sex reversal in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Gennotte, Vincent; Mafwila Kinkela, Patrick; Ulysse, Bernard; Akian Djétouan, Dieudonné; Bere Sompagnimdi, Frédéric; Tomson, Thomas; Mélard, Charles; Rougeot, Carole

    2015-01-01

    This study aimed to develop sex reversal procedures targeting the embryonic period as tools to study the early steps of sex differentiation in Nile tilapia with XX, XY, and YY sexual genotypes. XX eggs were exposed to masculinizing treatments with androgens (17α-methyltestosterone, 11-ketotestosterone) or aromatase inhibitor (Fadrozole), whereas XY and YY eggs were subjected to feminizing treatments with estrogen analog (17α-ethynylestradiol). All treatments consisted of a single or double 4-hr immersion applied between 1 and 36 hour post-fertilization (hpf). Concentrations of active substances were 1000 or 2000 μg l(-1) in XX and XY, and 2000 or 6500 μg l(-1) in YY. Masculinizing treatments of XX embryos achieved a maximal sex reversal rate of 10% with an exposure at 24 hpf to 1000 μg l(-1) of 11-ketotestosterone or to 2000 μg l(-1) of Fadrozole. Feminization of XY embryos was more efficient and induced up to 91% sex reversal with an exposure to 2000 μg l(-1) of 17α-ethynylestradiol. Interestingly, similar treatments failed to reverse YY fish to females, suggesting either that a sex determinant linked to the Y chromosome prevents the female pathway when present in two copies, or that a gene present on the X chromosome is needed for the development of a female phenotype. © 2014 Wiley Periodicals, Inc.

  4. Efficacy of Blood Sources and Artificial Blood Feeding Methods in Rearing of Aedes aegypti (Diptera: Culicidae) for Sterile Insect Technique and Incompatible Insect Technique Approaches in Sri Lanka

    OpenAIRE

    Nayana Gunathilaka; Tharaka Ranathunge; Lahiru Udayanga; Wimaladharma Abeyewickreme

    2017-01-01

    Introduction Selection of the artificial membrane feeding technique and blood meal source has been recognized as key considerations in mass rearing of vectors. Methodology Artificial membrane feeding techniques, namely, glass plate, metal plate, and Hemotek membrane feeding method, and three blood sources (human, cattle, and chicken) were evaluated based on feeding rates, fecundity, and hatching rates of Aedes aegypti. Significance in the variations among blood feeding was investigated by one...

  5. Pathophysiology and long-term outcome of reversible tumor-like lesions induced by presenting status epilepticus.

    Science.gov (United States)

    Canas, Nuno; Soares, Pedro; Calado, Sofia; Pestana, Ricardo; Ribeiro, Constança; Vale, José

    2010-04-01

    Within the spectrum of reversible neuroimaging abnormalities induced by status epilepticus (SE) tumor-like lesions (TLL) have been rarely described. Their etiology, pathophysiology, and long-term outcome remain uncertain. These issues could be clarified by long-term magnetic resonance imaging (MRI) studies in TLL induced by presenting SE. Prospective multi-sequence MRI and clinical and electroencephalographic long-term (18 to 60 months) follow-up studies were performed in 3 patients with reversible TLL induced by presenting SE. In the peri-ictal MRI, TLL are hypointense in T1-weighted, hyperintense in T2-weighted, and fluid-attenuated inversion recovery images with a marked subcortical component and sulci effacement. The diffusion and MR-spectroscopy studies disclosed intermixed areas of increased/decreased diffusivity associated with a lactate peak and a decreased N-acetylaspartate. At long-term follow-up, none of the patients had seizure recurrence or electroencephalographic epileptiform abnormalities; MRI showed residual focal atrophy and gliosis associated with neuronal loss/dysfunction. SE per se may induce TLL. MRI multi-sequence studies disclosed that they are mainly formed by focal vasogenic and cytotoxic edema resulting from the hypermetabolism associated with seizure activity. In spite of a clinical favorable long-term outcome, the demonstration of irreversible brain damage argues in favor of immediate treatment of SE.

  6. Is the expression of autogeny by Culex molestus Forskal (Diptera: Culicidae) influenced by larval nutrition or by adult mating, sugar feeding, or blood feeding?

    Science.gov (United States)

    Kassim, Nur Faeza A; Webb, Cameron E; Russell, Richard C

    2012-06-01

    Culex molestus Forskal is suspected to have been introduced into southern Australia during the 1940s. Investigations to determine factors influencing the expression of autogeny, the response of this mosquito to potential blood meals, and the subsequent influence on oviposition were undertaken. Immature mosquitoes raised at five feeding regimes had mortality rates, development rates, wing length, and autogenous egg raft size measured. All surviving female mosquitoes laid autogenous eggs but there was a significant difference between the mean number of eggs per raft. For mosquitoes raised at each of the feeding regimes, there was a significant linear relationship between the number of eggs per autogenous egg raft and wing length. Newly emerged mosquitoes were offered a blood meal (i.e., rodent) daily but no blood feeding occurred until the autogenous egg raft was laid. There was no statistical difference in the rate of autogenous oviposition or post-oviposition blood feeding between control or treatment groups. The results of this study indicate that Cx. molestus is perfectly adapted to subterranean habitats in close association with human habitation, but their preference to delay blood feeding until up to day 8 following emergence may reduce their relative importance as a vector of arboviruses. © 2012 The Society for Vector Ecology.

  7. Influence of domain structure induced coupling on magnetization reversal of Co/Pt/Co film with perpendicular anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Matczak, Michał [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Schäfer, Rudolf [Leibniz Institute for Solid State and Materials Research (IFW) Dresden, Institute for Metallic Materials, PO 270116, D-01171 Dresden (Germany); Dresden University of Technology, Institute for Materials Science, D-01062 Dresden (Germany); Urbaniak, Maciej; Kuświk, Piotr; Szymański, Bogdan; Schmidt, Marek; Aleksiejew, Jacek [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); Stobiecki, Feliks, E-mail: Feliks.Stobiecki@ifmpan.poznan.pl [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

    2017-01-15

    A magnetic multilayer of substrate/Pt-15 nm/Co-0.8 nm/Pt-wedge 0–7 nm/Co-0.6 nm/Pt-2 nm structure is characterized by a perpendicular anisotropy of the Co layers and by graded interlayer coupling between them. Using magnetooptical Kerr microscopy we observed a distinct influence of magnetic domains in one Co layer on the nucleation field and positions of nucleation sites of reversed domains in the second Co layer. For sufficiently strong interlayer coupling a replication of magnetic domains from the magnetically harder layer to the magnetically softer layer is observed. - Highlights: • Co/Pt-wedge/Co layered film is characterized by a gradient of interlayer coupling. • Magnetic field controls propagation of straight domain wall. • Replication of magnetic domains in multilayers with strong ferromagnetic coupling. • Coupling induced by domains influences magnetization reversal of spin valves.

  8. On the relation between quasi-static and dynamic stress induced reversible structural relaxation of amorphous alloys

    International Nuclear Information System (INIS)

    Krueger, P.; Stucky, T.; Boewe, M.; Neuhaeuser, H.

    1993-01-01

    Quasi-static stress relaxation and dynamic internal friction measurements of stress induced reversible structural relaxation were performed on the amorphous alloy Fe 40 Ni 40 B 20 . The kinetics can be well described by a stretched exponential Kohlrausch-Williams-Watts quasi-static relaxation. The thermally activated part of the internal friction shows an Arrhenius temperature behaviour for a fixed vibration frequency and an inverse power frequency behaviour for a fixed temperature. The activation energies calculated from the Arrhenius equation and from the frequency shift method are significantly different. In order to explain this discrepancy the relation between the quasi-static and the dynamic descriptions of the reversible relaxation is reexamined. In particular it is shown that these two activation energies are connected by the Kohlrausch exponent of the quasi-static relaxation. (orig.)

  9. Nanostructured graphite-induced destabilization of LiBH4 for reversible hydrogen storage

    CSIR Research Space (South Africa)

    Wang, K

    2016-11-01

    Full Text Available In this study, nanostructured graphite (nano-G) was added to LiBH(sub4) and examined with respect to its effect on the hydrogen storage properties of the system. Our study found that nano-G is an effective additive for promoting the reversible...

  10. Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

    DEFF Research Database (Denmark)

    Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

    2009-01-01

    and the transepithelial stimulation of leukocytes were nearly completely abolished after the apical supplementation of PC with CPBS, but not by CPBS alone. Ethanol up to 66 mM was not able to reverse this effect. CONCLUSIONS: A considerable part of the therapeutic and preventive effect of PC supplementation in ALD might...

  11. Crack Cocaine-Induced Cardiac Conduction Abnormalities Are Reversed by Sodium Bicarbonate Infusion

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Miranda

    2013-01-01

    Full Text Available We report a dramatic case of a 19-year-old man with crack cocaine overdose with important clinical complications as cardiac arrest due to ventricular fibrillation and epileptics status. During this intoxication, electrocardiographic abnormalities similar to those found in tricyclic antidepressant poisoning were observed, and they were reversed by intravenous sodium bicarbonate infusion.

  12. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium....

  13. Efficacy of larvicidal activity of green synthesized titanium dioxide nanoparticles using Mangifera indica extract against blood-feeding parasites.

    Science.gov (United States)

    Rajakumar, Govindasamy; Rahuman, Abdul Abdul; Roopan, Selvaraj Mohana; Chung, Ill-Min; Anbarasan, Karunanithi; Karthikeyan, Viswanathan

    2015-02-01

    , simple, and eco-friendly approach has been suggested to control blood-feeding parasites.

  14. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents.

    Science.gov (United States)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte; Gould, Robert W; Grannan, Michael; Noetzel, Meredith J; Lamsal, Atin; Niswender, Colleen M; Daniels, J Scott; Poslusney, Michael S; Melancon, Bruce J; Tarr, James C; Byers, Frank W; Wess, Jürgen; Duggan, Mark E; Dunlop, John; Wood, Michael W; Brandon, Nicholas J; Wood, Michael R; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

    2014-10-15

    Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders.

  15. Current-induced alternating reversed dual-echo-steady-state for joint estimation of tissue relaxation and electrical properties.

    Science.gov (United States)

    Lee, Hyunyeol; Sohn, Chul-Ho; Park, Jaeseok

    2017-07-01

    To develop a current-induced, alternating reversed dual-echo-steady-state-based magnetic resonance electrical impedance tomography for joint estimation of tissue relaxation and electrical properties. The proposed method reverses the readout gradient configuration of conventional, in which steady-state-free-precession (SSFP)-ECHO is produced earlier than SSFP-free-induction-decay (FID) while alternating current pulses are applied in between the two SSFPs to secure high sensitivity of SSFP-FID to injection current. Additionally, alternating reversed dual-echo-steady-state signals are modulated by employing variable flip angles over two orthogonal injections of current pulses. Ratiometric signal models are analytically constructed, from which T 1 , T 2 , and current-induced B z are jointly estimated by solving a nonlinear inverse problem for conductivity reconstruction. Numerical simulations and experimental studies are performed to investigate the feasibility of the proposed method in estimating relaxation parameters and conductivity. The proposed method, if compared with conventional magnetic resonance electrical impedance tomography, enables rapid data acquisition and simultaneous estimation of T 1 , T 2 , and current-induced B z , yielding a comparable level of signal-to-noise ratio in the parameter estimates while retaining a relative conductivity contrast. We successfully demonstrated the feasibility of the proposed method in jointly estimating tissue relaxation parameters as well as conductivity distributions. It can be a promising, rapid imaging strategy for quantitative conductivity estimation. Magn Reson Med 78:107-120, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  16. Effects of strain-induced martensite and its reversion on the magnetic properties of AISI 201 austenitic stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Souza Filho, I.R. [Escola de Engenharia de Lorena, University of Sao Paulo, 12602-810 Lorena (Brazil); Sandim, M.J.R., E-mail: msandim@demar.eel.usp.br [Escola de Engenharia de Lorena, University of Sao Paulo, 12602-810 Lorena (Brazil); Cohen, R.; Nagamine, L.C.C.M. [Instituto de Física, University of Sao Paulo, 05314-970 Sao Paulo (Brazil); Hoffmann, J. [Karlsruher Institut für Technologie, D-72061 Karlsruhe (Germany); Bolmaro, R.E. [Instituto de Física Rosario, CONICET-UNR, 2000 Rosario (Argentina); Sandim, H.R.Z. [Escola de Engenharia de Lorena, University of Sao Paulo, 12602-810 Lorena (Brazil)

    2016-12-01

    Strain-induced martensite (SIM) and its reversion in a cold-rolled AISI 201 austenitic stainless steel was studied by means of magnetic properties, light optical (LOM) and scanning electron (SEM) microscopy, electron backscatter diffraction (EBSD), texture measurements, and Vickers microhardness testing. According to Thermo-calc© predictions, the BCC phase (residual δ-ferrite and SIM) is expected to be stable until 600 °C. The current material was cold rolled up to 60% thickness reduction and submitted to both isothermal and stepwise annealing up to 800 °C. Magnetic measurements were taken during annealing (in situ) of the samples and also for their post mortem conditions. The Curie temperatures (T{sub c}) of residual δ-ferrite and SIM have similar values between 550 and 600 °C. Besides T{sub c}, the focused magnetic parameters were saturation magnetization (M{sub s}), remanent magnetization (M{sub R}), and coercive field (H{sub c}). SIM reversion was found to occur in the range of 600–700 °C in good agreement with Thermo-calc© predictions. The microstructures of the material, annealed at 600 and 700 °C for 1 h, were investigated via EBSD. Microtexture measurements for these samples revealed that the texture components were mainly those found for the 60% cold rolled material. This is an evidence that the SIM reversion occurred by an athermal mechanism. - Highlights: • H{sub c} and M{sub R}/M{sub S} ratio give information about distribution of strain-induced martensite. • According to Thermo-calc©, the BCC phase in AISI 201 steel is stable until 600 °C. • Thermo-calc predictions agrees with magnetic properties of AISI 201 steel. • Possible magnetic anisotropy induced by rolling in AISI 201 steel is investigated.

  17. Radiation-induced magnetization reversal causing a large flux loss in undulator permanent magnets.

    Science.gov (United States)

    Bizen, Teruhiko; Kinjo, Ryota; Hasegawa, Teruaki; Kagamihata, Akihiro; Kida, Yuichiro; Seike, Takamitsu; Watanabe, Takahiro; Hara, Toru; Itoga, Toshiro; Asano, Yoshihiro; Tanaka, Takashi

    2016-11-29

    We report an unexpectedly large flux loss observed in permanent magnets in one of the undulators operated in SACLA, the x-ray free electron laser facility in Japan. Characterizations of individual magnets extracted from the relevant undulator have revealed that the flux loss was caused by a homogeneous magnetization reversal extending over a wide area, but not by demagnetization of individual magnets damaged by radiation. We show that the estimated flux-loss rate is much higher than what is reported in previous papers, and its distribution is much more localized to the upstream side. Results of numerical and experimental studies carried out to validate the magnetization reversal and quantify the flux loss are presented, together with possible countermeasures against rapid degradation of the undulator performance.

  18. Selective Solvent Induced Reversible Surface Reconstruction of Diblock Copolymer Thin Films

    Energy Technology Data Exchange (ETDEWEB)

    Xu, T.; Misner, M.J.; Kim, S.; Sievert, J.D.; Gang, O.; Ocko, B.; Russell, T.P. (UMASS, Amherst); (BNL)

    2006-03-08

    Through the use of a selective solvent a reversible surface reconstruction of diblock copolymer thin films was observed. The solvent selectivity and solubility of the minor component block were found to be crucial to generate nanoporous films with pores that penetrate through entire film thickness. The process was shown to be reversible by thermal annealing and was easily monitored using in-situ grazing incidence small angle x-ray scattering and scanning force microscopy. At temperatures of 60-90 C, only a small fraction of the nanopores relaxed to regenerate the original nanotemplate. However, by heating to 90-100 C, the original nanotemplate was completely regenerated. Even though the bulk mobility of PS and PMMA is low at these temperatures, the local mobility required to regenerate the template was sufficient.

  19. Redox-induced reversible luminescence switching of cerium-doped upconversion nanoparticles

    International Nuclear Information System (INIS)

    Huang, Yanan; Xiao, Qingbo; Wang, Jian; Xi, Yonglan; Li, Fujin; Feng, Yamin; Shi, Liyi; Lin, Hongzhen

    2016-01-01

    Smart upconversion nanophosphors (UCNPs) that can be reversibly switched between two or more luminescent states by certain external stimuli have attracted considerable attention due to their great potential in biological applications. Here we report for the first time a type of redox-switchable UCNPs by codoping NaGdF 4 :Yb/Er nanorods with the redox-active Ce 3+ /Ce 4+ ion pairs. A reversible switching of their UC luminescence intensity was observed upon the variation of the surrounding redox environments. We show solid proof that the luminescence switching is caused by the tailoring of the NaGdF 4 host crystal structure in response to changing redox state of the codoped cerium ions. A proof-of-concept example is further demonstrated by using these UCNPs for probing the dynamical variation of redox environments in biological tissues. - Highlights: • Synthesis of upconversion nanoparticles doped with Ce 3+ /Ce 4+ ions. • The precise and reversible modification of crystal structure by redox reactions. • Tuning the upconversion luminescence by tailoring the crystal structure.

  20. Effects of strain-induced martensite and its reversion on the magnetic properties of AISI 201 austenitic stainless steel

    Science.gov (United States)

    Souza Filho, I. R.; Sandim, M. J. R.; Cohen, R.; Nagamine, L. C. C. M.; Hoffmann, J.; Bolmaro, R. E.; Sandim, H. R. Z.

    2016-12-01

    Strain-induced martensite (SIM) and its reversion in a cold-rolled AISI 201 austenitic stainless steel was studied by means of magnetic properties, light optical (LOM) and scanning electron (SEM) microscopy, electron backscatter diffraction (EBSD), texture measurements, and Vickers microhardness testing. According to Thermo-calc© predictions, the BCC phase (residual δ-ferrite and SIM) is expected to be stable until 600 °C. The current material was cold rolled up to 60% thickness reduction and submitted to both isothermal and stepwise annealing up to 800 °C. Magnetic measurements were taken during annealing (in situ) of the samples and also for their post mortem conditions. The Curie temperatures (Tc) of residual δ-ferrite and SIM have similar values between 550 and 600 °C. Besides Tc, the focused magnetic parameters were saturation magnetization (Ms), remanent magnetization (MR), and coercive field (Hc). SIM reversion was found to occur in the range of 600-700 °C in good agreement with Thermo-calc© predictions. The microstructures of the material, annealed at 600 and 700 °C for 1 h, were investigated via EBSD. Microtexture measurements for these samples revealed that the texture components were mainly those found for the 60% cold rolled material. This is an evidence that the SIM reversion occurred by an athermal mechanism.

  1. Superhydrophobic TiO2-polymer nanocomposite surface with UV-induced reversible wettability and self-cleaning properties.

    Science.gov (United States)

    Xu, Qian Feng; Liu, Yang; Lin, Fang-Ju; Mondal, Bikash; Lyons, Alan M

    2013-09-25

    Multifunctional superhydrophobic nanocomposite surfaces based on photocatalytic materials, such as fluorosilane modified TiO2, have generated significant research interest. However, there are two challenges to forming such multifunctional surfaces with stable superhydrophobic properties: the photocatalytic oxidation of the hydrophobic functional groups, which leads to the permanent loss of superhydrophobicity, as well as the photoinduced reversible hydrolysis of the catalytic particle surface. Herein, we report a simple and inexpensive template lamination method to fabricate multifunctional TiO2-high-density polyethylene (HDPE) nanocomposite surfaces exhibiting superhydrophobicity, UV-induced reversible wettability, and self-cleaning properties. The laminated surface possesses a hierarchical roughness spanning the micro- to nanoscale range. This was achieved by using a wire mesh template to emboss the HDPE surface creating an array of polymeric posts while partially embedding untreated TiO2 nanoparticles selectively into the top surface of these features. The surface exhibits excellent superhydrophobic properties immediately after lamination without any chemical surface modification to the TiO2 nanoparticles. Exposure to UV light causes the surface to become hydrophilic. This change in wettability can be reversed by heating the surface to restore superhydrophobicity. The effect of TiO2 nanoparticle surface coverage and chemical composition on the mechanism and magnitude of wettability changes was studied by EDX and XPS. In addition, the ability of the surface to shed impacting water droplets as well as the ability of such droplets to clean away particulate contaminants was demonstrated.

  2. Stress-induced visceral hypersensitivity in maternally separated rats can be reversed by peripherally restricted histamine-1-receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Oana I Stanisor

    Full Text Available BACKGROUND: The histamine-1 receptor (H1R antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats. METHODS: The visceromotor response to colonic distension was assessed in adult maternally separated and nonhandled rats pre- and 24 hours post water avoidance. Subsequently rats were treated with vehicle alone or different dosages of fexofenadine (1.8 and 18 mg/kg or ebastine (0.1 and 1.0 mg/kg and re-evaluated. Colonic tissue was collected to assess relative RMCP-2 and occludin expression levels by Western blot and histamine-1 receptor by RT-qPCR. β-hexosaminidase release by RBL-2H3 cells was used to establish possible mast cell stabilizing properties of the antagonists. KEY RESULTS: Water avoidance only induced enhanced response to distension in maternally separated rats. This response was reversed by 1.8 and 18 mg/kg fexofenadine. Reversal was also obtained by 1.0 but not 0.1 mg/kg ebastine. RMCP-2 expression levels were comparable in these two ebastine treatment groups but occludin was significantly higher in 1.0 mg/kg treated rats. There were no differences in histamine-1 receptor expression between nonhandled and maternally separated rats. Fexofenadine but not ebastine showed mast cell stabilizing quality. CONCLUSIONS: Our results indicate that the peripherally restricted 2(nd generation H1-receptor antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rat. These data justify future IBS patient trials with these well tolerated compounds.

  3. Low-pH induced reversible reorganizations of chloroplast thylakoid membranes - As revealed by small-angle neutron scattering.

    Science.gov (United States)

    Ünnep, Renáta; Zsiros, Ottó; Hörcsik, Zsolt; Markó, Márton; Jajoo, Anjana; Kohlbrecher, Joachim; Garab, Győző; Nagy, Gergely

    2017-05-01

    Energization of thylakoid membranes brings about the acidification of the lumenal aqueous phase, which activates important regulatory mechanisms. Earlier Jajoo and coworkers (2014 FEBS Lett. 588:970) have shown that low pH in isolated plant thylakoid membranes induces changes in the excitation energy distribution between the two photosystems. In order to elucidate the structural background of these changes, we used small-angle neutron scattering on thylakoid membranes exposed to low p 2 H (pD) and show that gradually lowering the p 2 H from 8.0 to 5.0 causes small but well discernible reversible diminishment of the periodic order and the lamellar repeat distance and an increased mosaicity - similar to the effects elicited by light-induced acidification of the lumen. Our data strongly suggest that thylakoids dynamically respond to the membrane energization and actively participate in different regulatory mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Reversal of Cadmium-induced Oxidative Stress in Chicken by Herbal Adaptogens Withania Somnifera and Ocimum Sanctum.

    Science.gov (United States)

    Bharavi, K; Reddy, A Gopala; Rao, G S; Reddy, A Rajasekhara; Rao, S V Rama

    2010-07-01

    The present study was carried out to evaluate the herbal adaptogens Withania somnifera and Ocimum sanctum on cadmium-induced oxidative toxicity in broiler chicken. Cadmium administration at the rate of 100 ppm orally along with feed up to 28 days produced peroxidative damage, as indicated by increase in TBARS, reduction in glutathione (GSH) concentration in liver and kidney, and increase in catalase (CAT) and superoxide dismutase (SOD) of erythrocytes. Herbal adaptogens Withania somnifera roots and Ocimum sanctum leaf powder administration at the rate of 0.1% through feed reversed the antioxidant enzyme of RBC, i.e., CAT and SOD, nonenzymatic antioxidants GSH and lipid peroxidation marker TBARS of liver and kidney. Liver and kidney tissue repair and normal function was assessed by alanine aminotransaminase for liver and creatinine and blood urea nitrogen for kidney. In conclusion, oral administration of Withania somnifera root and Ocimum sanctum leaf powder prevented cadmium-induced peroxidation of tissues.

  5. RECOMBINANT HUMAN INTERLEUKIN-6 INDUCES A RAPID AND REVERSIBLE ANEMIA IN CANCER-PATIENTS

    NARCIS (Netherlands)

    NIEKEN, J; MULDER, NH; VELLENGA, E; LIMBURG, PC; PIERS, DA; DEVRIES, EGE

    1995-01-01

    Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II

  6. βCCT, AN ANTAGONIST SELECTIVE FOR α1 GABAA RECEPTORS, REVERSES DIAZEPAM WITHDRAWAL-INDUCED ANXIETY IN RATS

    Science.gov (United States)

    Divljaković, Jovana; Milić, Marija; Namjoshi, Ojas A.; Tiruveedhula, Veera V.; Timić, Tamara; Cook, James M.; Savić, Miroslav M.

    2012-01-01

    The abrupt discontinuation of prolonged benzodiazepine treatment elicits a withdrawal syndrome with increased anxiety as a major symptom. The neural mechanisms underlying benzodiazepine physical dependence are still insufficiently understood. Flumazenil, the non-selective antagonist of the benzodiazepine binding site of GABAA receptors was capable of preventing and reversing the increased anxiety during benzodiazepine withdrawal in animals and humans in some, but not all studies. On the other hand, a number of data suggest that GABAA receptors containing α1 subunits are critically involved in processes developing during prolonged use of benzodiazepines, such are tolerance to sedative effects, liability to physical dependence and addiction. Hence, we investigated in the elevated plus maze the level of anxiety 24 h following 21 days of diazepam treatment and the influence of flumazenil or a preferential α1-subunit selective antagonist βCCt on diazepam withdrawal syndrome in rats. Abrupt cessation of protracted once-daily intraperitoneal administration of 2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety-like behavior in the elevated plus maze 24 h after treatment cessation. Acute challenge with either flumazenil (10 mg/kg) or βCCt (1.25, 5 and 20 mg/kg) alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists induced an anxiolytic-like response close, though not identical, to that seen with acute administration of diazepam. These findings imply that the mechanism by which antagonism at GABAA receptors may reverse the withdrawal-induced anxiety involves the α1 subunit and prompt further studies aimed at linking the changes in behavior with possible adaptive changes in subunit expression and function of GABAA receptors. PMID:23149168

  7. Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea.

    Science.gov (United States)

    Castro-Grattoni, Anabel L; Alvarez-Buvé, Roger; Torres, Marta; Farré, Ramon; Montserrat, Josep M; Dalmases, Mireia; Almendros, Isaac; Barbé, Ferran; Sánchez-de-la-Torre, Manuel

    2016-06-01

    Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment. We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia. Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment. The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  8. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis.

    Science.gov (United States)

    Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B; da Motta, Leonardo L; Klamt, Fabio; Ibañez, Irene L; Durán, Hebe

    2016-07-05

    Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.

  9. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

    Science.gov (United States)

    Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B.; da Motta, Leonardo L.; Klamt, Fabio; Ibañez, Irene L.; Durán, Hebe

    2016-01-01

    Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy. PMID:27206672

  10. Correlated electric-field induced reversal of antiferromagnetic order and surface magnetization in magnetoelectric Cr2O3

    Science.gov (United States)

    Wang, Junlei; Singh, Uday; Binek, Christian

    The electric-field-induced Faraday effect in magnetoelectrics comprises a superimposition of linear electric field responses with temperature dependencies of the linear magnetoelectric susceptibility and the antiferromagnetic order parameter. The tunability of the relative strength between the two contributions leads to a table-top set-up allowing to measure voltage-controlled selection and temperature dependence of the antiferromagnetic order parameter. Simultaneous measurement of the polar Kerr effect and the electric-field-induced Faraday effect is utilized to investigate correlated formation and switching of the surface magnetization and bulk antiferromagnetic order in Cr2O3 The correlated reversal of surface or boundary magnetization in response to voltage-controlled reversal of the bulk antiferromagnetic order parameter is of key importance for applications in spintronic devices such as the magnetoelectric MRAM. The Faraday rotation per applied voltage is independent of the sample thickness making the method scalable and versatile for thin film investigations. Scalability, compactness, and simplicity of the data analysis combined with low photon flux requirements make the Faraday approach advantageous for the investigation of the otherwise difficult to access voltage-controlled switching of antiferromagnetic domain states in magnetoelectric thin films. Acknowledgment: This project was supported by SRC through CNFD, an SRC-NRI Center, by C-SPIN, part of STARnet, and by the NSF through MRSEC DMR-0820521.

  11. Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.

    Science.gov (United States)

    O'Leary, Valerie B; Marchetti, Christine M; Krishnan, Raj K; Stetzer, Bradley P; Gonzalez, Frank; Kirwan, John P

    2006-05-01

    Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

  12. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    DEFF Research Database (Denmark)

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

    2009-01-01

    activation of human leukocytes. For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 m...... of leukocytes were nearly completely abolished after the apical supplementation of PC with CPBS, but not by CPBS alone. Ethanol up to 66 mM was not able to reverse this effect. A considerable part of the therapeutic and preventive effect of PC supplementation in ALD might result from a reduction of ethanol...

  13. Epicutaneous immunization with protein antigen TNP-Ig and NOD2 ligand muramyl dipeptide (MDP) reverses skin-induced suppression of contact hypersensitivity.

    Science.gov (United States)

    Majewska-Szczepanik, Monika; Dorożyńska, Iwona; Strzępa, Anna; Szczepanik, Marian

    2014-02-01

    Epicutaneous (EC) immunization offers a new method of a needle-free and self-administrable immunization by using a topically applied patch to deliver vaccine. We have previously shown that EC immunization with hapten-conjugated protein antigen TNP-Ig prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. Our further work showed that EC immunization with TNP-Ig and Toll-like receptor (TLR) ligands prior to hapten sensitization reverses skin-induced suppression. Animal model of contact hypersensitivity was used to study reversal of skin-induced suppression. Current work showed that EC immunization with protein antigen TNP-Ig and MDP NOD2 agonist - muramyldipeptide (L isoform) reverses skin-induced suppression of CHS. On the other hand L18-MDP NOD2 agonist - muramyldipeptide with a C18 fatty acid chain and MDP control - negative control for MDP - muramyldipeptide (D isoform, inactive) did not reverse skin-induced suppression. "Transfer in" experiment showed that reversal of skin-induced suppression can be adoptively transferred with lymphoid cells isolated from donors EC treated with TNP-Ig and MDP NOD2 agonist. Moreover, experiment employing two non-cross-reacting antigens TNP-Ig and OX-Ig proved that reversal of skin-induced suppression is antigen specific. Additionally, lymph node cells isolated from mice EC immunized with TNP-Ig and MDP NOD2 agonist produced increased level of IFN-γ suggesting that this cytokine might be involved in reversal of skin-induced suppression. This work shows that EC immunization with protein antigen plus NOD2 ligand MDP may be a potential tool to increase the immunogenicity of weekly immunogenic antigens. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Reversal of chemotherapy-induced leukopenia using granulocyte macrophage colony-stimulating factor promotes bone metastasis that can be blocked with osteoclast inhibitors.

    Science.gov (United States)

    Dai, Jinlu; Lu, Yi; Yu, Chunyan; Keller, Jill M; Mizokami, Atsushi; Zhang, Jian; Keller, Evan T

    2010-06-15

    Hematopoietic growth factors are used to reverse chemotherapy-induced leukopenia. However, some factors such as granulocyte macrophage colony-stimulating factor (GM-CSF) induce osteoclast-mediated bone resorption that can promote cancer growth in the bone. Accordingly, we evaluated the ability of GM-CSF to promote bone metastases of breast cancer or prostate cancer in a mouse model of chemotherapy-induced leukopenia. In this model, GM-CSF reversed cyclophosphamide-induced leukopenia but also promoted breast cancer and prostate cancer growth in the bone but not in soft tissue sites. Bone growth was associated with the induction of osteoclastogenesis, yet in the absence of tumor GM-CSF, it did not affect osteoclastogenesis. Two osteoclast inhibitors, the bisphosphonate zoledronic acid and the RANKL inhibitor osteoprotegerin, each blocked GM-CSF-induced tumor growth in the bone but did not reverse the ability of GM-CSF to reverse chemotherapy-induced leukopenia. Our findings indicate that it is possible to dissociate the bone-resorptive effects of GM-CSF, to reduce metastatic risk, from the benefits of this growth factor in reversing leukopenia caused by treatment with chemotherapy.

  15. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    International Nuclear Information System (INIS)

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-01-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

  16. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    Energy Technology Data Exchange (ETDEWEB)

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-12-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and /sup 45/Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in /sup 45/Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker.

  17. Steam-cooking rapidly destroys and reverses onion-induced antiplatelet activity

    Directory of Open Access Journals (Sweden)

    Hansen Emilie A

    2012-09-01

    Full Text Available Abstract Background Foods in the diet that can aid in the prevention of diseases are of major interest. Onions are key ingredients in many cuisines around the world and moreover, onion demand has trended higher over the past three decades. An important pharmacological aspect of onion is the ability to inhibit platelet aggregation. Raw onions inhibit platelet aggregation; however, when onions are boiled or heated, antiplatelet activity may be abolished. Methods Onion quarters were steamed for 0, 1, 3, 6, 10, and 15 min. The in vitro antiplatelet activity of a yellow hybrid storage onion was examined at these times on the blood of 12 human subjects using in vitro whole blood aggregometry. Results Contrary to findings reported for boiling, antiplatelet activity was destroyed between 3 and 6 min of steaming, and at 10 min of steaming, cooked onions stimulated platelet activity. Extracts from cooked onion had the potential to reverse the inhibitory effect on blood platelets by 25%. Responses were consistent across all donors. Total polyphenolic concentration and soluble solids were not affected by steaming time. Conclusions The potential value of cooked onion preparations may result in destruction or reversal of antiplatelet activity, without affecting the polyphenolic concentration.

  18. Steam-cooking rapidly destroys and reverses onion-induced antiplatelet activity.

    Science.gov (United States)

    Hansen, Emilie A; Folts, John D; Goldman, Irwin L

    2012-09-20

    Foods in the diet that can aid in the prevention of diseases are of major interest. Onions are key ingredients in many cuisines around the world and moreover, onion demand has trended higher over the past three decades. An important pharmacological aspect of onion is the ability to inhibit platelet aggregation. Raw onions inhibit platelet aggregation; however, when onions are boiled or heated, antiplatelet activity may be abolished. Onion quarters were steamed for 0, 1, 3, 6, 10, and 15 min. The in vitro antiplatelet activity of a yellow hybrid storage onion was examined at these times on the blood of 12 human subjects using in vitro whole blood aggregometry. Contrary to findings reported for boiling, antiplatelet activity was destroyed between 3 and 6 min of steaming, and at 10 min of steaming, cooked onions stimulated platelet activity. Extracts from cooked onion had the potential to reverse the inhibitory effect on blood platelets by 25%. Responses were consistent across all donors. Total polyphenolic concentration and soluble solids were not affected by steaming time. The potential value of cooked onion preparations may result in destruction or reversal of antiplatelet activity, without affecting the polyphenolic concentration.

  19. Effects of insemination and blood-feeding on locomotor activity of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) females under laboratory conditions.

    Science.gov (United States)

    Lima-Camara, Tamara Nunes; Lima, José Bento Pereira; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio

    2014-07-02

    Dengue is an arbovirus disease transmitted by two Aedes mosquitoes: Ae. aegypti and Ae. albopictus. Virgin females of these two species generally show a bimodal and diurnal pattern of activity, with early morning and late afternoon peaks. Although some studies on the flight activity of virgin, inseminated and blood-fed Ae. aegypti females have been carried out under laboratory conditions, little is known about the effects of such physiological states on the locomotor activity of Ae. albopictus and Ae. aegypti females. The aim of this study was to analyze, under laboratory conditions, the effects of insemination and blood-feeding on the locomotor activity of Ae. albopictus and Ae. aegypti females under LD 12:12, at 25°C. Both Ae. albopictus and Ae. aegypti females were obtained from established laboratory colonies. Control groups were represented by virgin/unfed Ae. albopictus and Ae. aegypti females. Experiments were conducted under laboratory conditions, using an activity monitor that registers individual activity every thirty minutes. Virgin/unfed Ae. albopictus and Ae. aegypti females showed a diurnal and bimodal pattern of locomotor activity, with peaks at early morning and late afternoon. Insemination and blood-feeding significantly decreased the locomotor activity of Ae. aegypti females, but inseminated/blood-fed Ae. aegypti and Ae. albopictus females showed a similar significant decrease on the locomotor activity compared to virgin/unfed females. This study is the first demonstration of the effects of insemination and blood-feeding on the locomotor activity of Ae. albopictus and Ae. aegypti females under artificial conditions. Data suggest that Ae. albopictus and Ae. aegypti females respond in different ways to physiological status changes and such divergence between these two dengue vectors, associated with several ecological differences, could be related to the greater dengue vectorial capacity of Ae. aegypti in Americas in comparison to Ae. albopictus.

  20. Blood Feeding Status, Gonotrophic Cycle and Survivorship of Aedes (Stegomyia) aegypti (L.) (Diptera: Culicidae) Caught in Churches from Merida, Yucatan, Mexico.

    Science.gov (United States)

    Baak-Baak, C M; Ulloa-Garcia, A; Cigarroa-Toledo, N; Tzuc Dzul, J C; Machain-Williams, C; Torres-Chable, O M; Navarro, J C; Garcia-Rejon, J E

    2017-12-01

    Blood-feeding status, gonotrophic cycle, and survival rates of Aedes (Stegmyia) aegypti (L.) was investigated in catholic churches from Merida, Yucatan. Female Ae. aegypti were caught using backpack aspirator during 25 consecutive days in rainy (2015) and dry season (2016). Blood-feeding status was determined by external examination of the abdomen and classified as unfed, fed, and gravid. Daily changes in the parous-nulliparous ratio were recorded, and the gonotrophic cycle length was estimated by a time series analysis. Also, was observed the vitellogenesis to monitoring egg maturity. In total, 408 females Ae. aegypti were caught, and there was a significant difference in the number of females collected per season (Z = -6.729, P ≤ 0.05). A great number was caught in the rainy season (n = 329). In the dry season, 79 females were caught, which the fed females were twice greatest than the unfed. The length of gonotrophic cycle was estimated on the base of a high correlation coefficient value appearing every 4 days in rainy at 26.7 ± 1.22°C, and 3 days in dry season at 29.8 ± 1.47°C. The daily survival rate of the Ae. aegypti population was higher in both seasons, 0.94 and 0.93 for the rainy and dry season, respectively. The minimum time estimated for developing mature eggs after blood feeding was similar in both seasons (3.5 days in rainy versus 3.25 days in dry). The measurement of the vectorial capacity of Ae. aegypti in catholic churches could help to understand the dynamics of transmission of arboviruses in sites with high human aggregation.

  1. Host-seeking and blood-feeding behavior of Aedes albopictus (Diptera: Culicidae) exposed to vapors of geraniol, citral, citronellal, eugenol, or anisaldehyde.

    Science.gov (United States)

    Hao, Huiling; Wei, Jianrong; Dai, Jianqing; Du, Jiawei

    2008-05-01

    The changes of the host-seeking and blood-feeding behavior of Aedes albopictus (Skuse) (Diptera: Culicidae) surviving in a space containing vapors of the spatial repellents geraniol, eugenol, citral, anisaldehyde, or citronellal were evaluated using an arm-in-cage test and a bioassay of bloodmeals on a shaved mouse. The mosquitoes surviving concentrations of geraniol, citral, eugenol, or anisaldehyde at 0.013, 0.025, 0.050, 0.100, and 0.250 microg/cm3 for 24 and 48 h all showed different degrees of reduction in host-seeking ability. After 48 h of exposure to 0.250 microg/cm3 geraniol, almost 100% of the mosquitoes lost their host-seeking ability. The next most potent spatial repellent, anisaldehyde, stopped host seeking by > 85.5%. Citronellal did not result in a significant reduction in the host-seeking ability at any concentration level after either 24 or 48 h of treatment. We also found that reduction of host-seeking ability recovered after various times. The longest recovery time (144 h) was observed for geraniol after 24 h at 0.250 microg/cm3. In the study, geraniol, eugenol, and citral all significantly affected the activation and orientation stages of the blood-feeding behavior. However, only anisaldehyde significantly interrupted the normal blood-feeding of mosquitoes in all stages of behavior. These initial laboratory results clearly showed that anisaldehyde and geraniol could be promising spatial repellents against Ae. albopictus that they could play a major role in new repellent technology.

  2. Single dose of intra-muscular platelet rich plasma reverses the increase in plasma iron levels in exercise-induced muscle damage: A pilot study

    Directory of Open Access Journals (Sweden)

    Zekine Punduk

    2016-03-01

    Conclusion: Acute exhaustive exercise increased muscle damage markers, including plasma iron, IBC, and ferritin levels, indicating muscle damage induced by exercise. PRP administration improves inflammation by reversing the increase in the iron levels post-exercise without displaying any myotoxicity and may have a role to play in the recovery of exercise-induced muscle damage.

  3. Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, S.; Lyerly, D.L.; Pope, C.N.

    1992-01-01

    Organic solvants, as a class, have been implicated as neurotoxic agents in humans and laboratory animals. The study was designed to assess the interaction between subacute ingestion of moderate levels of ethanol and the p-xylene-induced decreases in protein and glycoprotein synthesis and axonal transport in the rat optic system. The results indicated that animals maintained on 10% ethanol as a drinking liquid show less p-xylene-induced neurotoxicity than animals receiving no ethanol supplement.

  4. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

    2016-05-15

    Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Tacrolimus reversibly reduces insulin secretion, induces insulin resistance, and causes islet cell damage in rats.

    Science.gov (United States)

    Xu, Chun; Niu, Yu-Jian; Liu, Xiao-Jun; Teng, Ya-Qin; Li, Chun-Feng; Wang, Hong-Yu; Yin, Jun-Ping; Wang, Le-Tian; Shen, Zhong-Yang

    2014-07-01

    To investigate the diabetogenic effects of the immunosuppressive agent tacrolimus, the reversibility of these effects upon treatment discontinuation, and the underlying mechanisms in a rat model. 60 healthy male rats were randomly divided into three groups for intragastric administration of tacrolimus either at 4 mg/kg/d or 2 mg/kg/d or an equal volume of normal saline (control). The treatment was administered for 5 months, followed by a 5-month period of no intervention. Fasting plasma glucose and insulin levels were used to calculate the homeostasis model assessment of ß-cell function (HOMA-ß) and insulin sensitivity index (ISI). Tacrolimus treatment significantly increased blood glucose concentrations (p insulin secretion pathway, local and/or systemic insulin resistance, and islet cell damage.

  6. A Case of Posterior Reversible Encephalopathy Syndrome Induced by Cisplatin/Pemetrexed Chemotherapy for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Masashi Ishihara

    2017-03-01

    Full Text Available This report presents the case of a 60-year-old woman who was diagnosed with stage IV lung adenocarcinoma with asymptomatic brain metastases and commenced chemotherapy with cisplatin/pemetrexed (CDDP/Pem. She experienced tonic-clonic convulsions on day 9 of the first cycle, which were accompanied by increased blood pressure (173/69 mm Hg and headache. Therefore, brain MRI was performed to check for stroke or progression of brain metastatic foci. T2-weighted, FLAIR, and ADC map images showed high-intensity areas in the subcortical region of the bilateral parieto-occipital lobes, leading to a diagnosis of posterior reversible encephalopathy syndrome (PRES. The symptoms improved after treatment with antihypertensive and antiepileptic drugs. Clinicians should keep it in mind that central nervous system symptoms during anticancer therapy containing Pem may indicate possible PRES.

  7. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice

    Science.gov (United States)

    Winters, B.; Mo, Z.; Brooks-Asplund, E.; Kim, S.; Shoukas, A.; Li, D.; Nyhan, D.; Berkowitz, D. E.

    2000-01-01

    Obesity is a major health care problem and is associated with significant cardiovascular morbidity. Leptin, a neuroendocrine hormone released by adipose tissue, is important in modulating obesity by signaling satiety and increasing metabolism. Moreover, leptin receptors are expressed on vascular endothelial cells (ECs) and mediate angiogenesis. We hypothesized that leptin may also play an important role in vasoregulation. We investigated vasoregulatory mechanisms in the leptin-deficient obese (ob/ob) mouse model and determined the influence of leptin replacement on endothelial-dependent vasorelaxant responses. The direct effect of leptin on EC nitric oxide (NO) production was also tested by using 4, 5-diaminofluorescein-2 diacetate staining and measurement of nitrate and nitrite concentrations. Vasoconstrictor responses to phenylephrine, norepinephrine, and U-46619 were markedly enhanced in aortic rings from ob/ob mice and were modulated by NO synthase inhibition. Vasorelaxant responses to ACh were markedly attenuated in mesenteric microvessels from ob/ob mice. Leptin replacement resulted in significant weight loss and reversal of the impaired endothelial-dependent vasorelaxant responses observed in ob/ob mice. Preincubation of ECs with leptin enhanced the release of NO production. Thus leptin-deficient ob/ob mice demonstrate marked abnormalities in vasoregulation, including impaired endothelial-dependent vasodilation, which is reversed by leptin replacement. These findings may be partially explained by the direct effect of leptin on endothelial NO production. These vascular abnormalities are similar to those observed in obese, diabetic, leptin-resistant humans. The ob/ob mouse may, therefore, be an excellent new model for the study of the cardiovascular effects of obesity.

  8. Chronic intrarenal insulin replacement reverses diabetes mellitus-induced natriuresis and diuresis.

    Science.gov (United States)

    Manhiani, M Marlina; Duggan, A Daniel; Wilson, Hunter; Brands, Michael W

    2012-02-01

    We showed recently that sustained natriuresis in type 1 diabetic dogs was attributed to the decrease in insulin rather than the hyperglycemia alone. The sodium-retaining action of insulin appeared to require hyperglycemia, and it completely reversed the diabetic natriuresis and diuresis. This study tested whether the sodium-retaining effect was attributed to direct intrarenal actions of insulin. Alloxan-treated dogs (D; n=7) were maintained normoglycemic using 24-h/d IV insulin replacement. After control measurements, IV insulin was decreased to begin a 6-day diabetic period. Blood glucose increased from 84±6 mg/dL to an average of 428 mg/dL on days 5 and 6, sodium excretion increased from 74±8 to 98±7 meq/d over the 6 days, and urine volume increased from 1645±83 to 2198±170 mL/d. Dir dogs (n=7) were subjected to the same diabetic regimen, but, in addition, insulin was infused continuously into the renal artery at 0.3 mU/kg per minute during the 6-day period. This did not affect plasma insulin. Blood glucose increased from 94±10 mg/dL to an average of 380 mg/dL on days 5 and 6, but sodium excretion averaged 76±5 and 69±8 meq/d during control and diabetes mellitus, respectively. The diuresis also was prevented. Glomerular filtration rate increased only in Dir dogs, and there was no change in mean arterial pressure in either group. This intrarenal insulin infusion had no effect on sodium or volume excretion in normal dogs. Intrarenal insulin replacement in diabetic dogs caused a sustained increase in tubular reabsorption that completely reversed diabetic natriuresis. Insulin plus glucose may work to prevent salt wasting in uncontrolled type 2 diabetes mellitus.

  9. Magnetization reversal induced by in-plane current in Ta/CoFeB/MgO structures with perpendicular magnetic easy axis

    Science.gov (United States)

    Zhang, C.; Yamanouchi, M.; Sato, H.; Fukami, S.; Ikeda, S.; Matsukura, F.; Ohno, H.

    2014-05-01

    We investigate in-plane current-induced magnetization reversal under an in-plane magnetic field in Hall bar shaped devices composed of Ta/CoFeB/MgO structures with perpendicular magnetic easy axis. The observed relationship between the directions of current and magnetization switching and Ta thickness dependence of magnetization switching current are accordance with those for magnetization reversal by spin transfer torque originated from the spin Hall effect in the Ta layer.

  10. Sexual functionality of Leptopilina clavipes (Hymenoptera: Figitidae) after reversing Wolbachia-induced parthenogenesis

    NARCIS (Netherlands)

    Pannebakker, BA; Schidlo, NS; Boskamp, GJF; Dekker, L; Van Dooren, TJM; Beukeboom, LW; Zwaan, BJ; Brakefield, PM; Van Alphen, JJM

    Females infected with parthenogenesis-inducing Wolbachia bacteria can be cured from their infection by antibiotic treatment, resulting in male production. In most cases, however, these males are either sexually not fully functional, or infected females have lost the ability to reproduce sexually. We

  11. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress

    NARCIS (Netherlands)

    van der Harg, J.M.; Nölle, A.; Zwart, R.; Boerema, A.S.; van Haastert, E.S.; Strijkstra, A.M.; Hoozemans, J.J.M.; Scheper, W.

    2014-01-01

    The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) in close connection with early stages of tau pathology. Metabolic disturbances are strongly associated with increased risk for AD and are a potent inducer of the UPR. Here, we

  13. Reversible acid-induced inactivation of the membrane fusion protein of Semliki Forest virus

    NARCIS (Netherlands)

    Waarts, BL; Smit, JM; Aneke, OJC; McInerney, GM; Liljestrom, P; Bittman, R; Wilschut, J

    Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific

  14. Further characterization of the reverse transcriptase associated with porcine (radiation-induced) retroviruses

    International Nuclear Information System (INIS)

    Frazier, M.E.; Mallavia, L.P.; Hooper, M.J.

    1980-01-01

    Differential centrifugation and affinity chromatography were used to purify the porcine, radiation-induced retrovirus, RNA-dependent DNA polymerase. The purified RDDP was taken differentiated from cellular DNA polymerase γ by its template specificity, chromatographic characteristics, and the optimum reaction conditions required for DNA synthesis

  15. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    Science.gov (United States)

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  16. Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

    Science.gov (United States)

    Blum, Jared; Carreiro, Stephanie; Hack, Jason B

    2013-10-01

    The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237

  17. Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

    Directory of Open Access Journals (Sweden)

    Katherine A Robinson

    Full Text Available Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1 plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway.

  18. Go-6976 Reverses Hyperglycemia-Induced Insulin Resistance Independently of cPKC Inhibition in Adipocytes

    Science.gov (United States)

    Robinson, Katherine A.; Hegyi, Krisztina; Hannun, Yusuf A.; Buse, Maria G.; Sethi, Jaswinder K.

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used “specific” inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not –β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

  19. Fast light-induced reversible wettability of a zinc oxide nanorod array coated with a thin gold layer

    Science.gov (United States)

    Wei, Yuefan; Du, Hejun; Kong, Junhua; Tran, Van-Thai; Koh, Jia Kai; Zhao, Chenyang; He, Chaobin

    2017-11-01

    Zinc oxide (ZnO) has gained much attention recently due to its excellent physical and chemical properties, and has been extensively studied in energy harvesting applications such as photovoltaic and piezoelectric devices. In recent years, its reversible wettability has also attracted increasing interest. The wettability of ZnO nanostructures with various morphologies has been studied. However, to the best of our knowledge, there is still a lack of investigations on further modifications on ZnO to provide more benefits than pristine ZnO. Comprehensive studies on the reversible wettability are still needed. In this study, a ZnO nanorod array was prepared via a hydrothermal process and subsequently coated with thin gold layers with varied thickness. The morphologies and structures, optical properties and wettability were investigated. It is revealed that the ZnO-Au system possesses recoverable wettability upon switching between visible-ultraviolet light and a dark environment, which is verified by the contact angle change. The introduction of the thin gold layer to the ZnO nanorod array effectively increases the recovery rate of the wettability. The improvements are attributed to the hierarchical structures, which are formed by depositing thin gold layers onto the ZnO nanorod array, the visible light sensitivity due to the plasmonic effect of the deposited gold, as well as the fast charge-induced surface status change upon light illumination or dark storage. The improvement is beneficial to applications in environmental purification, energy harvesting, micro-lenses, and smart devices.

  20. Temperature-induced sign reversal of biaxiality observed by conoscopy in some ferroelectric Sm-C* liquid crystals

    Science.gov (United States)

    Song, Jang-Kun; Chandani, A. D. L.; Fukuda, Atsuo; Vij, J. K.; Kobayashi, Ichiro; Emelyanenko, A. V.

    2007-07-01

    We have studied various ferroelectric liquid crystals to find the average molecular direction of the shortest axis in the perfectly unwound state by using tilted conoscopic measurements. We find that there exist two types of temperature dependencies of the biaxiality. Some materials exhibit increasing biaxiality while others show decreasing biaxiality with increasing temperature. The former shows a temperature-induced sign reversal of biaxiality. Three different physical mechanisms are identified as responsible for the emergence of biaxiality: (i) anisotropic fluctuations of the long molecular axis, (ii) a biased rotation around the long axis, and (iii) the local field effect. By means of a simple theoretical investigation, we conclude that these two types of trends are due mainly to the opposite signs of the biaxial order parameter C , which represents the second mechanism: the biased rotation around the long axis. This means that the central phenyl planes of molecules belonging to materials having biaxiality that increases with temperature are oriented on the average parallel to the tilt plane (the shortest index of refraction axis normal to the tilt plane), and, on the contrary, in those of the others molecules are oriented perpendicular to the tilt plane (the shortest index of refraction axis lying in the tilt plane). Thus, the direction of the phenyl ring plane of the liquid crystal molecules determines the different temperature dependencies of the biaxiality. It is also shown that the phenomenon of sign reversal of the biaxiality is due to the competitive contributions of the first and second physical mechanisms.

  1. Electrofluid hydrolysis enhances the production of fermentable sugars from corncob via in/reverse-phase induced voltage.

    Science.gov (United States)

    Wu, Fengfeng; Jin, Yamei; Li, Dandan; Zhou, Yuyi; Guo, Lunan; Zhang, Mengyue; Xu, Xueming; Yang, Na

    2017-06-01

    To improve the economic value of lignocellulosic biomasses, an innovative electrofluidic technology has been applied to the efficient hydrolysis of corncob. The system combines fluidic reactors and induced voltages via magnetoelectric coupling effect. The excitation voltage had a positive impact on reducing sugar content (RSC). But, the increase of voltage frequency at 400-700Hz caused a slight decline of the RSC. Higher temperature limits the electrical effect on the hydrolysis at 70-80°C. The energy efficiency increased under the addition of metallic ions and series of in-phase induced voltage to promote hydrolysis. In addition, the 4-series system with in-phase and reverse-phase induced voltages under the synchronous magnetic flux, exhibited a significant influence on the RSC with a maximum increase of 56%. High throughput could be achieved by increasing series in a compact system. Electrofluid hydrolysis avoids electrochemical reaction, electrode corrosion, and sample contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. How do Nutritional Stress and La Crosse Virus Infection Interact? Tests for Effects on Willingness to Blood Feed and Fecundity in Aedes albopictus (Diptera: Culicidae).

    Science.gov (United States)

    Westby, Katie M; Muturi, Ephantus J; Juliano, Steven A

    2016-01-01

    Evolutionary theory predicts that vector-borne pathogens should have low virulence for their vector because of selection against pathogens that harm the vector sufficiently to reduce transmission. Environmental factors such as nutritional stress can alter vector-pathogen associations by making the vectors more susceptible to pathogens (condition-dependent competence) and vulnerable to the harm caused by pathogen replication (condition-dependent virulence). We tested the hypotheses of condition-dependent competence and condition-dependent virulence by examining the interactive effects of short-term sugar deprivation and exposure to La Crosse virus (LACV) in female Aedes albopictus (Skuse). We predicted that infection status interacts with sugar deprivation to alter willingness to blood feed and fecundity in the second gonotrophic cycle (condition-dependent virulence). Sugar deprivation had no effect on body infection or disseminated infection rates. Infection status, sugar treatment, and their interaction had no effect on fecundity. Mosquitoes that had intermittent access to sugar were significantly more willing to take a second bloodmeal compared with those that had continuous access to sugar. Infection status and the interaction with sugar treatment had no effect on blood-feeding behavior. Thus, we found no evidence of short-term sugar deprivation leading to condition-dependent competence for, or condition-dependent virulence of, LACV in Ae. albopictus. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Efficacy of Blood Sources and Artificial Blood Feeding Methods in Rearing of Aedes aegypti (Diptera: Culicidae) for Sterile Insect Technique and Incompatible Insect Technique Approaches in Sri Lanka.

    Science.gov (United States)

    Gunathilaka, Nayana; Ranathunge, Tharaka; Udayanga, Lahiru; Abeyewickreme, Wimaladharma

    2017-01-01

    Selection of the artificial membrane feeding technique and blood meal source has been recognized as key considerations in mass rearing of vectors. Artificial membrane feeding techniques, namely, glass plate, metal plate, and Hemotek membrane feeding method, and three blood sources (human, cattle, and chicken) were evaluated based on feeding rates, fecundity, and hatching rates of Aedes aegypti . Significance in the variations among blood feeding was investigated by one-way ANOVA, cluster analysis of variance (ANOSIM), and principal coordinates (PCO) analysis. Feeding rates of Ae. aegypti significantly differed among the membrane feeding techniques as suggested by one-way ANOVA ( p feeding technique. Blood feeding rate of Ae. aegypti was higher with human blood followed by cattle and chicken blood, respectively. However, no significant difference was observed from the mosquitoes fed with cattle and human blood, in terms of fecundity, oviposition rate, and fertility as suggested by one-way ANOVA ( p > 0.05). Metal plate method could be recommended as the most effective membrane feeding technique for mass rearing of Ae. aegypti , due to its high feeding rate and cost effectiveness. Cattle blood could be recommended for mass rearing Ae. aegypti .

  4. The Influence of Insecticide Resistance, Age, Sex, and Blood Feeding Frequency on Thermal Tolerance of Wild and Laboratory Phenotypes of Anopheles funestus (Diptera: Culicidae).

    Science.gov (United States)

    Lyons, C L; Oliver, S V; Hunt, R H; Coetzee, M

    2016-03-01

    Resistance to insecticides is a global phenomenon and is increasing at an unprecedented rate. How resistant and susceptible strains of malaria vectors might differ in terms of life history and basic biology is often overlooked, despite the potential importance of such information in light of changing climates. Here, we investigated the upper thermal limits (ULT50) of wild and laboratory strains of Anopheles funestus Giles mosquitoes, including resistance status, sex, age, and blood feeding status as potential factors influencing ULT50. No significant differences in ULT50 were observed between strains displaying different resistance patterns, nor was there a significant difference between wild and laboratory strains. In some instances, strains showed a senescence response, displaying decreased ULT50 with an increase in age, and differences between males and females (females displaying higher ULT50 than males). Blood feeding did not seem to influence ULT50 in any way. For An. funestus, it seems evident that there is no cost to resistance despite what is displayed in other anopheline species. This could have significant impacts for vector control, with resistant populations of An. funestus performing just as well, if not better, than susceptible strains, especially under changing environmental conditions such as those expected to occur with climate change.

  5. Host species diversity and post-blood feeding carbohydrate availability enhance survival of females and fecundity in Aedes albopictus (Diptera: Culicidae).

    Science.gov (United States)

    Xue, Rui-De; Ali, Arshad; Barnard, Donald R

    2008-06-01

    Aedes albopictus mosquito is an opportunistic blood feeder and has a broad host range. The feeding behavior and habits of this mosquito are liable to increase the transmission potential of arboviruses. The survival and fecundity in A. albopictus fed on different hosts and post-blood meal provision of sugar were investigated in a laboratory-reared colony. Adult survival of caged female A. albopictus that were fed on blood of two different hosts (double meal) was higher than the females fed only on one host (single meal) (mean survival: 70.2+/-9.6 vs. 55.5+/-5.5%, respectively) when held in the laboratory for 72 h after blood feeding. Mean survival of females provided 10% sucrose solution (in water) after a single or double blood meal was higher (90.5+/-6.4% and 89.3+/-6.5%, respectively) than in the respective groups receiving water only following blood feeding (double meal: 49.0+/-9.6%; single meal: 45.3+/-10.9%). Females receiving a double meal were more fecund on average (89.0+/-6.6 eggs) than females provided a single meal (82.3+/-8.2 eggs).

  6. The inhibitory effect of a combination of imidacloprid and permethrin on blood feeding by mosquitoes in dogs raised under outdoor conditions.

    Science.gov (United States)

    Machida, Hiroyuki; Kondo, Tomoko; Kanehira, Katsushi; Hagimori, Ichiro; Kamio, Tsugihiko

    2008-07-04

    Combinations of imidacloprid and permethrin were frequently used to control harmful arthropod of companion animals. The inhibitory effects on blood-feeding activity of mosquitoes in dogs raised under outdoor conditions were evaluated by using combination of 10% (w/v) of imidacloprid and 50% (w/v) of permethrin as spot-on form. Dogs in the treated group received the combination imidacloprid/permethrin spot-on. After treatment, dogs in the control and treated groups were kept separately from the evening (17:00) to the morning of the following day (09:00) in two different kennels installed outdoors to mimic realistic dog-raising conditions. Mosquitoes in the kennels were collected by light traps placed in the kennels and a sweep net to determine evidence of blood feeding, and for species identification. Mosquitoes were collected at Days 5, 3 and 1 before agent treatment, and the Day of treatment, and Days 3, 7, 14, 21, 28, 35 and 42 after treatment. The percentages of blood-fed mosquitoes measured at Days 0, 3, 21, 28 and 42 after treatment were statistically significantly lower (pfeeding by adult female mosquitoes, and the efficacy lasts for 42 days after treatment under outdoor conditions.

  7. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    International Nuclear Information System (INIS)

    Xu, Xueqing; Chang, Bianca W.; Mans, Ben J.; Ribeiro, Jose M. C.; Andersen, John F.

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity

  8. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xueqing; Chang, Bianca W. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Mans, Ben J. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Agricultural Research Council, Onderstepoort 0110 (South Africa); Ribeiro, Jose M. C.; Andersen, John F., E-mail: jandersen@niaid.nih.gov [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States)

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.

  9. Ciguatoxin-induced catecholamine secretion in bovine chromaffin cells: mechanism of action and reversible inhibition by brevenal.

    Science.gov (United States)

    Nguyen-Huu, Truong D; Mattei, César; Wen, Peter J; Bourdelais, Andrea J; Lewis, Richard J; Benoit, Evelyne; Baden, Daniel G; Molgó, Jordi; Meunier, Frédéric A

    2010-10-01

    Ciguatoxin (P-CTX-1B) from the dinoflagellate Gambierdiscus toxicus, belongs to the family of polyether neurotoxins responsible for the neurological poisoning disorder ciguatera. Although it is the most widespread marine-borne disease affecting humans, there is no current FDA-approved treatment available except for symptomatic therapies. In this paper, we report that P-CTX-1B promotes catecholamine secretion from bovine chromaffin cells, an effect that is insensitive to concomitant activation of capacitative Ca(2+) entry. Moreover, we confirm that brevenal, a polyether from the dinoflagellate Karenia brevis, blocks P-CTX-1B-induced catecholamine secretion. This effect is partially reversible. Our results therefore raise the prospect of finding functional antagonists for P-CTX-1B that could be useful for the treatment of ciguatera. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

    DEFF Research Database (Denmark)

    Siersbæk, Majken; Varticovski, Lyuba; Yang, Shutong

    2017-01-01

    Abstract Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks...... of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers...... fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope...

  11. Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase.

    Science.gov (United States)

    Berg, Alexander K; Manokaran, Sumathra; Eiler, Daniel; Kooren, Joel; Mallik, Sanku; Srivastava, D K

    2008-01-01

    Peptide deformylase (PDF) catalyzes the removal of formyl group from the N-terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural-functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)-induced unfolding of the enzyme by monitoring the secondary structural changes via CD spectroscopy. The experimental data revealed that EcPDF is a highly stable enzyme, and it undergoes slow denaturation in the presence of varying concentrations of GdmCl. The most interesting aspect of these studies has been the abrupt reversal of the unfolding pathway at low to moderate concentrations of the denaturant, but not at high concentration. An energetic rationale for such an unprecedented feature in protein chemistry is offered.

  12. Reversal of Cellular Phenotypes in Neural Cells Derived from Huntington’s Disease Monkey-Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Richard L. Carter

    2014-10-01

    Full Text Available Huntington’s disease (HD is a dominant neurodegenerative disorder caused by the expansion of glutamine residues in the N-terminal region of the huntingtin (HTT protein. The disease results in progressive neuronal loss, leading to motor, cognitive, and psychiatric impairment. Here, we report the establishment of neural progenitor cell (NPC lines derived from induced pluripotent stem cells (iPSCs of transgenic HD monkeys. Upon differentiation to neurons, HD neural cells develop cellular features of HD, including the formation of nuclear inclusions and oligomeric mutant HTT (mHTT aggregates, as well as increased apoptosis. These phenotypes are rescued by genetic suppression of HTT and pharmacological treatment, demonstrating the ability of our HD cell model to respond to therapeutic treatment. The development and reversal of HD-associated phenotypes in neural cells from HD monkeys provides a unique nonhuman primate (NHP model for exploring HD pathogenesis and evaluating therapeutics that could be assessed further in HD monkeys.

  13. Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

    Directory of Open Access Journals (Sweden)

    Jeevan Kumar

    2012-01-01

    Full Text Available We report a case of bevacizumab- (BEV- induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

  14. Blockade and reversal of 5-methoxy-N,N-dimethyltryptamine-induced analgesia following noradrenaline depletion.

    Science.gov (United States)

    Archer, T; Minor, B G; Post, C

    1985-04-29

    The acute effects of the 5-hydroxytryptamine agonist, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. Noradrenaline depletion, following the systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 2 X 50 mg/kg, i.p.), caused a reversal of the analgesic effect of 5-MeO-DMT on shock-titration from hypo- to hypersensitivity, and a total blockade of the antinociceptive effect of 5-MeO-DMT upon pain responses in the hot-plate and tail-flick tests. Pretreatment with either p-chloroamphetamine (2 X 10 mg/kg) or p-chlorophenylalanine (200, 100, 100 mg/kg), that depletes central 5-hydroxytryptamine stores, failed to alter the analgesia caused by acute 5-MeO-DMT. Strong evidence is provided for the effect of central noradrenaline depletion upon the analgesic effect of the 5-HT agonist. These findings suggest an important tonic influence of the noradrenaline system upon the descending spinal 5-HT pathway in rats.

  15. A reversible pressure-induced phase transition in β-glycine at 0.76 GPa

    International Nuclear Information System (INIS)

    Goryainov, S.V.; Kolesnik, E.N.; Boldyreva, E.V.

    2005-01-01

    Single crystals of β-glycine were studied at pressures up to 7.6 GPa in a diamond anvil cell (DAC) in situ by Raman spectroscopy and polarized optical microscopy. A reversible phase transition was observed at 0.76 GPa. A boundary between the two phases could be observed in the microscope if the phase transition was slow enough. The phase transition was accompanied by cracking of the crystal. The birefringence in the high-pressure phase 2 was close to that in the starting phase 1, so that the phase transition can be supposed to preserve the monoclinic crystal system. Every vibrational band in the spectrum of the high-pressure phase can be related to a corresponding band in the starting phase, excluding lattice vibrations. The frequencies of most vibrations changed by a jump at the transition point. Low-frequency lattice modes showed linear pressure dependence when pressure increased from 0.76 to 7.6 GPa. This can be a manifestation of the softening of the libration modes of glycine at the phase transition point. At high pressures (in the range of 6.5-7.6 GPa) the shifts of the frequencies of some vibrational bands were nonlinear. This can be related to the rotations and twisting of the zwitter-ions of glycine

  16. Magnetized Reverse Shock: Density-fluctuation-induced Field Distortion, Polarization Degree Reduction, and Application to GRBs

    Energy Technology Data Exchange (ETDEWEB)

    Deng Wei; Zhang Bing [Department of Physics and Astronomy, University of Nevada Las Vegas, Las Vegas, NV 89154 (United States); Li Hui [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Stone, James M., E-mail: deng@physics.unlv.edu, E-mail: zhang@physics.unlv.edu, E-mail: hli@lanl.gov, E-mail: jstone@astro.princeton.edu [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544-1001 (United States)

    2017-08-10

    The early optical afterglow emission of several gamma-ray bursts (GRBs) shows a high linear polarization degree (PD) of tens of percent, suggesting an ordered magnetic field in the emission region. The light curves are consistent with being of a reverse shock (RS) origin. However, the magnetization parameter, σ , of the outflow is unknown. If σ is too small, an ordered field in the RS may be quickly randomized due to turbulence driven by various perturbations so that the PD may not be as high as observed. Here we use the “Athena++” relativistic MHD code to simulate a relativistic jet with an ordered magnetic field propagating into a clumpy ambient medium, with a focus on how density fluctuations may distort the ordered magnetic field and reduce PD in the RS emission for different σ values. For a given density fluctuation, we discover a clear power-law relationship between the relative PD reduction and the σ value of the outflow. Such a relation may be applied to estimate σ of the GRB outflows using the polarization data of early afterglows.

  17. Multi-resistive reduced graphene oxide diode with reversible surface electrochemical reaction induced carrier control.

    Science.gov (United States)

    Seo, Hyungtak; Ahn, Seungbae; Kim, Jinseo; Lee, Young-Ahn; Chung, Koo-Hyun; Jeon, Ki-Joon

    2014-07-10

    The extended application of graphene-based electronic devices requires a bandgap opening in order to realize the targeted device functionality. Since the bandgap tuning of pristine graphene is limited to 360 meV, the chemical modification of graphene is considered essential to achieve a large bandgap opening at the expense of electrical properties degradation. Reduced graphene oxide (RGO) has attracted significant interest for fabricating graphene-based semiconductors since it has several advantages over other forms of chemically modified graphene; such as tunable bandgap opening, decent electrical properties, and easy synthesis. Because of the reduced bonding nature of RGO, the role of metastable oxygen in the RGO matrix is recently highlighted and it may offer emerging ionic devices. In this study, we show that multi-resistivity RGO/n-Si diodes can be obtained by controlling the RGO thickness at a nanometer scale. This is made possible by (1) a metastable lattice-oxygen drift within bulk RGO and (2) electrochemical ambient hydroxyl (OH) formation at the RGO surface. The effect demonstrated in a p-RGO/n-Si heterojunction diode is equivalent to electrochemically driven reversible electronic manipulation and therefore provides an important basis for the application of O bistability in RGO for chemical sensors and electrocatalysis.

  18. Multisensory training reverses midbrain lesion-induced changes and ameliorates haemianopia.

    Science.gov (United States)

    Jiang, Huai; Stein, Barry E; McHaffie, John G

    2015-05-29

    Failure to attend to visual cues is a common consequence of visual cortex injury. Here, we report on a behavioural strategy whereby cross-modal (auditory-visual) training reinstates visuomotor competencies in animals rendered haemianopic by complete unilateral visual cortex ablation. The re-emergence of visual behaviours is correlated with the reinstatement of visual responsiveness in deep layer neurons of the ipsilesional superior colliculus (SC). This functional recovery is produced by training-induced alterations in descending influences from association cortex that allowed these midbrain neurons to once again transform visual cues into appropriate orientation behaviours. The findings underscore the inherent plasticity and functional breadth of phylogenetically older visuomotor circuits that can express visual capabilities thought to have been subsumed by more recently evolved brain regions. These observations suggest the need for reevaluating current concepts of functional segregation in the visual system and have important implications for strategies aimed at ameliorating trauma-induced visual deficits in humans.

  19. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    International Nuclear Information System (INIS)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young

    2008-01-01

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  20. Chlorfenapyr-induced toxic leukoencephalopathy with radiologic reversibility: A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Byung Hyun; Kim, Seul Kee; Yoon, Woong; Heo, Tae Wook; Lee, Yun Young [Dept. of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Kang, Heonung Keun [Dept. of Radiology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2016-04-15

    Chlorfenapyr is a widely used, moderately hazardous pesticide. Previous reports have indicated that chlorfenapyr intoxication can be fatal in humans. We reported the first non-fatal case of chlorfenapyr-induced toxic leukoencephalopathy in a 44-year-old female with resolution of extensive and abnormal signal intensities in white matter tracts throughout the brain, brain stem, and spinal cord on serial magnetic resonance imaging.

  1. Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

    OpenAIRE

    Shukla, Ruchi; Padhye, Subhash; Modak, Manisha; Ghaskadbi, Saroj S.; Bhonde, Ramesh R.

    2007-01-01

    Organic vanadium compounds offer several advantages in the treatment of diabetes, yet they are impractical to use because of known side effects. In order to ameliorate the side effects of vanadium, we conjugated it with quercetin to form bis(quercetinato)oxovanadium IV (BQOV). This study evaluates the effect of BQOV treatment on carbohydrate metabolism and overall oxidative stress in streptozotocin-induced (STZ) diabetic mice. Administration of BQOV orally to diabetic mice for 3 weeks led to ...

  2. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    2010-01-01

    Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

  3. Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

    Science.gov (United States)

    Han, Ren-wen; Zhang, Rui-san; Chang, Min; Peng, Ya-li; Wang, Pei; Hu, Sheng-quan; Choi, Chung-lit; Yin, Ming; Wang, Rui; Han, Yi-fan

    2012-08-27

    Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 μmol/kg), B7C (0.4-0.6 μmol/kg) or tacrine (8-12 μmol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Reverse effects of DPI administration combined with glutamine supplementation on function of rat neutrophils induced by overtraining.

    Science.gov (United States)

    Dong, Jingmei; Chen, Peijie; Liu, Qing; Wang, Ru; Xiao, Weihua; Zhang, Yajun

    2013-04-01

    To examine the excessive reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the combined effect of glutamine supplementation and diphenyleneiodonium (DPI) on the function of neutrophils induced by overtraining. Fifty male Wistar rats were randomly divided into 5 groups: control group (C), overtraining group (E), DPI-administration group (D), glutamine-supplementation group (G), and combined DPI and glutamine group (DG). Blood was sampled from the orbital vein after rats were trained on treadmill for 11 wk. Cytokine and lipid peroxidation in blood plasma were measured by enzyme-linked immunosorbent assay. The colocalization between gp91phox and p47phox of the NADPH oxidase was detected using immunocytochemistry and confocal microscopy. The activity of NADPH oxidase was assessed by chemiluminescence. Neutrophils' respiratory burst and phagocytosis function were measured by flow cytometry. NADPH oxidase was activated by overtraining. Cytokine and lipid peroxidation in blood plasma and the activity of NADPH oxidase were markedly increased in Group E compared with group C. Neutrophil function was lower in group E than group C. Both lower neutrophils function and higher ROS production were reversed in Group DG. The glutamine and DPI interference alone in group D and group G was less effective than DPI and glutamine combined in group DG. Activation of NADPH oxidase is responsible for the production of superoxide anions, which leads to excessive ROS and is related to the decrease in neutrophil function induced by overtraining. The combined DPI administration and glutamine supplementation reversed the decreased neutrophil function after overtraining.

  5. Anti-oxidative and anti-apoptotic roles of spermatogonial stem cells in reversing cisplatin-induced testicular toxicity.

    Science.gov (United States)

    Hussein, Yousri M; Mohamed, Randa H; Shalaby, Sally M; Abd El-Haleem, Manal R; Abd El Motteleb, Dalia M

    2015-11-01

    Because of reproductive toxic effects of chemotherapy, researchers have taken some techniques to preserve fertility potential. The present study was designed to point out the potential role of spermatogonial stem cell (SSC) therapy in reversing cisplatin (CP)-induced testicular toxicity and restore the spermatogenesis. Sixty rats were randomly divided into three groups: group 1, control group; group 2, rats received CP in a dose of 7 mg/kg/day for 5 consecutive days; group 3, CP was injected at 7 mg/kg per day for 5 consecutive days, and, on the 6th day of the experiment, rats were treated with SSC. Forty days after receiving the last dose of CP, rats were euthanized under anesthesia; testes were collected, and gene expression using real-time polymerase chain reaction for P53, Bax, caspase 9 and cytochrome c, testicular histological findings and oxidative status were determined. Administration of cisplatin caused significant increases in malondialdehyde levels, Bax and caspase 9 genes expression levels concomitant with significant decreases in anti-oxidant enzyme activities, p53 and cytochrome c gene expression levels, along with some histopathological lesions in testicular tissue. SCC attenuated the disturbance in oxidant/anti-oxidant status and testicular apoptosis; this is associated with improvements in the histopathological view of the testicular tissue. The current study highlights evidence that the SCC has anti-oxidative and anti-apoptotic properties that could reverse CP-induced testicular toxicity, in addition to their role in spermatogenesis. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. Ciprofloxacin-induced antibacterial activity is reversed by vitamin E and vitamin C.

    Science.gov (United States)

    Masadeh, Majed M; Mhaidat, Nizar M; Alzoubi, Karem H; Al-Azzam, Sayer I; Shaweesh, Ashraf I

    2012-05-01

    In the present study, we investigated the possible involvement of oxidative stress in ciprofloxacin-induced cytotoxicity against several reference bacteria including Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). Oxidative stress was assessed by measurement of hydrogen peroxide generation using a FACScan flow cytometer. The antibacterial activity of ciprofloxacin was assessed using the disk diffusion method and by measuring the minimum inhibitory concentration (MIC). Ciprofloxacin induced a dose-dependent antibacterial activity against all bacteria where the highest tested concentration was 100 ug/ml. Results revealed that E. coli cells were highly sensitive to ciprofloxacin (MIC = 0.21 μg/mL ± 0.087), P. aeruginosa and S. aureus cells were intermediately sensitive (MIC = 5.40 μg/mL ± 0.14; MIC = 3.42 μg/mL ± 0.377, respectively), and MRSA cells were highly resistant (MIC = 16.76 μg/mL ± 2.1). Pretreatment of E. coli cells with either vitamin E or vitamin C has significantly protected cells against ciprofloxacin-induced cytotoxicity. These results indicate the possible antagonistic properties for vitamins C or E when they are used concurrently with ciprofloxacin.

  7. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet.

    Science.gov (United States)

    Carillon, Julie; Jover, Bernard; Cristol, Jean-Paul; Rouanet, Jean-Max; Richard, Sylvain; Virsolvy, Anne

    2016-01-01

    Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD), have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate ( Cucumis melo L.) Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo . Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome-induced cardiovascular trouble.

  8. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2016-11-01

    Full Text Available Background: Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD, have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. Objective: We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. Design and results: The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L. Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Conclusions: Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble.

  9. 8-Modified-2'-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription.

    Directory of Open Access Journals (Sweden)

    Valérie Vivet-Boudou

    Full Text Available The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2'-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2'-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.

  10. Reversible DNA condensation induced by a tetranuclear nickel(II) complex.

    Science.gov (United States)

    Dong, Xindian; Wang, Xiaoyong; He, Yafeng; Yu, Zhen; Lin, Miaoxin; Zhang, Changli; Wang, Jing; Song, Yajie; Zhang, Yangmiao; Liu, Zhipeng; Li, Yizhi; Guo, Zijian

    2010-12-17

    DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [Ni(II)(4)(L-2H)(H(2)O)(6)(CH(3)CH(2)OH)(2)]·6NO(3) (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.291(9), b=24.15(2), c=13.896(11) Å, and β=98.175(13)°. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.

  11. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  12. Taurine Reverses Atrial Structural Remodeling in Ach-Cacl2Induced Atrial Fibrillation Rats.

    Science.gov (United States)

    Yang, Qunhui; Wu, Gaofeng; Han, Limei; Feng, Ying; Lin, Shumei; Lv, Qiufeng; Yang, Jiancheng; Hu, Jianmin

    2017-01-01

    Taurine has been reported to have anti-arrhythmia effects, but the anti-atrial fibrillation (AF) effects and its mechanism remain incompletely understood. In the present study, the therapy effects and partly mechanisms were investigated. AF animal model was established by intravenous administered with the mixture of acetylcholine (Ach) and CaCl 2 (66 μg/mL + 10 mg/mL) (i.v.) for 7 days. The actions of taurine (99 mg/kg∙d, introgastric administration) on the levels of Hs-CRP, IL-6, TNF-α, MMP-9, AngII, the extent of the fibrosis and ultrastructural changes in left atrial were studied. The data showed that the serum levels of TNF-α, IL-6, AngII and the plasma levels of Hs-CRP and MMP-9 were significantly elevated in automatic recovery group relative to the control group (p < 0.01), which were all decreased by taurine administration (p < 0.01) similar to Verapamil treatment. Masson's trichrome staining of the left atrial tissue showed an obvious interstitial fibrosis in rats of automatic recovery group. The alteration could be reversed by additional taurine. Electron microscopy revealed that taurine administration could significantly alleviate the ultrastructural damage of atrial cells, and the effects were similar to the Verapamil treatment. In conclusion, the results suggested that taurine could inhibit the structural remodeling of AF in rats partly by decreasing the levels of inflammatory factors and profibrotic molecules, attenuating the extent of myocardial fibrosis and protecting the integrity of myocardial ultrastructure.

  13. Lactate dehydrogenase inhibitors can reverse inflammation induced changes in colon cancer cells.

    Science.gov (United States)

    Manerba, Marcella; Di Ianni, Lorenza; Govoni, Marzia; Roberti, Marinella; Recanatini, Maurizio; Di Stefano, Giuseppina

    2017-01-01

    The inflammatory microenvironment is an essential component of neoplastic lesions and can significantly impact on tumor progression. Besides facilitating invasive growth, inflammatory cytokines were also found to reprogram cancer cell metabolism and to induce aerobic glycolysis. Previous studies did not consider the possible contribution played in these changes by lactate dehydrogenase (LDH). The A isoform of LDH (LDH-A) is the master regulator of aerobic glycolysis; it actively reduces pyruvate and causes enhanced lactate levels in tumor tissues. In cancer cells, lactate was recently found to directly increase migration ability; moreover, when released in the microenvironment, it can facilitate matrix remodeling. In this paper, we illustrate that treatment of human colon adenocarcinoma cells with TNF-α and IL-17, two pro-inflammatory cytokines, modifies LDH activity, causing a shift toward the A isoform which results in increased lactate production. At the same time, the two cytokines appeared to induce features of epithelial-mesenchymal transition in the treated cells, such as reduction of E-cadherin levels and increased secretion of metalloproteinases. Noteworthy, oxamate and galloflavin, two inhibitors of LDH activity which reduce lactate production in cells, were found to relieve the inflammation-induced effects. These results suggest LDH-A and/or lactate as common elements at the cross-road between cancer cell metabolism, tumor progression and inflammation. At present, LDH inhibitors suitable for clinical use are actively searched as possible anti-proliferative agents; our data lead to hypothesize for these compounds a wider potential in anticancer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

    Science.gov (United States)

    Kuge, Tomoo; Greenwood-Van Meerveld, Beverley; Sokabe, Masahiro

    2006-07-24

    Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function.

  15. Piroxicam Reverses Endotoxin-Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide

    Science.gov (United States)

    Buharalioglu, C. Kemal; Korkmaz, Belma; Cuez, Tuba; Sahan-Firat, Seyhan; Sari, Ayşe Nihal; Malik, Kafait U.; Tunctan, Bahar

    2011-01-01

    Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin-induced vascular hyporeactivity and hypotension resulting in multiple organ failure. Endotoxic shock is also characterized by decreased expression of constitutive cyclooxygenase (COX-1), cytochrome P450 (CYP) 4A and endothelial NOS (eNOS). Our previous studies demonstrated that dual inhibition of iNOS and COX with a selective COX-2 inhibitor, NS-398, or a non-selective COX inhibitor, indomethacin, restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from arachidonic acid (AA) by CYP4A in endotoxaemic rats. The aim of this study was to investigate the effects of piroxicam, a preferential COX-1 inhibitor, on the endotoxin-induced changes in blood pressure, expression of COX-1, inducible COX (COX-2), CYP4A1, eNOS, iNOS and heat shock protein 90 (hsp90), and production of PGI2, PGE2, 20-HETE and NO. Injection of endotoxin (10 mg/kg, i.p.) to male Wistar rats caused a fall in blood pressure and an increase in heart rate associated with elevated renal 6-keto-PGF1α and PGE2 levels as well as an increase in COX-2 protein expression. Endotoxin also caused an elevation in systemic and renal nitrite levels associated with increased renal iNOS protein expression. In contrast, systemic and renal 20-HETE levels and renal expression of eNOS, COX-1 and CYP4A1 were decreased in endotoxaemic rats. The effects of endotoxin, except for renal COX-1 and eNOS protein expression, were prevented by piroxicam (10 mg/kg, i.p.), given 1 hr after injection of endotoxin. Endotoxin did not change renal hsp90 protein expression. These data suggest that a decrease in the expression and activity of COX-2 and iNOS associated with an increase in CYP4A1 expression and 20-HETE synthesis contributes to the effect of piroxicam to prevent the hypotension during rat endotoxaemia. PMID:21463481

  16. Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering WNT signaling activity.

    Science.gov (United States)

    Chang, Ming-Kang; Kramer, Ina; Keller, Hansjoerg; Gooi, Jonathan H; Collett, Corinne; Jenkins, David; Ettenberg, Seth A; Cong, Feng; Halleux, Christine; Kneissel, Michaela

    2014-01-01

    The bone formation inhibitor sclerostin encoded by SOST binds in vitro to low-density lipoprotein receptor-related protein (LRP) 5/6 Wnt co-receptors, thereby inhibiting Wnt/β-catenin signaling, a central pathway of skeletal homeostasis. Lrp5/LRP5 deficiency results in osteoporosis-pseudoglioma (OPPG), whereas Sost/SOST deficiency induces lifelong bone gain in mice and humans. Here, we analyzed the bone phenotype of mice lacking Sost (Sost(-/-) ), Lrp5 (Lrp5(-/-) ), or both (Sost(-/-) ;Lrp5(-/-) ) to elucidate the mechanism of action of Sost in vivo. Sost deficiency-induced bone gain was significantly blunted in Sost(-/-) ;Lrp5(-/-) mice. Yet the Lrp5 OPPG phenotype was fully rescued in Sost(-/-) ;Lrp5(-/-) mice and most bone parameters were elevated relative to wild-type. To test whether the remaining bone increases in Sost(-/-) ;Lrp5(-/-) animals depend on Lrp6, we treated wild-type, Sost(-/-) , and Sost(-/-) ;Lrp5(-/-) mice with distinct Lrp6 function blocking antibodies. Selective blockage of Wnt1 class-mediated Lrp6 signaling reduced cancellous bone mass and density in wild-type mice. Surprisingly, it reversed the abnormal bone gain in Sost(-/-) and Sost(-/-) ;Lrp5(-/-) mice to wild-type levels irrespective of enhancement or blockage of Wnt3a class-mediated Lrp6 activity. Thus, whereas Sost deficiency-induced bone anabolism partially requires Lrp5, it fully depends on Wnt1 class-induced Lrp6 activity. These findings indicate: first, that OPPG syndrome patients suffering from LRP5 loss-of-function should benefit from principles antagonizing SOST/sclerostin action; and second, that therapeutic WNT signaling inhibitors may stop the debilitating bone overgrowth in sclerosing disorders related to SOST deficiency, such as sclerosteosis, van Buchem disease, and autosomal dominant craniodiaphyseal dysplasia, which are rare disorders without viable treatment options. © 2014 American Society for Bone and Mineral Research.

  17. Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation.

    Science.gov (United States)

    Blake, M G; Boccia, M M; Krawczyk, M C; Delorenzi, A; Baratti, C M

    2012-09-01

    It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8μg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Butyrate treatment reversed the UV light induced G1 checkpoint by increasing Histone H4 acetylation

    International Nuclear Information System (INIS)

    Koprinarova, M.; Markovska, P.; Botev, P.; Russev, G.

    2010-01-01

    HeLa cells were synchronized at the G1/S boundary with mimosine and were irradiated with 15 J.m -2 UV-C light. The cells were then released from the block and cultured in fresh media in the presence, or in the absence of sodium butyrate for four hours. The rate of DNA synthesis was determined by measuring the 3 H thymidine incorporation in DNA. In parallel series of experiments the levels of histone H4 acetylation were determined by Western blotting. We found out that UV irradiation of G1/S phase cells blocked their progression into S phase and that this was accompanied by a decrease of histone H4 acetylation. Butyrate was able to restore the levels of histone H4 acetylation, which was accompanied with a partial restoration of DNA synthesis. A conclusion was drawn that the UV light induced G1 checkpoint was executed by deacetylation of histone H4 in chromatin regions containing sequences important for DNA replication. Butyrate, which is a potent histone deacetylase inhibitor, blocks this reaction, which leads to restoration of the histone H4 acetylation and abrogation of the UV light induced G1 phase arrest. (authors)

  19. Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

    International Nuclear Information System (INIS)

    Underwood, S.R.; Walton, S.; Emanuel, R.W.; Swanton, R.H.; Campos Costa, D.; Laming, P.J.; Ell, P.J.

    1987-01-01

    Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean ΔRVEF+0.13 SD 0.099). Mean ΔRVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean ΔRVEF was -0.08 (SD 0.050). There was no significant correlation between ΔLVEF and ΔRVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography. (orig.)

  20. Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report

    Directory of Open Access Journals (Sweden)

    Rathi Shradha

    2007-11-01

    Full Text Available Abstract Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca chelation with fatty acids, producing enteric hyperoxaluria. Case A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier (normal 0.6–1.3 mg/dL. Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal Conclusion 1 High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2 The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3 Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.

  1. Reversible, non-plaque-induced loss of osseointegration of successfully loaded dental implants.

    Science.gov (United States)

    Mattheos, Nikos; Schittek Janda, Martin; Zampelis, Antonios; Chronopoulos, Vasilios

    2013-03-01

    Excess loading has been often cited as a reason for the failure of dental implants or bone loss post-osseointegration. The available data from animal studies have failed to show a clear role for excessive loading in the loss of osseointegration. The present case documentations aimed at providing a deeper insight into the medium- to long-term influence of occlusal loading on osseointegrated implants, and describe the clinical manifestations of such pathology. Two cases of loss of osseointegration are documented with single implants in the posterior maxilla. Implant mobility was in both cases the first and only sign of pathology, with the absence of plaque-induced inflammation and marginal bone loss. Re-osseointegration of the implants was achieved after the removal of the prosthetic reconstruction. The two cases reported that the loss of osseointegration in the absence of plaque-induced peri-implant inflammation is possible, although the clinical manifestations were very different to these of peri-implantitis. Once the occlusal loading was withdrawn, re-osseointegration was clinically confirmed in a period of 6-8 months. © 2012 John Wiley & Sons A/S.

  2. Reversing Coffee-Ring Effect by Laser-Induced Differential Evaporation.

    Science.gov (United States)

    Yen, Tony M; Fu, Xin; Wei, Tao; Nayak, Roshan U; Shi, Yuesong; Lo, Yu-Hwa

    2018-02-16

    The coffee-ring effect, ubiquitously present in the drying process of aqueous droplets, impedes the performance of a myriad of applications involving precipitation of particle suspensions in evaporating liquids on solid surfaces, such as liquid biopsy combinational analysis, microarray fabrication, and ink-jet printing, to name a few. We invented the methodology of laser-induced differential evaporation to remove the coffee-ring effect. Without any additives to the liquid or any morphology modifications of the solid surface the liquid rests on, we have eliminated the coffee-ring effect by engineering the liquid evaporation profile with a CO 2 laser irradiating the apex of the droplets. The method of laser-induced differential evaporation transitions particle deposition patterns from coffee-ring patterns to central-peak patterns, bringing all particles (e.g. fluorescent double strand DNAs) in the droplet to a designated area of 100 μm diameter without leaving any stains outside. The technique also moves the drying process from the constant contact radius (CCR) mode to the constant contact angle (CCA) mode. Physical mechanisms of this method were experimentally studied by internal flow tracking and surface evaporation flux mapping, and theoretically investigated by development of an analytical model.

  3. The phytoestrogen alpha-zearalenol reverses endothelial dysfunction induced by oophorectomy in rats.

    Science.gov (United States)

    Altavilla, D; Saitta, A; Galeano, M; Squadrito, G; Marino, D; Minutoli, L; Calapai, G; Deodato, B; D'Anna, R; Corrado, F; Caputi, A P; Squadrito, F

    2001-02-01

    It has been shown recently that alpha-zearalenol, a resorcyclic acid lactone, prevents bone loss in a rat model of postmenopausal bone loss. We have therefore investigated the effects of this phytoestrogen on endothelial dysfunction induced by estrogen deficiency in rats. Female mature Sprague-Dawley rats underwent a bilateral oophorectomy (OVX rats). Sham-operated animals (sham OVX rats) were used as controls. Three weeks after surgery, animals were randomized to the following treatments: alpha-zearalenol (1 mg/kg/day, i.m., for 4 weeks), 17beta-estradiol (20 microg/kg/day, i.m., for 4 weeks), or their vehicle (100 microl, i.m., of cottonseed oil). Two other groups of rats were treated with alpha-zearalenol or 17beta-estradiol plus the pure estrogen receptor antagonist ICI 182780 (2.5 mg/kg/day, i.m., for 4 weeks). Mean arterial blood pressure (MAP), heart rate (HR), total plasma cholesterol, plasma estradiol, and plasma alpha-zearalenol were studied. We also investigated endothelial-dependent (acetylcholine, 10 nM to 10 microM) and endothelial-independent (sodium nitroprusside, 15 nM to 30 nM) relaxation of aortic rings, as well as N(G)-methyl-L-arginine (L-NMA: 10 to 100 microM)-induced vasoconstriction and calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX rats and OVX rats. Untreated OVX rats had, compared with sham OVX animals, unchanged body weight, MAP, HR, and plasma cholesterol. In contrast oophorectomy reduced plasma estradiol levels (OVX, 2 +/- 0.5 pg/ml; sham OVX, 35 +/- 6 pg/ml), impaired endothelial-dependent relaxation and blunted L-NMA-induced contraction (L-NMA 100 microM: sham OVX, 2.7 +/- 0.3 g/mg tissue; OVX, 1.3 +/- 0.1 g/mg tissue). Moreover OVX rats showed a reduced calcium-dependent NO synthase (cNOS) activity. Treatment with alpha-zearalenol or with 17beta-estradiol reverted the endothelial dysfunction and increased cNOS activity in lung homogenates. These effects were abolished by the

  4. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects

    Directory of Open Access Journals (Sweden)

    Nisar MS

    2013-05-01

    Full Text Available Mahrukh S Nisar,1 Karthik Iyer,1 Robert T Brodell,2 Jenifer R Lloyd,3 Thuzar M Shin,3 Asad Ahmad4 1Northeast Ohio Medical University, Rootstown, OH, USA; 2Division of Dermatology, University of Mississippi Medical Center, Jackson, MS, USA; 3Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Northside Medical Center, Youngstown, OH, USA Abstract: Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG 1064 nm, Alexandrite 755 nm, and Ruby 694 nm were used in test areas. The Alexandrite 755 nm

  5. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

    DEFF Research Database (Denmark)

    Ansel, L; Bentsen, A H; Ancel, C

    2011-01-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic...... stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity...... of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase...

  6. Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa

    International Nuclear Information System (INIS)

    Tielemans, Y.; Chen, D.; Sundler, F.; Haakanson, R.; Willems, G.

    1992-01-01

    Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. The authors studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, wheras it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa. 33 refs., 6 figs

  7. Ginkgo biloba leaf extract reverses amyloid beta-peptide-induced isoprostane production in rat brain in vitro.

    Science.gov (United States)

    Brunetti, Luigi; Orlando, Giustino; Menghini, Luigi; Ferrante, Claudio; Chiavaroli, Annalisa; Vacca, Michele

    2006-11-01

    Isoprostanes are prostaglandin (PG) isomers generated from oxygen radical peroxidation of arachidonic acid, which are reliable markers of membrane oxidative damage. Aging is characterized by an imbalance between the generation of reactive oxygen species and antioxidant detoxification pathways. Ginkgo biloba leaf extract is reputed as a neuroprotective antioxidant agent. We have tested the effects of a Ginkgo biloba extract {containing 24.1 % flavonoids and 181 % terpene lactones [bilobalide (0.542 %), ginkgolide A (0.570 %), ginkgolide B (0.293 %), ginkgolide C (0.263 %), and ginkgolide J (0.138 %)]} on the production of 8-iso-PGF2alpha from rat brain synaptosomes obtained from young (3 months old) or aged (12 and 24 months old) rats, both in the basal state and after oxidative stress induced by either hydrogen peroxide or amyloid beta-peptide. Our findings show that Ginkgo biloba extract pretreatment is able to completely reverse both basal and hydrogen peroxide-stimulated isoprostane production (IC50 of 81.92 microM and 31.89 microM, respectively). Amyloid beta-peptide-induced isoprostane production was also inhibited, both in young and aged rats, to a level even lower than that in unstimulated synaptosomes. This suggests that the oxygen radical scavenging properties of the Ginkgo biloba extract are fully effective in young, as well as in old rats, showing a greater inhibition of isoprostane production in the latter.

  8. Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Galat, Yekaterina; Perepitchka, Mariana; Jennings, Lawrence J.; Iannaccone, Philip M.; Hendrix, Mary J.C.

    2016-01-01

    Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID:27193052

  9. Sialotranscriptomics of Rhipicephalus zambeziensis reveals intricate expression profiles of secretory proteins and suggests tight temporal transcriptional regulation during blood-feeding.

    Science.gov (United States)

    de Castro, Minique Hilda; de Klerk, Daniel; Pienaar, Ronel; Rees, D Jasper G; Mans, Ben J

    2017-08-10

    Ticks secrete a diverse mixture of secretory proteins into the host to evade its immune response and facilitate blood-feeding, making secretory proteins attractive targets for the production of recombinant anti-tick vaccines. The largely neglected tick species, Rhipicephalus zambeziensis, is an efficient vector of Theileria parva in southern Africa but its available sequence information is limited. Next generation sequencing has advanced sequence availability for ticks in recent years and has assisted the characterisation of secretory proteins. This study focused on the de novo assembly and annotation of the salivary gland transcriptome of R. zambeziensis and the temporal expression of secretory protein transcripts in female and male ticks, before the onset of feeding and during early and late feeding. The sialotranscriptome of R. zambeziensis yielded 23,631 transcripts from which 13,584 non-redundant proteins were predicted. Eighty-six percent of these contained a predicted start and stop codon and were estimated to be putatively full-length proteins. A fifth (2569) of the predicted proteins were annotated as putative secretory proteins and explained 52% of the expression in the transcriptome. Expression analyses revealed that 2832 transcripts were differentially expressed among feeding time points and 1209 between the tick sexes. The expression analyses further indicated that 57% of the annotated secretory protein transcripts were differentially expressed. Dynamic expression profiles of secretory protein transcripts were observed during feeding of female ticks. Whereby a number of transcripts were upregulated during early feeding, presumably for feeding site establishment and then during late feeding, 52% of these were downregulated, indicating that transcripts were required at specific feeding stages. This suggested that secretory proteins are under stringent transcriptional regulation that fine-tunes their expression in salivary glands during feeding. No open

  10. The gelatinous extracellular matrix facilitates transport studies in kelp: visualization of pressure-induced flow reversal across sieve plates.

    Science.gov (United States)

    Knoblauch, Jan; Peters, Winfried S; Knoblauch, Michael

    2016-04-01

    In vascular plants, important questions regarding phloem function remain unanswered due to problems with invasive experimental procedures in this highly sensitive tissue. Certain brown algae (kelps; Laminariales) also possess sieve tubes for photoassimilate transport, but these are embedded in large volumes of a gelatinous extracellular matrix which isolates them from neighbouring cells. Therefore, we hypothesized that kelp sieve tubes might tolerate invasive experimentation better than their analogues in higher plants, and sought to establish Nereocystis luetkeana as an experimental system. The predominant localization of cellulose and the gelatinous extracellular matrix in N. luetkeana was verified using specific fluorescent markers and confocal laser scanning microscopy. Sieve tubes in intact specimens were loaded with fluorescent dyes, either passively (carboxyfluorescein diacetate; CFDA) or by microinjection (rhodamine B), and the movement of the dyes was monitored by fluorescence microscopy. Application of CFDA demonstrated source to sink bulk flow in N. luetkeana sieve tubes, and revealed the complexity of sieve tube structure, with branches, junctions and lateral connections. Microinjection into sieve elements proved comparatively easy. Pulsed rhodamine B injection enabled the determination of flow velocity in individual sieve elements, and the direct visualization of pressure-induced reversals of flow direction across sieve plates. The reversal of flow direction across sieve plates by pressurizing the downstream sieve element conclusively demonstrates that a critical requirement of the Münch theory is satisfied in kelp; no such evidence exists for tracheophytes. Because of the high tolerance of its sieve elements to experimental manipulation, N. luetkeana is a promising alternative to vascular plants for studying the fluid mechanics of sieve tube networks. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company

  11. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  12. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Science.gov (United States)

    Balakrishnan, Mini; Yant, Stephen R; Tsai, Luong; O'Sullivan, Christopher; Bam, Rujuta A; Tsai, Angela; Niedziela-Majka, Anita; Stray, Kirsten M; Sakowicz, Roman; Cihlar, Tomas

    2013-01-01

    HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA) integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly.

  13. Trachyspermum ammi Seeds Supplementation Helps Reverse Scopolamine, Alprazolam and Electroshock Induced Amnesia.

    Science.gov (United States)

    Soni, Kapil; Parle, Milind

    2017-05-01

    The present study was designed to explore the beneficial effects of successive 10 days administration of Trachyspermum ammi seed's powder (TASP) along with diet (at the dose of 0.5%, 1.0% and 2.0% w/w) on learning and memory of mice. A total of 306 mice divided in 51 equal groups were employed in the study. Passive avoidance paradigm (PAP) and Object recognition Task (ORT) were employed as exteroceptive models. The brain acetylcholinesterase activity (AChE), serum cholesterol, brain monoaldehyde (MDA), brain reduced glutathione (GSH) and brain nitrite were estimated and Alprazolam, Scopolamine and Electroshock induced amnesia was employed to describe the actions. Treatment of TASP significantly increased step down latency of PAA and significantly increased discrimination index of ORT in groups with or without amnesia when compared to respective control groups. Furthermore, TASP administration resulted in significant fall in brain AChE activity, brain MDA level and brain nitrite level with simultaneous rise in brain GSH level, thereby decreased oxidative damage. A significant decrease in serum cholesterol was also observed. Ajowan supplementation may prove a remedy for the management of cognitive disorders owing to have pro-cholinergic, antioxidant and hypo-lipidemic activities.

  14. Lepidium meyenii (Maca) reversed the lead acetate induced -- damage on reproductive function in male rats.

    Science.gov (United States)

    Rubio, Julio; Riqueros, Marissa I; Gasco, Manuel; Yucra, Sandra; Miranda, Sara; Gonzales, Gustavo F

    2006-07-01

    Rats were treated with 0, 8, 16 and 24 mg/kg of lead acetate (LA) (i.p.) for 35 days with or without Maca. Maca was co-administrated orally from day 18 to day 35. The lengths of stages of the seminiferous epithelium were assessed by transillumination. Also, sex organ weights, testicular and epididymal sperm count, sperm motility, daily sperm production, sperm transit rate and serum testosterone levels were measured. Lead acetate treatment resulted in a dose-response reduction of lengths of stages VIII and IX-XI, and serum testosterone levels. However, rats treated with 8 and 16 mg/kg but not 24 mg/kg of lead acetate showed a low number of testicular spermatids, low daily sperm production (DSP) and low epididymal sperm count. Administration of Maca to rats treated with lead acetate resulted in higher lengths of stages VIII and IX-XI with respect to lead acetate-treated rats. Moreover, treatment with Maca to lead acetate-treated rats resulted in lengths of stages VIII and IX-XI similar to the control group. Maca administration also reduced the deleterious effect on DSP caused by lead acetate treatment. Maca prevented LA-induced spermatogenic disruption in rats and it may become in a potential treatment of male infertility associated with lead exposure.

  15. Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function

    Science.gov (United States)

    Zhou, Luyi; Sun, Wei-Lun; Young, Amy B.; Lee, Kunhee; McGinty, Jacqueline F.

    2015-01-01

    Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. PMID:25539504

  16. Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

    Directory of Open Access Journals (Sweden)

    Jin Yong Kang

    2016-01-01

    Full Text Available The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT (7.1 μg/kg of body weight; intraperitoneal injection was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh levels increased, whereas the activity of acetylcholinesterase (AChE decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA content, an increase in the oxidized glutathione (GSH ratio, and a decline of total superoxide dismutase (SOD level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404.

  17. Inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer.

    Science.gov (United States)

    Li, Yuehua; Jiang, Baohong; Zhu, Hongbo; Qu, Xiaofei; Zhao, Liqin; Tan, Yeru; Jiang, Yiling; Liao, Mingchu; Wu, Xiaoping

    2017-06-01

    proliferation, invasion, and migration in the siROR + Tamoxifen group were much decreased; these results implied that downregulated long non-coding RNA ROR suppressed BT474 cell proliferation, invasion, and migration and reversed the effect of Tamoxifen on the BT474 cells. These results indicate that inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer.

  18. A yeast strain for simultaneous detection of induced mitotic crossing over, mitotic gene conversion and reverse mutation

    International Nuclear Information System (INIS)

    Zimmermann, F.K.; Kern, R.; Rasenberger, H.

    1975-01-01

    A diploid yeast strain of Saccharomyces cerevisiae is described which can be used to study induction of mitotic crossing-over, mitotic gene conversion and reverse mutation. Mitotic crossing-over can be detected visually as pink and red twin-sectored colonies which are due to the formation of homozygous cells of the genotype ade2-40/ade2-40 (deep red) and ade-2-119/ade2-119 (pink) from the originally heteroallelic condition ade2-40/ade2-119 which forms white colonies. Mitotic gene conversion is monitored by the appearance of tryptophan nonrequiring colonies on selective media. The alleles involved are trp5-12 and trp5-27 derived from the widely used strain D 4 . Mutation induction can be followed by the appearance of isoleucine nonrequiring colonies on selective media. D 7 is homoallelic ilvI-92. The isoleucine requirement caused by ilvI-92 can be alleviated by true reverse mutation and allele non-specific suppressor mutation. The effects of ethyl methanesulfonate (EMS), nitrous acid, ultraviolet light and hycanthone methanesulfonate were studied with D 7 stationary phase cells. Mitotic crossing-over as monitored by red/pink twin-sectored colonies was almost equally frequent among normal and convertant cells. This showed again that nitotic recombination is not due to the presence of a few cells committed to meiosis in an otherwise mitotic cell population. The dose-response curves for induction of mitotic gene conversion and reversion of the isoleucine requirement were exponential. In contrast to this, the dose-response curve for induction of twin sectored red and pink colonies reached a plateau at doses giving about 30% cell killing. This could partly be due to lethal segregation in the progeny of treated cells. None of the agents tested would induce only one type of mitotic recombination, gene conversion or crossing-over. There was, however, some mutagen specificity in the induction of isoleucine prototrophs

  19. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease.

    Directory of Open Access Journals (Sweden)

    Peter G Traber

    Full Text Available Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan or GM-CT-01 (galactomannan. In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip or GM-CT-01 (180 mg/kg ip given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis.

  20. Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia.

    Science.gov (United States)

    Hsu, Chao-Yu; Hung, Ching-Sui; Chang, Hung-Ming; Liao, Wen-Chieh; Ho, Shih-Chun; Ho, Ying-Jui

    2015-04-01

    Glutamatergic hyperactivity plays an important role in the pathophysiology of Parkinson's disease (PD). Ceftriaxone increases expression of glutamate transporter 1 (GLT-1) and affords neuroprotection. This study was aimed at clarifying whether ceftriaxone prevented, or reversed, behavioral and neuronal deficits in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Male Wistar rats were injected daily with either ceftriaxone starting 5 days before or 3 days after MPTP lesioning (day 0) or saline and underwent a bar-test on days 1-7, a T-maze test on days 9-11, and an object recognition test on days 12-14, then the brains were taken for histological evaluation on day 15. Dopaminergic degeneration in the substantia nigra pars compacta and striatum was observed on days 3 and 15. Motor dysfunction in the bar test was observed on day 1, but disappeared by day 7. In addition, lesioning resulted in deficits in working memory in the T-maze test and in object recognition in the object recognition task, but these were not observed in rats treated pre- or post-lesioning with ceftriaxone. Lesioning also caused neurodegeneration in the hippocampal CA1 area and induced glutamatergic hyperactivity in the subthalamic nucleus, and both changes were suppressed by ceftriaxone. Increased GLT-1 expression and its co-localization with astrocytes were observed in the striatum and hippocampus in the ceftriaxone-treated animals. To our knowledge, this is the first study showing a relationship between ceftriaxone-induced GLT-1 expression, neuroprotection, and improved cognition in a PD rat model. Ceftriaxone may have clinical potential for the prevention and treatment of dementia associated with PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Growth hormone reverses excitotoxic damage induced by kainic acid in the green iguana neuroretina.

    Science.gov (United States)

    Ávila-Mendoza, José; Mora, Janeth; Carranza, Martha; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) is expressed in extrapituitary tissues, including the nervous system and ocular tissues, where it is involved in autocrine/paracrine actions related to cell survival and anti-apoptosis in several vertebrates. Little is known, however, in reptiles, so we analyzed the expression and distribution of GH in the eye of green iguana and its potential neuroprotective role in retinas that were damaged by the intraocular administration of kainic acid (KA). It was found, by Western blotting, that GH-immunoreactivity (GH-IR) was expressed as two isoforms (15 and 26kDa, under reducing conditions) in cornea, vitreous, retina, crystalline, iris and sclera, in varying proportions. Also, two bands for the growth hormone receptor (GHR)-IR were observed (70 and 44kDa, respectively) in the same tissues. By immunofluorescence, GH-IR was found in neurons present in several layers of the neuroretina (inner nuclear [INL], outer nuclear [ONL] and ganglion cell [GCL] layers) as determined by its co-existence with NeuN, but not in glial cells. In addition, GH and GHR co-expression was found in the same cells, suggesting paracrine/autocrine interactions. KA administration induced retinal excitotoxic damage, as determined by a significant reduction of the cell density and an increase in the appearance of apoptotic cells in the INL and GCL. In response to KA injury, both endogenous GH and Insulin-like Growth Factor I (IGF-I) expression were increased by 70±1.8% and 33.3±16%, respectively. The addition of exogenous GH significantly prevented the retinal damage produced by the loss of cytoarchitecture and cell density in the GCL (from 4.9±0.79 in the control, to 1.45±0.2 with KA, to 6.35±0.49cell/mm(2) with KA+GH) and in the INL (19.12±1.6, 10.05±1.9, 21.0±0.8cell/mm(2), respectively) generated by the long-term effect of 1mM KA intraocular administration. The co-incubation with a specific anti-GH antibody, however, blocked the protective effect of GH

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

    Science.gov (United States)

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

    2015-02-01

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

  3. Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Shukla, Ruchi; Padhye, Subhash; Modak, Manisha; Ghaskadbi, Saroj S; Bhonde, Ramesh R

    2007-01-01

    Organic vanadium compounds offer several advantages in the treatment of diabetes, yet they are impractical to use because of known side effects. In order to ameliorate the side effects of vanadium, we conjugated it with quercetin to form bis(quercetinato)oxovanadium IV (BQOV). This study evaluates the effect of BQOV treatment on carbohydrate metabolism and overall oxidative stress in streptozotocin-induced (STZ) diabetic mice. Administration of BQOV orally to diabetic mice for 3 weeks led to a reduction of blood glucose levels and the animals exhibited normal glucose tolerance at the end of the study period. The increase in glucose uptake by skeletal muscle and liver as well as the normalization of mRNA levels of G-6-Pase and glucokinase in the liver after BQOV treatment pointed to improvements in carbohydrate metabolism. The analysis of the antioxidant status of serum, liver and pancreas revealed reduced oxidative stress in BQOV-treated animals compared to untreated diabetic controls. Serum analyses for kidney and liver function showed that BQOV treatment provoked total protection of the kidney and partial protection of the liver from diabetogenic insults. The number of insulin-positive cells and the amount of pancreatic insulin in treated mice (1.2038 +/- 0.34 ng/mg tissue) did not account for pancreatic regeneration but suggested an insulin-mimetic action on the part of BQOV. Moreover, administration of BQOV for 3 weeks did not show any visible side-effects. This data indicate that BQOV is a safe and potent agent for diabetes treatment, because it is able to improve carbohydrate metabolism and to reduce overall oxidative stress.

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

    Science.gov (United States)

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

    2016-02-16

    -inflammatory M2 phenotype and reduces activation of astrocytes in hyperammonemic rats. This reduces neuroinflammation, normalizes membrane expression of glutamate and GABA receptors, and restores spatial learning in hyperammonemic rats. Hyperammonemia-induced neuroinflammation impairs glutamatergic and GABAergic neurotransmission by altering membrane expression of glutamate and GABA receptors, resulting in impaired spatial learning. Sulforaphane reverses all these effects. Treatment with sulforaphane could be useful to improve cognitive function in cirrhotic patients with minimal or clinical hepatic encephalopathy.

  5. Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

    Science.gov (United States)

    Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

    2013-02-15

    The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Efficacy of Blood Sources and Artificial Blood Feeding Methods in Rearing of Aedes aegypti (Diptera: Culicidae for Sterile Insect Technique and Incompatible Insect Technique Approaches in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Nayana Gunathilaka

    2017-01-01

    Full Text Available Introduction. Selection of the artificial membrane feeding technique and blood meal source has been recognized as key considerations in mass rearing of vectors. Methodology. Artificial membrane feeding techniques, namely, glass plate, metal plate, and Hemotek membrane feeding method, and three blood sources (human, cattle, and chicken were evaluated based on feeding rates, fecundity, and hatching rates of Aedes aegypti. Significance in the variations among blood feeding was investigated by one-way ANOVA, cluster analysis of variance (ANOSIM, and principal coordinates (PCO analysis. Results. Feeding rates of Ae. aegypti significantly differed among the membrane feeding techniques as suggested by one-way ANOVA (p0.05. Conclusions. Metal plate method could be recommended as the most effective membrane feeding technique for mass rearing of Ae. aegypti, due to its high feeding rate and cost effectiveness. Cattle blood could be recommended for mass rearing Ae. aegypti.

  7. Implementation of all-optical reversible logic gate based on holographic laser induced grating using azo-dye doped polymers

    Science.gov (United States)

    Forsati, Rana; Valipour Ebrahimi, Sara; Navi, Keivan; Mohajerani, Ezeddin; Jashnsaz, Hossein

    2013-02-01

    Increasing demand for power reduction in computer systems has led to new trends in computations and computer design including reversible computing. Its main aim is to eliminate power dissipation in logical elements but can have some other advantages such as data security and error prevention. Because of interesting properties of reversible computing, implementing computing devices with reversible manner is the only way to make the reversible computing a reality. In recent years, reversible logic has turned out to be a promising computing paradigm having application in CMOS, nanotechnology, quantum computing and optical computing. In this paper, we propose and realize a novel implementation of Toffoli gate in all-optical domain. We have explained its principle of operations and described an actual experimental implementation. The all-optical reversible gate presented in this paper will be useful in different applications such as arithmetic and logical operations in the domain of reversible logic-based computing.

  8. Nitrogen remobilisation facilitates adventitious root formation on reversible dark-induced carbohydrate depletion in Petunia hybrida.

    Science.gov (United States)

    Zerche, Siegfried; Haensch, Klaus-Thomas; Druege, Uwe; Hajirezaei, Mohammad-Reza

    2016-10-10

    Adventitious root (AR) formation in axillary shoot tip cuttings is a crucial physiological process for ornamental propagation that is utilised in global production chains for young plants. In this process, the nitrogen and carbohydrate metabolisms of a cutting are regulated by its total nitrogen content (N t ), dark exposure during transport and irradiance levels at distinct production sites and phases through a specific plasticity to readjust metabolite pools. Here, we examined how elevated N t contents with a combined dark exposure of cuttings influence their internal N-pools including free amino acids and considered early anatomic events of AR formation as well as further root development in Petunia hybrida cuttings. Enhanced N t contents of unrooted cuttings resulted in elevated total free amino acid levels and in particular glutamate (glu) and glutamine (gln) in leaf and basal stem. N-allocation to mobile N-pools increased whereas the allocation to insoluble protein-N declined. A dark exposure of cuttings conserved initial N t and nitrate-N, while it reduced insoluble protein-N and increased soluble protein, amino- and amide-N. The increase of amino acids mainly comprised asparagine (asn), aspartate (asp) and arginine (arg) in the leaves, with distinct tissue specific responses to an elevated N supply. Dark exposure induced an early transient rise of asp followed by a temporary increase of glu. A strong positive N effect of high N t contents of cuttings on AR formation after 384 h was observed. Root meristematic cells developed at 72 h with a negligible difference for two N t levels. After 168 h, an enhanced N t accelerated AR formation and gave rise to first obvious fully developed roots while only meristems were formed with a low N t . However, dark exposure for 168 h promoted AR formation particularly in cuttings with a low N t to such an extent so that the benefit of the enhanced N t was almost compensated. Combined dark exposure and low N t of

  9. Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.

    Science.gov (United States)

    Zahlten, Janine; Kim, Ye-Ji; Doehn, Jan-Moritz; Pribyl, Thomas; Hocke, Andreas C; García, Pedro; Hammerschmidt, Sven; Suttorp, Norbert; Hippenstiel, Stefan; Hübner, Ralf-Harto

    2015-06-01

    Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. During pneumococcal pneumonia, the human airway epithelium is exposed to large amounts of H2O2 as a product of host and pathogen oxidative metabolism. Airway cells are known to be highly vulnerable to oxidant damage, but the pathophysiology of oxidative stress induced by S. pneumoniae and the role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant systems of the host are not well characterized. For gluthation/gluthathion disulfide analysis BEAS-2B cells, primary broncho-epithelial cells (pBEC), explanted human lung tissue and mouse lungs were infected with different S. pneumoniae strains (D39, A66, R6x, H2O2/pneumolysin/LytA- deficient mutants of R6x). Cell death was proven by LDH assay and cell viability by IL-8 ELISA. The translocation of Nrf2 and the expression of catalase were shown via Western blot. The binding of Nrf2 at the catalase promoter was analyzed by ChIP. We observed a significant induction of oxidative stress induced by S. pneumoniae in vivo, ex vivo, and in vitro. Upon stimulation, the oxidant-responsive transcription factor Nrf2 was activated, and catalase was upregulated via Nrf2. The pneumococci-induced oxidative stress was independent of S. pneumoniae-derived H2O2 and pneumolysin but depended on the pneumococcal autolysin LytA. The Nrf2 inducer resveratrol, as opposed to catalase, reversed oxidative stress in lung epithelial cells. These observations indicate a H2O2-independent induction of oxidative stress in lung epithelial cells via the release of bacterial factors of S. pneumoniae. Resveratrol might be an option for prevention of acute lung injury and inflammatory responses observed in pneumococcal pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

    Science.gov (United States)

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-01-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  11. AP-2α reverses vincristine-induced multidrug resistance of SGC7901 gastric cancer cells by inhibiting the Notch pathway.

    Science.gov (United States)

    Lian, Wei; Zhang, Li; Yang, Long; Chen, Wensheng

    2017-07-01

    Multidrug resistance (MDR) remains a major clinical obstacle in the treatment of gastric cancer (GC) since it causes tumor recurrence and metastasis. The transcription factor activator protein-2α (AP-2α) has been implicated in drug-resistance in breast cancer; however, its effects on MDR of gastric cancer are far from understood. In this study, we aimed to explore the effects of AP-2α on the MDR in gastric cancer cells selected by vincristine (VCR). Decreased AP-2α levels were markedly detected by RT-PCR and Western blot in gastric cancer cell lines (BGC-823, SGC-7901, AGS, MKN-45) compared with that in the gastric epithelial cell line (GES-1). Furthermore, we found that the expression of AP-2α in SGC7901/VCR or SGC7901/adriamycin (ADR) cells was lower than in SGC7901 cells. Thus, a vector overexpressing AP-2α was constructed and used to perform AP-2α gain-of-function studies in SGC7901/VCR cells. The decreased IC50 values of the anti-cancer drugs in sensitive and resistant cells after transfect with pcDNA3.1/AP-2α were determined in SGC7901/VCR cells by MTT assay. Moreover, flow cytometry analysis indicated that overexpressed AP-2α induced cell cycle arrest in the G0/G1 phase and promoted cell apoptosis of VCR-selected SGC7901/VCR cells. RT-PCR and Western blot demonstrated that overexpressed AP-2α can significantly induce the down-regulation of Notch1, Hes-1, P-gp and MRP1 in SGC7901/VCR cells. Similar effects can be observed when Numb (Notch inhibitor) was introduced. In addition, the intracellular ADR accumulation was markedly detected in AP-2α overexpressed or Numb cells. In conclusion, our results indicate that AP-2α can reverse the MDR of gastric cancer cells, which may be realized by inhibiting the Notch signaling pathway.

  12. Trifluoperazine-Induced Suicidal Erythrocyte Death and S-Nitrosylation Inhibition, Reversed by the Nitric Oxide Donor Sodium Nitroprusside

    Directory of Open Access Journals (Sweden)

    Mehrdad Ghashghaeinia

    2017-08-01

    Full Text Available Background and Purpose: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl-propyl]-2-(trifluoromethyl-(10H-phenothiazine dihydrochloride; TFP may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i and inhibited by nitric oxide (NO. We explored whether TFP treatment of erythrocytes induces phosphatidylserine exposure, cell shrinkage, and calcium influx, whether it impairs S-nitrosylation and whether these effects are inhibited by NO. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and protein nitrosylation from fluorescence switch of the Bodipy-TMR/Sypro Ruby signal. Results: Exposure of human erythrocytes to TFP significantly enhanced the percentage of annexin-V-binding cells, raised [Ca2+]i, and decreased S-nitrosylation. The effect of TFP on annexin-V-binding was not affected by removal of extracellular Ca2+ alone, but was significantly inhibited by pre-treatment with sodium nitroprusside (SNP, an effect significantly augmented by additional removal of extracellular Ca2+. A 3 hours treatment with 0.1 µM Ca2+ ionophore ionomycin triggered annexin-V-binding and cell shrinkage, effects fully reversed by removal of extracellular Ca2+. Conclusions: TFP induces eryptosis and decreases protein S-nitrosylation, effects blunted by nitroprusside. The effect of nitroprusside is attenuated in the presence of extracellular Ca2+.

  13. Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

    2015-01-01

    Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period. PMID:26617490

  14. A trypsin inhibitor from rambutan seeds with antitumor, anti-HIV-1 reverse transcriptase, and nitric oxide-inducing properties.

    Science.gov (United States)

    Fang, Evandro Fei; Ng, Tzi Bun

    2015-04-01

    Nephelium lappaceum L., commonly known as "rambutan," is a typical tropical tree and is well known for its juicy and sweet fruit which has an exotic flavor. Chemical studies on rambutan have led to the identification of various components such as monoterpene lactones and volatile compounds. Here, a 22.5-kDa trypsin inhibitor (N . lappaceum trypsin inhibitor (NLTI)) was isolated from fresh rambutan seeds using liquid chromatographical techniques. NLTI reduced the proteolytic activities of both trypsin and α-chymotrypsin. Dithiothreitol reduced the trypsin inhibitory activity of NLTI at a concentration of 1 mM, indicating that an intact disulfide bond is essential to the activity. NLTI inhibited HIV-1 reverse transcriptase with an IC50 of 0.73 μM. In addition, NLTI manifested a time- and dose-dependent inhibitory effect on growth in many tumor cells. NLTI is one of the few trypsin inhibitors with nitric oxide-inducing activity and may find application in tumor therapy.

  15. Amino acid infusions induce reversible, dose-related decreases in bile flow in the isolated rat liver.

    Science.gov (United States)

    Shattuck, K E; Grinnell, C D; Rassin, D K

    1993-01-01

    Parenteral infusion of amino acid solutions is known to produce cholestasis in experimental animal models and in the isolated perfused rat liver. To characterize the dose responsiveness and reversibility of amino acid-induced cholestasis, isolated rat livers were perfused with solutions containing 1.5, 3.0, or 6.0 g of amino acids for 1 hour and allowed to recover for 30 minutes. Perfusion of livers resulted in a rapid, dose-related decrease in bile flow (p < .0001 at doses of 3.0 and 6.0 g). When the amino acid solution was discontinued, bile flow recovered to near control rates. Infusion of taurocholate reduced the magnitude of the decrease in bile flow associated with amino acid infusion but did not prevent it. Infusion of amino acid solutions was associated with the following changes in bile: (1) dose-related increases in total free amino acid concentrations; (2) increased osmolarity; (3) increased glucose concentrations; (4) increased potassium concentrations; (5) decreased chloride concentrations; (6) increased oxygen uptake in livers not perfused with added taurocholate; and (7) increased total bile acid concentrations in livers perfused with added taurocholate. Additional investigations are needed to determine whether these associations are attributable to individual amino acids or the total metabolic load of the amino acids.

  16. L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.

    Science.gov (United States)

    Nguyen, Long T; Stangenberg, Stefanie; Chen, Hui; Al-Odat, Ibrahim; Chan, Yik L; Gosnell, Martin E; Anwer, Ayad G; Goldys, Ewa M; Pollock, Carol A; Saad, Sonia

    2015-04-01

    Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences. Copyright © 2015 the American Physiological Society.

  17. Dynamical Time-Reversal Symmetry Breaking and Photo-Induced Chiral Spin Liquid in Frustrated Mott Insulators

    Science.gov (United States)

    Claassen, Martin; Jiang, Hong-Chen; Moritz, Brian; Devereaux, Thomas

    Spurred by recent progress in melting, enhancement and induction of electronic order out of equilibrium, a tantalizing prospect concerns instead accessing transient Floquet steady states via broad pump pulses, to manipulate band topology and affect electronic transport. Here, we extend these ideas to strongly-correlated systems and show that pumping frustrated Mott insulators with circularly-polarized light can drive the effective spin system across a phase transition to a chiral spin liquid (CSL). Starting from a Kagome Hubbard model deep in the Mott phase, circular polarization promotes a scalar spin chirality Si . (Sj ×Sk) term directly to the Hamiltonian level, dynamically breaking time-reversal while preserving SU(2) spin symmetry. We find that the transient physics is well-captured by an effective Floquet spin model, fingerprint its phase diagram, and find a stable photo-induced CSL in close proximity to the equilibrium state. The results presented suggest a new avenue of employing dynamical symmetry breaking to engineer quantum spin liquids and access elusive phase transitions that are not readily accessible in equilibrium.

  18. Reversible superconductor-insulator transition in LiTi2O4 induced by Li-ion electrochemical reaction.

    Science.gov (United States)

    Yoshimatsu, K; Niwa, M; Mashiko, H; Oshima, T; Ohtomo, A

    2015-11-06

    Transition metal oxides display various electronic and magnetic phases such as high-temperature superconductivity. Controlling such exotic properties by applying an external field is one of the biggest continuous challenges in condensed matter physics. Here, we demonstrate clear superconductor-insulator transition of LiTi2O4 films induced by Li-ion electrochemical reaction. A compact electrochemical cell of pseudo-Li-ion battery structure is formed with a superconducting LiTi2O4 film as an anode. Li content in the film is controlled by applying a constant redox voltage. An insulating state is achieved by Li-ion intercalation to the superconducting film by applying reduction potential. In contrast, the superconducting state is reproduced by applying oxidation potential to the Li-ion intercalated film. Moreover, superconducting transition temperature is also recovered after a number of cycles of Li-ion electrochemical reactions. This complete reversible transition originates in difference in potentials required for deintercalation of initially contained and electrochemically intercalated Li(+) ions.

  19. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points - An international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

    DEFF Research Database (Denmark)

    Puhringer, F.K.; Rex, C.; Sielenkamper, A.W.

    2008-01-01

    Background: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evalua...

  20. Temperature-induced sex reversal is not responsible for sex-ratio distortions in grayling Thymallus thymallus or brown trout Salmo trutta.

    Science.gov (United States)

    Pompini, M; Buser, A M; Thali, M R; Von Siebenthal, B A; Nusslé, S; Guduff, S; Wedekind, C

    2013-08-01

    On the basis of the experiments carried out over various years, it was concluded that (1) grayling Thymallus thymallus and brown trout Salmo trutta are resistant to temperature-induced sex reversal at ecologically relevant temperatures, (2) environmental sex reversal is unlikely to cause the persistent sex ratio distortion observed in at least one of the study populations and (3) sex-specific tolerance of temperature-related stress may be the cause of distorted sex ratios in populations of T. thymallus or S. trutta. © 2013 The Fisheries Society of the British Isles.

  1. Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.

    Science.gov (United States)

    Rabien, Anja; Stephan, Carsten; Kilic, Ergin; Weichert, Wilko; Kristiansen, Glen; Miller, Kurt; Jung, Klaus; Erbersdobler, Andreas

    2013-10-16

    Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study. Tumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray. RECK strongly decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon signed rank test, P<0.001), and it discriminated tumor entities showing the highest expression in oncocytomas. EMMPRIN, however, could be significantly correlated to pT stage and Fuhrman grading (Spearman's correlation coefficient rs=0.289 and rs=0.382, respectively). Higher expression of EMMPRIN was associated with decreased overall survival in Kaplan-Meier analysis (P<0.001), and the EMMPRIN level could independently predict survival for cases without metastasis and involvement of lymph nodes. Decreased RECK expression was confirmed by Western blotting in tissue of eight normal/tumor matches of patients after radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous. We propose RECK down regulation in renal cell carcinoma to be an early event that facilitates tumor formation and progression. EMMPRIN, however, as a prognostic tumor marker, increases only when aggressiveness is proceeding and could add an additional step to invasive properties of renal cell carcinoma.

  2. In situ atomic force microscopy studies of reversible light-induced switching of surface roughness and adhesion in azobenzene-containing PMMA films

    International Nuclear Information System (INIS)

    Mueller, M.; Gonzalez-Garcia, Y.; Pakula, C.; Zaporojtchenko, V.; Strunskus, T.; Faupel, F.; Herges, R.; Zargarani, D.; Magnussen, O.M.

    2011-01-01

    Thin films in the range 40-80 nm of a blend of PMMA with an azobenzene derivative have been studied directly during UV and blue light irradiation by atomic force microscopy (AFM), revealing highly reversible changes in the surface roughness and the film adhesion. UV light induces an ∼80% increase in surface roughness, whereas illumination by blue light completely reverses these changes. Based on the observed surface topography and transition kinetics a reversible mass flow mechanisms is suggested, where the polarity changes upon switching trigger a wetting-dewetting transition in a surface segregation layer of the chromophore. Similar AFM measurements of the pull-off force indicate a decrease upon UV and an increase after blue light illumination with a complex kinetic behavior: a rapid initial change, attributed to the change in the cis isomer fraction of the azobenzene derivative, and a more gradual change, indicative of slow structural reorganization.

  3. Magnetic compensation-induced sign reversal of exchange bias in a multi-glass perovskite SmFeO3

    Science.gov (United States)

    De, Chandan; Nayak, Ajaya K.; Nicklas, Michael; Sundaresan, A.

    2017-10-01

    We report an unusual sign reversal of exchange bias (EB) across a magnetic compensation point in an orthorhombic perovskite SmFeO3. A conventional negative EB with a positive vertical magnetization shift is observed below a cluster-glass freezing temperature (Tg ˜ 150 K). Upon further lowering of the temperature, the EB disappears at the magnetic compensation point before reversing its sign to a positive exchange bias below 4 K. The EB effect originates from an interfacial exchange interaction within a cluster glass phase, whereas its sign reversal arises from the reversal of the direction of the net magnetic moment as a result of dominance of Sm3+ over Fe3+ below the compensation temperature. The existence of a multi-glass state is demonstrated by ac-susceptibility and electrical permittivity measurements. A phenomenological model is presented to understand the EB effect and its sign reversal across the compensation point.

  4. 7-Fluoro-1,3-diphenylisoquinoline reverses motor and non-motor symptoms induced by MPTP in mice: Role of striatal neuroinflammation.

    Science.gov (United States)

    Sampaio, Tuane Bazanella; Marcondes Sari, Marcel Henrique; Pesarico, Ana Paula; Mantovani, Anderson Carboni; Zeni, Gilson; Nogueira, Cristina Wayne

    2018-01-15

    Parkinson's disease (PD) is a dopaminergic neurodegenerative disorder, which presents motor and non-motor symptoms. 7-Fluoro-1,3-diphenylisoquinoline (FDPI) is an isoquinoline compound with antioxidant and antidepressant properties. This study investigated whether FDPI reverses motor and non-motor symptoms in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was also assessed the anti-inflammatory mechanisms in FDPI pharmacological action. C57Bl/6 male adult mice received four MPTP (20mg/kg, intraperitoneal) or saline (vehicle) injections to induce an acute PD model. FDPI (10mg/kg, intragastric) was daily administered to mice from the 2nd to 9th day after the induction and mice performed the behavioral tests on the 8th and 9th days. Striatum samples were collected for biochemical and molecular analyses. The results of the rotarod and challenging beam tests demonstrated that the administration of FDPI attenuated the impairments in balance and coordination of mice induced by MPTP. The FDPI reversed the short-term memory deficit and depressive-like behavior induced by MPTP in mice. FDPI attenuated the reduction in the striatal tyrosine hydroxylase levels, and it reversed the increase in the cyclooxygenase-2 levels and myeloperoxidase activity caused by MPTP in mice. Therefore, FDPI reversed motor and non-motor symptoms induced by an acute PD model and its restorative effects seem to be mediated by an anti-inflammatory action associated with a modulation of the striatal cyclooxygenase-2 levels and myeloperoxidase activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Exogenous hydrogen peroxide reversibly inhibits root gravitropism and induces horizontal curvature of primary root during grass pea germination.

    Science.gov (United States)

    Jiang, Jinglong; Su, Miao; Wang, Liyan; Jiao, Chengjin; Sun, Zhengxi; Cheng, Wei; Li, Fengmin; Wang, Chongying

    2012-04-01

    During germination in distilled water (dH(2)O) on a horizontally positioned Petri dish, emerging primary roots of grass pea (Lathyrus sativus L.) grew perpendicular to the bottom of the Petri dish, due to gravitropism. However, when germinated in exogenous hydrogen peroxide (H(2)O(2)), the primary roots grew parallel to the bottom of the Petri dish and asymmetrically, forming a horizontal curvature. Time-course experiments showed that the effect was strongest when H(2)O(2) was applied prior to the emergence of the primary root. H(2)O(2) failed to induce root curvature when applied post-germination. Dosage studies revealed that the frequency of primary root curvature was significantly enhanced with increased H(2)O(2) concentrations. This curvature could be directly counteracted by dimethylthiourea (DMTU), a scavenger of H(2)O(2), but not by diphenylene iodonium (DPI) and pyridine, inhibitors of H(2)O(2) production. Exogenous H(2)O(2) treatment caused both an increase in the activities of H(2)O(2)-scavenging enzymes [including ascorbate peroxidase (APX: EC 1.11.1.11), catalase (CAT: EC 1.11.1.6) and peroxidase (POD: EC 1.11.1.7)] and a reduction in endogenous H(2)O(2) levels and root vitality. Although grass pea seeds absorbed exogenous H(2)O(2) during seed germination, DAB staining of paraffin sections revealed that exogenous H(2)O(2) only entered the root epidermis and not inner tissues. These data indicated that exogenously applied H(2)O(2) could lead to a reversible loss of the root gravitropic response and a horizontal curvature in primary roots during radicle emergence of the seedling. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  6. Chronic administration of modafinil induces hyperalgesia in mice: reversal by L-NG-nitro-arginine methyl ester and 7-nitroindazole.

    Science.gov (United States)

    Gupta, Rachna; Gupta, Lalit Kumar; Bhattacharya, Swapan K

    2014-08-05

    Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of pain in mice. Also, this study evaluated the effect of L-NG-nitroarginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and naloxone following chronic administration of modafinil. Modafinil was administered in the doses of 50, 100 or 200 mg/kg once in acute study and it showed significantly increased tail-flick latency (tfl) and paw-licking latency. In formalin test modafinil (100 mg/kg) significantly reduced licking/biting time in both early and late phases in comparison to control. In chronic study, modafinil 100 mg/kg administered for 10 days, produced a progressive decrease in the reaction time (i.e., tfl/paw-licking latency) in comparison to day 1 values which started building up from day 4 and fully established at day 6, indicating hyperalgesic response. Prior administration of 7-NI (on day 7) and L-NAME (on day 10) prevented the hyperalgesic response while naloxone on day 10 did not have a significant effect on modafinil-induced hyperalgesia. These results demonstrate that modafinil has a potential role in pain as it exhibited antinociceptive effect after acute administration in a dose-dependent manner and on chronic administration it caused hyperalgesia. This hyperalgesia is reversed by nitric oxide synthase inhibitors, suggesting the possibility of involvement of nitric oxide pathway. Further studies are required to evaluate the role of modafinil in clinical pain. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high-fat diet and ovariectomy in mice.

    Science.gov (United States)

    Ohtake, Kazuo; Ehara, Nobuyuki; Chiba, Hiroshige; Nakano, Genya; Sonoda, Kunihiro; Ito, Junta; Uchida, Hiroyuki; Kobayashi, Jun

    2017-04-01

    Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect on this syndrome. We examined the effect of dietary nitrite in a mouse model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) and a high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF with or without sodium nitrite (50 mg and 150 mg/l) in the drinking water. Daily food intake and weekly body weight were monitored for 18 wk. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and mice developed obesity with visceral hypertrophic adipocytes and increased transcriptional levels of monocyte chemoattractant protein-1, TNF-α, and IL-6 in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose-dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that an endogenous NO defect might underlie postmenopausal metabolic syndrome and that dietary nitrite provides an alternative source of NO, subsequently compensating for metabolic impairments of this syndrome. Copyright © 2017 the American Physiological Society.

  8. An Inhaled Inhibitor of Myristoylated Alanine-Rich C Kinase Substrate Reverses LPS-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Yin, Qi; Fang, Shijing; Park, Joungjoa; Crews, Anne L; Parikh, Indu; Adler, Kenneth B

    2016-11-01

    Intratracheal instillation of bacterial LPS is a well-established model of acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Because the myristoylated alanine-rich C kinase substrate (MARCKS) protein is involved in neutrophil migration and proinflammatory cytokine production, we examined whether an aerosolized peptide that inhibits MARCKS function could attenuate LPS-induced lung injury in mice. The peptide, BIO-11006, was delivered at 50 μM via inhalation either just before intratracheal instillation of 5 μg of LPS into Balb/C mice, or 4, 12, 24, or 36 hours after LPS instillation. Effects of BIO-11006 were evaluated via analysis of mouse disease-related behavior, lung histology, bronchoalveolar lavage fluid total protein, neutrophil counts and percentages, cytokine (KC [CXCl1, mouse IL-8 equivalent] and TNF-α) expression, and activation of NF-κB in lung tissue. Treatment with aerosolized BIO-11006 at 0, 4, 12, 24, and even 36 hours after LPS instillation reversed the disease process: mouse behavior returned to normal after two treatments 12 hours apart with the inhaled peptide after LPS injury, whereas control LPS-instilled animals treated with PBS only remained moribund. Histological appearance of inflammation, bronchoalveolar lavage fluid protein levels, leukocyte and neutrophil numbers, KC and TNF-α gene and protein expression, and NF-κB activation were all significantly attenuated by inhaled BIO-11006 at all time points. These results implicate MARCKS protein in the pathogenesis of ALI/ARDS and suggest that MARCKS-inhibitory peptide(s), delivered by inhalation, could represent a new and potent therapeutic treatment for ALI/ARDS, even if administered well after the disease process has begun.

  9. Structural study of the AOT reverse micellar system. Influence of attractive interactions induced by the solubilisation of native and modified proteins

    International Nuclear Information System (INIS)

    Cassin, Guillaume

    1994-01-01

    This research thesis reports the study of the influence of intra-micellar attractions on the thermodynamic behaviour of reverse micellar systems, as well as of the effects induced by the solubilisation of natives or modified proteins. The author proposes a model to explain the decrease of attractions between droplets when the volume fraction occupied by reverse micelles increases. This model which highlights the importance of depletion forces between reverse micelles, allows the building up of a theoretical relationship between the bonding parameter and the volume fraction of reverse micelles. In order to understand the appearance of an attractive term related to the solubilisation of native cytochrome-c in these systems, this protein has been chemically modified. The author highlights the role of the charge born by a micellar probe on the thermodynamic behaviour of micro-emulsions. Then, the author applies the model of dimerizing adhesive spheres to reverse micellar systems containing native cytochrome-c. He shows that theoretical predictions of this model are in agreement with obtained experimental results [fr

  10. Glucocorticoid-induced reversal of interleukin-1β-stimulated inflammatory gene expression in human oviductal cells.

    Directory of Open Access Journals (Sweden)

    Stéphanie Backman

    Full Text Available Studies indicate that high-grade serous ovarian carcinoma (HGSOC, the most common epithelial ovarian carcinoma histotype, originates from the fallopian tube epithelium (FTE. Risk factors for this cancer include reproductive parameters associated with lifetime ovulatory events. Ovulation is an acute inflammatory process during which the FTE is exposed to follicular fluid containing both pro- and anti-inflammatory molecules, such as interleukin-1 (IL1, tumor necrosis factor (TNF, and cortisol. Repeated exposure to inflammatory cytokines may contribute to transforming events in the FTE, with glucocorticoids exerting a protective effect. The global response of FTE cells to inflammatory cytokines or glucocorticoids has not been investigated. To examine the response of FTE cells and the ability of glucocorticoids to oppose this response, an immortalized human FTE cell line, OE-E6/E7, was treated with IL1β, dexamethasone (DEX, IL1β and DEX, or vehicle and genome-wide gene expression profiling was performed. IL1β altered the expression of 47 genes of which 17 were reversed by DEX. DEX treatment alone altered the expression of 590 genes, whereas combined DEX and IL1β treatment altered the expression of 784 genes. Network and pathway enrichment analysis indicated that many genes altered by DEX are involved in cytokine, chemokine, and cell cycle signaling, including NFκΒ target genes and interacting proteins. Quantitative real time RT-PCR studies validated the gene array data for IL8, IL23A, PI3 and TACC2 in OE-E6/E7 cells. Consistent with the array data, Western blot analysis showed increased levels of PTGS2 protein induced by IL1β that was blocked by DEX. A parallel experiment using primary cultured human FTE cells indicated similar effects on PTGS2, IL8, IL23A, PI3 and TACC2 transcripts. These findings support the hypothesis that pro-inflammatory signaling is induced in FTE cells by inflammatory mediators and raises the possibility that

  11. The entomopathogenic fungus Beauveria bassiana reduces instantaneous blood feeding in wild multi-insecticide-resistant Culex quinquefasciatus mosquitoes in Benin, West Africa

    Directory of Open Access Journals (Sweden)

    Howard Annabel FV

    2010-09-01

    Full Text Available Abstract Background Mosquito-borne diseases are still a major health risk in many developing countries, and the emergence of multi-insecticide-resistant mosquitoes is threatening the future of vector control. Therefore, new tools that can manage resistant mosquitoes are required. Laboratory studies show that entomopathogenic fungi can kill insecticide-resistant malaria vectors but this needs to be verified in the field. Methods The present study investigated whether these fungi will be effective at infecting, killing and/or modifying the behaviour of wild multi-insecticide-resistant West African mosquitoes. The entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were separately applied to white polyester window netting and used in combination with either a permethrin-treated or untreated bednet in an experimental hut trial. Untreated nets were used because we wanted to test the effect of fungus alone and in combination with an insecticide to examine any potential additive or synergistic effects. Results In total, 1125 female mosquitoes were collected during the hut trial, mainly Culex quinquefasciatus Say. Unfortunately, not enough wild Anopheles gambiae Giles were collected to allow the effect the fungi may have on this malaria vector to be analysed. None of the treatment combinations caused significantly increased mortality of Cx. quinquefasciatus when compared to the control hut. The only significant behaviour modification found was a reduction in blood feeding by Cx. quinquefasciatus, caused by the permethrin and B. bassiana treatments, although no additive effect was seen in the B. bassiana and permethrin combination treatment. Beauveria bassiana did not repel blood foraging mosquitoes either in the laboratory or field. Conclusions This is the first time that an entomopathogenic fungus has been shown to reduce blood feeding of wild mosquitoes. This behaviour modification indicates that B. bassiana could potentially be a new

  12. Evaluation of a simple polytetrafluoroethylene (PTFE)-based membrane for blood-feeding of malaria and dengue fever vectors in the laboratory.

    Science.gov (United States)

    Siria, Doreen J; Batista, Elis P A; Opiyo, Mercy A; Melo, Elizangela F; Sumaye, Robert D; Ngowo, Halfan S; Eiras, Alvaro E; Okumu, Fredros O

    2018-04-11

    Controlled blood-feeding is essential for maintaining laboratory colonies of disease-transmitting mosquitoes and investigating pathogen transmission. We evaluated a low-cost artificial feeding (AF) method, as an alternative to direct human feeding (DHF), commonly used in mosquito laboratories. We applied thinly-stretched pieces of polytetrafluoroethylene (PTFE) membranes cut from locally available seal tape (i.e. plumbers tape, commonly used for sealing pipe threads in gasworks or waterworks). Approximately 4 ml of bovine blood was placed on the bottom surfaces of inverted Styrofoam cups and then the PTFE membranes were thinly stretched over the surfaces. The cups were filled with boiled water to keep the blood warm (~37 °C), and held over netting cages containing 3-4 day-old inseminated adults of female Aedes aegypti, Anopheles gambiae (s.s.) or Anopheles arabiensis. Blood-feeding success, fecundity and survival of mosquitoes maintained by this system were compared against DHF. Aedes aegypti achieved 100% feeding success on both AF and DHF, and also similar fecundity rates (13.1 ± 1.7 and 12.8 ± 1.0 eggs/mosquito respectively; P > 0.05). An. arabiensis had slightly lower feeding success on AF (85.83 ± 16.28%) than DHF (98.83 ± 2.29%) though these were not statistically different (P > 0.05), and also comparable fecundity between AF (8.82 ± 7.02) and DHF (8.02 ± 5.81). Similarly, for An. gambiae (s.s.), we observed a marginal difference in feeding success between AF (86.00 ± 10.86%) and DHF (98.92 ± 2.65%), but similar fecundity by either method. Compared to DHF, mosquitoes fed using AF survived a similar number of days [Hazard Ratios (HR) for Ae. aegypti = 0.99 (0.75-1.34), P > 0.05; An. arabiensis = 0.96 (0.75-1.22), P > 0.05; and An. gambiae (s.s.) = 1.03 (0.79-1.35), P > 0.05]. Mosquitoes fed via this simple AF method had similar feeding success, fecundity and longevity. The method could potentially be used for laboratory colonization of mosquitoes

  13. Blood-feeding patterns of native mosquitoes and insights into their potential role as pathogen vectors in the Thames estuary region of the United Kingdom.

    Science.gov (United States)

    Brugman, V A; Hernández-Triana, L M; England, M E; Medlock, J M; Mertens, P P C; Logan, J G; Wilson, A J; Fooks, A R; Johnson, N; Carpenter, S

    2017-03-27

    The range of vertebrate hosts on which species of mosquito blood-feed is an important parameter for identifying potential vectors and in assessing the risk of incursion and establishment of vector-borne pathogens. In the United Kingdom, studies of mosquito host range have collected relatively few specimens and used techniques that could only broadly identify host species. This study conducted intensive collection and analysis of mosquitoes from a grazing marsh environment in southeast England. This site provides extensive wetland habitat for resident and migratory birds and has abundant human nuisance biting mosquitoes. The aim was to identify the blood-feeding patterns of mosquito species present at the site which could contribute to the transmission of pathogens. Twice-weekly collections of mosquitoes were made from Elmley Nature Reserve, Kent, between June and October 2014. Mosquitoes were collected using resting boxes, by aspiration from man-made structures and using a Mosquito Magnet Pro baited with 1-octen-3-ol. Blood-fed specimens were classified according to the degree of blood meal digestion using the Sella scale and vertebrate origin determined using sequencing of a fragment of the mitochondrial cytochrome C oxidase subunit I gene. Mosquitoes that were morphologically cryptic were identified to species level using multiplex PCR and sequencing methods. A total of 20,666 mosquitoes of 11 species were collected, and 2,159 (10.4%) were blood-fed (Sella scale II-VI); of these 1,341 blood-fed specimens were selected for blood meal analysis. Vertebrate origin was successfully identified in 964 specimens (72%). Collections of blood-fed individuals were dominated by Anopheles maculipennis complex (73.5%), Culiseta annulata (21.2%) and Culex pipiens form pipiens (10.4%). Nineteen vertebrate hosts comprising five mammals and 14 birds were identified as hosts for mosquitoes, including two migratory bird species. Feeding on birds by Culex modestus and Anopheles

  14. Cerebral palsy in adult patients: constraint-induced movement therapy is effective to reverse the nonuse of the affected upper limb

    Directory of Open Access Journals (Sweden)

    Ana Cecília P. Oliveira

    2016-01-01

    Full Text Available ABSTRACT Objective To determine if the original protocol of Constraint-Induced Movement Therapy (CIMT, is adequate to reverse the nonuse of the affected upper limb (AUL in patients with Cerebral Palsy (CP in adulthood. Method The study included 10 patients diagnosed with CP hemiparesis had attended the adult protocol CIMT, from January/August 2009/2014. Results Average age 24.6 (SD 9.44; MAL average pretreatment How Often (HO = 0.72 and How Well (HW = 0.68 and post-treatment HO = 3.77 and HW = 3.60 (p ≤ 0.001 and pretreatment WMFT average = 21.03 and post-treatment average = 18.91 (p = 0.350. Conclusion The constraint-induced movement therapy is effective to reverse the nonuse learn of the AUL in adult patients with CP.

  15. Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Tang, Bo; Zheng, Peishi; Zhang, Yang

    2012-11-01

    Endocrine therapy is an important therapeutic approach for the treatment of oestrogen receptor (ER)-positive breast cancer. However, a number of these endocrine therapies can fail when the tumour loses its ER expression during treatment. To date, few studies have explored the potential clinical significance of traditional Chinese medicine in inducing the reversal of resistance to endocrine therapy in breast cancers. We used the ERα-negative MCF7 breast cancer cell line to create a tamoxifen (TAM)-resistant cell line, MCF7/TAM cells. After treating MCF7/TAM cells with ELE to induce the re-expression of ERα, we investigated the role and molecular mechanisms by which elemene (ELE) promotes the reversal of resistance to endocrine therapy. We discovered that treatment with 10 μg/ml ELE restored the sensitivity of MCF7/TAM cells to TAM. RT-PCR analysis revealed that ELE treatment upregulated ERα mRNA levels in MCF7/TAM cells, and immunohistochemistry confirmed the upregulation of ERα expression. Western blot analysis revealed that ELE treatment decreased the protein expression levels of Ras, MEK1/2 and p-ERK1/2 in MCF7/TAM cells. The loss of ERα expression was the primary reason for TAM resistance in MCF7 cells. The ELE-induced reversal of TAM resistance was mediated by the upregulation of ERα mRNA and the re-expression of ERα through the MAPK pathway.

  16. The distribution and function of serotonin in the large milkweed bug, Oncopeltus fasciatus. a comparative study with the blood-feeding bug, Rhodnius prolixus.

    Science.gov (United States)

    Miggiani, L; Orchard, I; TeBrugge, V

    1999-11-01

    The blood-feeding hemipteran, Rhodnius prolixus, ingests a large blood meal at the end of each larval stage. To accommodate and process this meal, its cuticle undergoes plasticisation, and its gut and Malpighian tubules respectively absorb and secrete a large volume of water and salts for rapid diuresis. Serotonin has been found to be integral to the feeding process in this animal, along with a diuretic peptide(s). The large milkweed bug, Oncopeltus fasciatus, tends to feed in a more continuous and abstemious manner, and therefore may have different physiological requirements than the blood feeder. Unlike R. prolixus, O. fasciatus is lacking serotonin-like immunoreactive dorsal unpaired median neurons in the mesothoracic ganglionic mass, and lacks serotonin-like immunoreactive neurohaemal areas and processes on the abdominal nerves, integument, salivary glands, and anterior junction of the foregut and crop. The salivary glands and crop do, however, respond to serotonin with increased levels of cAMP, while the integument and Malpighian tubules do not. In addition, O. fasciatus Malpighian tubules respond to both O. fasciatus and R. prolixus partially purified CNS extracts, which are likely to contain any native diuretic peptides. Thus, while serotonin and diuretic peptides may be involved in tubule control in R. prolixus, the latter may be of greater importance in O. fasciatus.

  17. Glytube: a conical tube and parafilm M-based method as a simplified device to artificially blood-feed the dengue vector mosquito, Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    André Luis Costa-da-Silva

    Full Text Available Aedes aegypti, the main vector of dengue virus, requires a blood meal to produce eggs. Although live animals are still the main blood source for laboratory colonies, many artificial feeders are available. These feeders are also the best method for experimental oral infection of Ae. aegypti with Dengue viruses. However, most of them are expensive or laborious to construct. Based on principle of Rutledge-type feeder, a conventional conical tube, glycerol and Parafilm-M were used to develop a simple in-house feeder device. The blood feeding efficiency of this apparatus was compared to a live blood source, mice, and no significant differences (p = 0.1189 were observed between artificial-fed (51.3% of engorgement and mice-fed groups (40.6%. Thus, an easy to assemble and cost-effective artificial feeder, designated "Glytube" was developed in this report. This simple and efficient feeding device can be built with common laboratory materials for research on Ae. aegypti.

  18. The effects of forced-egg retention on the blood-feeding behavior and reproductive potential of Culex pipiens (Diptera: Culicidae).

    Science.gov (United States)

    Johnson, Brian J; Fonseca, Dina M

    2014-07-01

    High rates of West Nile virus (WNV) transmission to humans are associated with exceptionally hot and dry summers. This is paradoxical since the eggs of Culex vectors of WNV depend on the persistence of containers with water, which decline during droughts. We examined the effects of forced-egg retention on the reproductive success of female Culex pipiens as well as behavioral responses, such as likelihood of secondary blood meals. As controls we examined the effects of female age and delayed mating. We found that early mating is essential to achieve reproductive success and, consistent with an "all-or-none" ovipositing strategy, C. pipiens females are able to retain considerable reproductive potential while searching for oviposition sites. Specifically, although forced-egg retention resulted in significant decreases in fitness, the decline was moderate for 5 weeks and most can be accounted for by increases in female age. Consequently, no females took blood more than once per gonotrophic cycle, which eliminates the possibility that heightened vectorial capacity due to multiple blood-feedings increases WNV transmission during periods of drought. Instead, our findings suggest that during droughts populations of C. pipiens have time to locate the remaining water holes, which are associated with human populations and WNV-competent bird species. Copyright © 2014. Published by Elsevier Ltd.

  19. Blood feeding patterns of Nyssomyia intermedia and Nyssomyia neivai (Diptera, Psychodidae in a cutaneous leishmaniasis endemic area of the Ribeira Valley, State of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Maria Marassa

    2013-09-01

    Full Text Available Introduction The aim of this study was to identify the blood feeding sources of Nyssomyia intermedia (Ny. intermedia and Nyssomyia neivai (Ny. neivai, which are Leishmania vectors and the predominant sandfly species in the Ribeira Valley, State of São Paulo, Brazil, an endemic area for cutaneous leishmaniasis. Methods Specimens were captured monthly between February 2001 and December 2003 on a smallholding and a small farm situated in the Serra district in the Iporanga municipality. The blood meals of 988 engorged females were tested using the avidin-biotin immunoenzymatic enzyme-linked immunosorbent assay (ELISA. Seven blood meal sources were investigated: human, dog, chicken, bovine, pig, horse and rat. Results The results showed that among the females that fed on one or more blood sources, the respective percentages for Ny. intermedia and Ny. neivai, respectively, were as follows: human (23% and 36.8%, pig (47.4% and 26.4%, chicken (25.7% and 36.8% and dog (3.9% and 0%, and the differences in the blood sources between the two species were statistically significant (p = 0.043. Conclusions Both species had predominant reactivity for one or two blood sources, and few showed reactivity indicating three or four sources. Many different combinations were observed among the females that showed reactivity for more than one source, which indicated their opportunistic habits and eclecticism regarding anthropic environmental conditions.

  20. Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening

    International Nuclear Information System (INIS)

    Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C; Konofagou, Elisa E

    2015-01-01

    Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r 2   =  0.77); (2) the permeability of the opened BBB (r 2   =  0.82); (3) the likelihood of safe opening (P  <  0.05, safe opening compared to cases of damage; P  <  0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r 2   =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response

  1. Ethaselen: a novel organoselenium anticancer agent targeting thioredoxin reductase 1 reverses cisplatin resistance in drug-resistant K562 cells by inducing apoptosis.

    Science.gov (United States)

    Ye, Suo-Fu; Yang, Yong; Wu, Lin; Ma, Wei-Wei; Zeng, Hui-Hui

    2017-05-01

    It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase (TrxR) activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin (CDDP) cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and combination index (CI), showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species (ROS) generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores (PTPs). In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB (NF-κB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.

  2. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  3. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    Wu, C-W.; Biggar, K.K.; Storey, K.B.

    2013-01-01

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  4. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Science.gov (United States)

    Wu, C-W.; Biggar, K.K.; Storey, K.B.

    2013-01-01

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans. PMID:23314346

  5. CFD simulation of reverse water-hammer induced by collapse of draft-tube cavity in a model pump-turbine during runaway process

    Science.gov (United States)

    Zhang, Xiaoxi; Cheng, Yongguang; Xia, Linsheng; Yang, Jiandong

    2016-11-01

    This paper reports the preliminary progress in the CFD simulation of the reverse water-hammer induced by the collapse of a draft-tube cavity in a model pump-turbine during the runaway process. Firstly, the Fluent customized 1D-3D coupling model for hydraulic transients and the Schnerr & Sauer cavitation model for cavity development are introduced. Then, the methods are validated by simulating the benchmark reverse water-hammer in a long pipe caused by a valve instant closure. The simulated head history at the valve agrees well with the measured data in literature. After that, the more complicated reverse water-hammer in the draft-tube of a runaway model pump-turbine, which is installed in a model pumped-storage power plant, is simulated. The dynamic processes of a vapor cavity, from generation, expansion, shrink to collapse, are shown. After the cavity collapsed, a sudden increase of pressure can be evidently observed. The process is featured by a locally expending and collapsing vapor cavity that is around the runner cone, which is different from the conventional recognition of violent water- column separation. This work reveals the possibility for simulating the reverse water-hammer phenomenon in turbines by 3D CFD.

  6. The reversible increase in tight junction permeability induced by capsaicin is mediated via cofilin-actin cytoskeletal dynamics and decreased level of occludin.

    Directory of Open Access Journals (Sweden)

    Tomoko Shiobara

    Full Text Available Previous results demonstrated that capsaicin induces the reversible tight junctions (TJ opening via cofilin activation. The present study investigated the mechanisms underlying the reversible TJ opening and compared the effect to the irreversible opening induced by actin inhibitors. Capsaicin treatment induced the F-actin alteration unique to capsaicin compared to actin-interacting agents such as latrunculin A, which opens TJ irreversibly. Along with TJ opening, capsaicin decreased the level of F-actin at bicellular junctions but increased it at tricellular junctions accompanied with its concentration on the apical side of the lateral membrane. No change in TJ protein localization was observed upon exposure to capsaicin, but the amount of occludin was decreased significantly. In addition, cosedimentation analyses suggested a decrease in the interactions forming TJ, thereby weakening TJ tightness. Introduction of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechanism, and suggest that it is a new type of paracellular permeability enhancer.

  7. Tacrolimus Reverses UVB Irradiation-Induced Epidermal Langerhans Cell Reduction by Inhibiting TNF-α Secretion in Keratinocytes via Regulation of NF-κB/p65

    Directory of Open Access Journals (Sweden)

    JiaLi Xu

    2018-02-01

    Full Text Available Background: Topical calcineurin inhibitors including tacrolimus and pimecrolimus are used in the treatment of many inflammatory skin diseases mainly via blocking T-cell proliferation. Our previous studies found that pimecrolimus 1% cream could reverse high-dose ultraviolet B (UVB irradiation-induced epidermal Langerhans cell (LC reduction via inhibition of LC migration. We conducted this study to investigate the effects of topical tacrolimus 0.03% ointment on high-dose UVB-irradiated human epidermal LCs.Methods: Twenty fresh human foreskin tissues were randomly divided into four groups as follows: Control, Tacrolimus (0.03%, UVB (180 mJ/cm2, and UVB (180 mJ/cm2 + Tacrolimus (0.03%. Four time points were set as follows: 0, 18, 24, and 48 h. We collected culture medium and tissues at each time point. The percentage of CD1a+ cells in the medium was detected by means of flow cytometry. Each tissue was prepared for immunohistochemistry, real-time quantitative PCR, and western blot. HaCaT cells were cultured and divided into four groups: Control, Tacrolimus (1 μg/ml, UVB (30 mJ/cm2, and UVB (30 mJ/cm2 + Tacrolimus (1 μg/ml. The cells were incubated for 24 h and prepared for real-time quantitative PCR and western blot.Results: Topical tacrolimus significantly reversed high-dose UVB irradiation-induced epidermal LC reduction and CD1a+ cell increment in culture medium. Tacrolimus significantly inhibited UVB irradiation-induced tumor necrosis factor-α (TNF-α and nuclear factor kappa B (NF-κB/p65 mRNA and protein expression in HaCaT cells. Tacrolimus also significantly inhibited high-dose UVB irradiation-induced TNF-α expression in cultured tissues. Finally, TNF-α antagonist (recombinant human TNF-α receptor II: IgG Fc fusion protein could significantly reverse UVB irradiation-induced epidermal LC reduction.Conclusion: Topical tacrolimus 0.03% could reverse UVB irradiation-induced epidermal LC reduction by inhibiting TNF-α secretion in

  8. A temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in a pediatric patient.

    Science.gov (United States)

    Iwasaki, Hajime; Takahoko, Kenichi; Otomo, Shigeaki; Sasakawa, Tomoki; Kunisawa, Takayuki; Iwasaki, Hiroshi

    2014-04-01

    We report a temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in our dose-finding study in pediatric patients. A 19-month-old female infant (9.6 kg, 80 cm) was scheduled for elective cheiloplasty surgery. Anesthesia was induced with nitrous oxide 50% and sevoflurane 5% and maintained with air, oxygen, sevoflurane 3%, and fentanyl (total, 3 μg/kg). Neuromuscular monitoring was performed at the adductor pollicis muscle after induction of anesthesia but before the administration of rocuronium. Total dose of rocuronium during the surgery was 0.9 mg/kg. Neuromuscular block was reversed with 0.5 mg/kg sugammadex when one response was observed with post-tetanic count stimulation. Twitch responses after sugammadex administration showed a temporary decrease after its initial recovery. Maximum decreases in twitch responses were observed 17 min after initial dose of sugammadex. Twitch responses recovered to their control values after additional doses of 3.5 mg/kg sugammadex (4 mg/kg in total). Time from sugammadex administration to maximum decreases in twitch responses is earlier than has been reported in adults (20-70 min). It is demonstrated that following neuromuscular block reversal with insufficient dose of sugammadex, there is a possibility of the recurrence of residual paralysis within less than 20 min in pediatric patients.

  9. β-Carboline harmine reverses the effects induced by stress on behaviour and citrate synthase activity in the rat prefrontal cortex.

    Science.gov (United States)

    Abelaira, Helena Mendes; Réus, Gislaine Zilli; Scaini, Giselli; Streck, Emilio Luiz; Crippa, José Alexandre; Quevedo, João

    2013-12-01

    The present study was aimed at evaluating the effects of the administration of β-carboline harmine on behaviour and citrate synthase activity in the brain of rats exposed to chronic mild stress (CMS) procedure. To this aim, after 40 days of exposure to CMS procedure, rats were treated with harmine (15 mg/kg/day) for 7 days, then memory, anhedonia and citrate synthase activity were assessed. Result Our findings demonstrated that stressed rats treated with saline increased the sucrose intake, and the stressed rats treated with harmine reversed this effect. Neither stress nor harmine treatment altered memory performance in rats. In addition, chronic stressful situations induced increase in citrate synthase activity in the prefrontal cortex, but not in the hippocampus and striatum. Treatment with harmine reversed the increase in citrate synthase activity in the prefrontal cortex. These findings support the hypothesis that harmine could be involved in controlling the energy metabolism.

  10. Stress-induced visceral hypersensitivity in maternally separated rats can be reversed by peripherally restricted histamine-1-receptor antagonists

    NARCIS (Netherlands)

    Stanisor, Oana I.; van Diest, Sophie A.; Yu, Zhumei; Welting, Olaf; Bekkali, Noor; Shi, Jing; de Jonge, Wouter J.; Boeckxstaens, Guy E.; van den Wijngaard, Rene M.

    2013-01-01

    The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse

  11. An In Vitro Blood-Feeding Method Revealed Differential Borrelia turicatae (Spirochaetales: Spirochaetaceae) Gene Expression After Spirochete Acquisition and Colonization in the Soft Tick Ornithodoros turicata (Acari: Argasidae).

    Science.gov (United States)

    Neelakanta, Girish; Sultana, Hameeda; Sonenshine, Daniel E; Marconi, Richard T

    2017-03-01

    In the Midwestern, Southwestern, and Southern part of the United States, the soft tick Ornithodoros turicata transmits the spirochete Borrelia turicatae, the causative agent of relapsing fever in humans. In this study, we report a simplified and an efficient method of in vitro feeding to evaluate O. turicata-B. turicatae interactions. Both nymphal and adult female ticks successfully acquired spirochetes upon in vitro feeding on the B. turicatae-infected blood. We also noted transstadial transmission of spirochetes to adult ticks that were molted from nymphs fed on B. turicatae-infected blood. A differential expression pattern for some of the B. turicatae genes was evident after acquisition and colonization of the vector. The levels of arthropod-associated lipoprotein Alp-mRNA were significantly upregulated and the mRNA levels of factor H binding protein FhbA and immunogenic protein BipA were significantly downregulated in the spirochetes after acquisition into ticks in comparison with spirochetes grown in culture medium. In addition, genes such as bta124 and bta116 were significantly upregulated in spirochetes in unfed ticks in comparison with the levels noted in spirochetes after acquisition. These findings represent an efficient in vitro blood-feeding method to study B. turicatae gene expression after acquisition and colonization in these ticks. In summary, we report that B. turicatae survive and develop in the tick host when acquired by in vitro feeding. We also report that B. turicatae genes are differentially expressed in ticks in comparison with the in vitro-grown cultures, indicating influence of tick environment on spirochete gene expression. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four: A Randomized Controlled Trial.

    Science.gov (United States)

    Asztalos, László; Szabó-Maák, Zoltán; Gajdos, András; Nemes, Réka; Pongrácz, Adrienn; Lengyel, Szabolcs; Fülesdi, Béla; Tassonyi, Edömér

    2017-09-01

    Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.

  13. Molecular characterization and immunolocalization of the olfactory co-recepter Orco from two blood-feeding muscid flies, the stable fly (Stomoxys calcitrans, L.) and the horn fly (Haematobia irritans irritans, L.)

    OpenAIRE

    Olafson, Pia Untalan

    2013-01-01

    Biting flies are economically important, blood-feeding pests of medical and veterinary significance. Chemosensory-based biting fly behaviors, such as host/nutrient source localization and ovipositional site selection, are intriguing targets for the development of supplemental control strategies. In an effort to expand our understanding of biting fly chemosensory pathways, transcripts encoding the highly conserved insect odorant co-receptor (Orco) were isolated from two representative biting f...

  14. Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells.

    Science.gov (United States)

    Liu, Zhiqi; Liu, Jie; Zhao, Li; Geng, Hao; Ma, Jiaxing; Zhang, Zhiqiang; Yu, Dexin; Zhong, Caiyun

    2017-04-01

    Overexposure to benzidine has been manifested as an important cause of bladder cancer. However, the molecular mechanism of benzidine-induced malignancy is still insufficiently interpreted. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in embryonic development as well as initiation and development of epithelium-originated malignant tumors. The role of extracellular regulated protein kinase 5 (ERK5) in benzidine-meditated bladder cancer development has not been explored. In the present study, we explored the role of ERK5/AP-1 pathway in benzidine-induced EMT in human normal urothelial cells and the intervention effect of curcumin on bezidine-induced EMT. We found that benzidine-induced EMT in SV-40 immortalized human urothelial cells (SV-HUC-1) at low concentrations. We detected that ERK5/AP-1 pathway was notably activated. Specific ERK5 inhibitor, XMD8-92 was applied to determine the role of ERK5 in benzidine-induced EMT. Results indicated that XMD8-92 reversed the EMT process. Furthermore, curcumin effectively attenuated benzidine-induced urocystic EMT by suppressing ERK5/AP-1 pathway. In conclusion, the present study revealed the positive role of ERK5/AP-1 in benzidine-provoked urocystic EMT and the curcumin promising use in bladder cancer prevention and intervention via ERK5/AP-1 pathway.

  15. Reversible strain-induced magnetization switching in FeGa nanomagnets: Pathway to a rewritable, non-volatile, non-toggle, extremely low energy straintronic memory.

    Science.gov (United States)

    Ahmad, Hasnain; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    2015-12-14

    We report reversible strain-induced magnetization switching between two stable/metastable states in ~300 nm sized FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. Voltage of one polarity applied across the substrate generates compressive strain in a nanomagnet and switches its magnetization to one state, while voltage of the opposite polarity generates tensile strain and switches the magnetization back to the original state. The two states can encode the two binary bits, and, using the right voltage polarity, one can write either bit deterministically. This portends an ultra-energy-efficient non-volatile "non-toggle" memory.

  16. Early postmenopausal phase is associated with reduced prostacyclin-induced vasodilation that is reversed by exercise training

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Egelund, Jon; Mandrup Jensen, Camilla Maria

    2016-01-01

    to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent......The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We...... examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age...

  17. Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Gwanhee Ehm

    2011-10-01

    Full Text Available Background: Myoclonus and encephalopathy are unusual in patients with Parkinson’s disease (PD.Case report: We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement.Discussion: Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

  18. Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

    Science.gov (United States)

    Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

  19. Reverse Transcriptase-Containing Particles Induced in Rous Sarcoma Virus-Transformed Rat Cells by Arginine Deprivation

    Science.gov (United States)

    Kotler, Moshe; Weinberg, Eynat; Haspel, Osnat; Becker, Yechiel

    1972-01-01

    Incubation of rat cells transformed by Rous sarcoma virus (RSV) in an arginine-deficient medium resulted in accumulation of particles in the culture medium. Such particles did not appear when the transformed rat cells were incubated in a complete medium nor in the medium of primary rat cells which were incubated either in arginine-deficient or complete media. The particles which were released from the arginine-deprived transformed rat cells resemble C-type particles in their properties. These particles band in sucrose gradients at a density of 1.16 g/ml and contain 35S ribonucleic acid (RNA) molecules and a reverse transcriptase activity. Analysis of the cytoplasm of transformed and primary rat cells, deprived and undeprived of arginine, revealed the presence of reverse transcriptase-containing particles which banded in sucrose gradients at a density of 1.14 g/ml. These particles differed from the particles released into the medium by the arginine-deprived RSV-transformed rat cells. The deoxyribonucleic acid (DNA) molecules synthesized in vitro by the reverse transcriptase present in the particles isolated from the medium of arginine-deprived cells hybridized to RSV RNA, whereas the DNA synthesized by the cell-bound enzyme had no homology to RSV RNA. PMID:4116137

  20. Postincubation with aclarubicin reverses topoisomerase II mediated DNA cleavage, strand breaks, and cytotoxicity induced by VP-16

    DEFF Research Database (Denmark)

    Petersen, L N; Jensen, P B; Sørensen, B S

    1994-01-01

    In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed strand break formation was prevented in a small cell lung cancer (SCLC) cell line, when the cells were incubated with aclarubicin prior to treatment with VP-16. In the present work, we studied the effect...... of adding aclarubicin to the cell suspension after VP-16. In a clonogenic assay, we found that the cytotoxicity induced by VP-16 in SCLC cells was inhibited when cells were postincubated with aclarubicin. The addition of aclarubicin at any time in relation to VP-16 was able to stop further cytotoxicity...... induced by the topoisomerase II (topo-II) targeting drug. Aclarubicin was also found to antagonize the cytotoxicity induced by VM-26 (teniposide), and m-AMSA. With the alkaline elution technique we found that postincubating the cells with aclarubicin inhibited VP-16-induced DNA strand break formation...

  1. Estrogen receptor 1 (ESR1; ERα), not ESR2 (ERβ), modulates estrogen-induced sex reversal in the American alligator, a species with temperature-dependent sex determination.

    Science.gov (United States)

    Kohno, Satomi; Bernhard, Melissa C; Katsu, Yoshinao; Zhu, Jianguo; Bryan, Teresa A; Doheny, Brenna M; Iguchi, Taisen; Guillette, Louis J

    2015-05-01

    All crocodilians and many turtles exhibit temperature-dependent sex determination where the temperature of the incubated egg, during a thermo-sensitive period (TSP), determines the sex of the offspring. Estrogens play a critical role in sex determination in crocodilians and turtles, as it likely does in most nonmammalian vertebrates. Indeed, administration of estrogens during the TSP induces male to female sex reversal at a male-producing temperature (MPT). However, it is not clear how estrogens override the influence of temperature during sex determination in these species. Most vertebrates have 2 forms of nuclear estrogen receptor (ESR): ESR1 (ERα) and ESR2 (ERβ). However, there is no direct evidence concerning which ESR is involved in sex determination, because a specific agonist or antagonist for each ESR has not been tested in nonmammalian species. We identified specific pharmaceutical agonists for each ESR using an in vitro transactivation assay employing American alligator ESR1 and ESR2; these were 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and 7-bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY 200070), respectively. Alligator eggs were exposed to PPT or WAY 200070 at a MPT just before the TSP, and their sex was examined at the last stage of embryonic development. Estradiol-17β and PPT, but not WAY 200070, induced sex reversal at a MPT. PPT-exposed embryos exposed to the highest dose (5.0 μg/g egg weight) exhibited enlargement and advanced differentiation of the Müllerian duct. These results indicate that ESR1 is likely the principal ESR involved in sex reversal as well as embryonic Müllerian duct survival and growth in American alligators.

  2. Pressure-induced reversible amorphization and an amorphous-amorphous transition in Ge₂Sb₂Te₅ phase-change memory material.

    Science.gov (United States)

    Sun, Zhimei; Zhou, Jian; Pan, Yuanchun; Song, Zhitang; Mao, Ho-Kwang; Ahuja, Rajeev

    2011-06-28

    Ge(2)Sb(2)Te(5) (GST) is a technologically very important phase-change material that is used in digital versatile disks-random access memory and is currently studied for the use in phase-change random access memory devices. This type of data storage is achieved by the fast reversible phase transition between amorphous and crystalline GST upon heat pulse. Here we report pressure-induced reversible crystalline-amorphous and polymorphic amorphous transitions in NaCl structured GST by ab initio molecular dynamics calculations. We have showed that the onset amorphization of GST starts at approximately 18 GPa and the system become completely random at approximately 22 GPa. This amorphous state has a cubic framework (c-amorphous) of sixfold coordinations. With further increasing pressure, the c-amorphous transforms to a high-density amorphous structure with trigonal framework (t-amorphous) and an average coordination number of eight. The pressure-induced amorphization is investigated to be due to large displacements of Te atoms for which weak Te-Te bonds exist or vacancies are nearby. Upon decompressing to ambient conditions, the original cubic crystalline structure is restored for c-amorphous, whereas t-amorphous transforms to another amorphous phase that is similar to the melt-quenched amorphous GST.

  3. Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.

    Science.gov (United States)

    Zhang, Hao; Zhang, Shao-Bo; Zhang, Qing-Qing; Liu, Meng; He, Xing-Ying; Zou, Zui; Sun, Hai-Jing; You, Zhen-Dong; Shi, Xue-Yin

    2013-07-01

    The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling. © 2013 John Wiley & Sons Ltd.

  4. Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells.

    Science.gov (United States)

    Li, Chun; Guan, Xingang; Xue, Haogang; Wang, Peng; Wang, Manli; Gai, Xiaodong

    2017-07-01

    Multidrug resistance (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene is major obstacles for successful cancer chemotherapy. P-gp could extrude anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. MDR reversal agents for P-gp can restore the sensitivity of MDR cells to such drugs. Saikosaponin D (SSd), one of the major triterpenoid saponins derived from Bupleurum chinense DC (BCDC), has been shown to possess anti-inflammatory, anti-infectious and anti-tumor properties. The aim of the present study was to investigate the reversal effect of SSd on MDR in MCF-7/adriamycin (ADR) human breast cancer cells and investigate the underlying mechanisms of SSd. The results demonstrated that SSd inhibited the proliferation of MCF-7/ADR and MCF-7 cells in a dose-dependent manner. Moreover, SSd increased the cytotoxicity of ADR on MCF-7/ADR cells and the resistance fold of SSd treatment was demonstrated to be significantly higher when compared with that of the group without SSd treatment. Additionally, the effects of the drug combination showed that SSd and ADR combination were synergistic. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that SSd restored Rh123 accumulation and inhibited P-gp-mediated drug efflux. Importantly, we found that SSd could enhance the sensitivity of MCF-7/ADR cells towards ADR by down-regulating MDR1 and P-gp expression. In conclusion, the results of the present study indicated that SSd may represent a potent reversal agent for P-gp-mediated MDR in breast cancer therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. High-throughput investigation of orientations effect on nanoscale magnetization reversal in cobalt ferrite thin films induced by electric field

    Science.gov (United States)

    Dhanapal, Pravarthana; Guo, Shanshan; Wang, Baomin; Yang, Huali; Agarwal, Sandeep; Zhan, Qingfeng; Li, Run-Wei

    2017-10-01

    The magnetoelectric device concept which enables the non-volatile electric field control of magnetism needs to be investigated for the development of practical information storage devices. In this aspect, the emerging field of magneto-ionics based on the modulation of magnetism by field-driven ion migration is promising because it only requires a simple sample structure in the solid state and has good cyclability. However, the degree of ion migration within the magnetic structure is strongly dependent on the crystal orientations. Since the epitaxial films growing on the commercial single crystal substrates have limited orientations, the ability of magnetism modulated by field-driven ion migration cannot be optimized and understood by using these data. In this work, we utilized the high-throughput synthesis approach, namely, combinatorial substrate epitaxy, which utilizes a polycrystalline substrate. This provides a platform to develop and understand the degree of ionic migration in different orientations of the model system CoFe2O4 (CFO) films. The library of electric driven nanoscale magnetization reversal data of CFO with different orientations was obtained by applying the electric field in the same region of known CFO grain orientations. It was determined from the analysis that the [110] crystal direction exhibits the maximum nanoscale magnetization reversal ratio. This is mainly attributed to the ease Co2+ migration in the [110] direction under the electric field assisted by a Fe3+ and oxygen vacancies.

  6. Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

    Science.gov (United States)

    Horiguchi, M; Meltzer, H Y

    2013-06-15

    Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Reverse Osmosis

    Indian Academy of Sciences (India)

    ment of Civil Engineering and is presently the. Chairman of Center for. Sustainable Technologies,. Indian Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis,.

  8. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  9. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

    Directory of Open Access Journals (Sweden)

    Lourdes Sánchez-Sevilla

    2016-10-01

    Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

  10. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration.

    Science.gov (United States)

    Sánchez-Sevilla, Lourdes; Mendieta-Condado, Edgar; Hernández-Muñoz, Rolando

    2016-10-26

    The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar) treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC), and polyamine levels, were determined. Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also "synchronized" by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased retinoid levels induced by α-tocopherol. Therefore interactions

  11. Nitrite exerts antioxidant effects, inhibits the mTOR pathway and reverses hypertension-induced cardiac hypertrophy.

    Science.gov (United States)

    Guimaraes, Danielle A; Dos Passos, Madla A; Rizzi, Elen; Pinheiro, Lucas C; Amaral, Jefferson H; Gerlach, Raquel F; Castro, Michele M; Tanus-Santos, Jose E

    2018-03-09

    Cardiac hypertrophy is a common consequence of chronic hypertension and leads to heart failure and premature death. The anion nitrite is now considered as a bioactive molecule able to exert beneficial cardiovascular effects. Previous results showed that nitrite attenuates hypertension-induced increases in reactive oxygen species (ROS) production in the vasculature. Whether antioxidant effects induced by nitrite block critical signaling pathways involved in cardiac hypertrophy induced by hypertension has not been determined yet. The Akt/mTOR signaling pathway is responsible to activate protein synthesis during cardiac remodeling and is activated by increased ROS production, which is commonly found in hypertension. Here, we investigated the effects of nitrite treatment on cardiac remodeling and activation of this hypertrophic signaling pathway in 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral nitrite at 1 or 15mg/kg for four weeks. Nitrite treatment (15mg/kg) reduced systolic blood pressure and decreased ROS production in the heart tissue from hypertensive rats. This nitrite dose also blunted hypertension-induced activation of mTOR pathway and cardiac hypertrophy. While the lower nitrite dose (1mg/kg) did not affect blood pressure, it exerted antioxidant effects and tended to attenuate mTOR pathway activation and cardiac hypertrophy induced by hypertension. Our findings provide strong evidence that nitrite treatment decreases cardiac remodeling induced by hypertension as a result of its antioxidants effects and downregulation of mTOR signaling pathway. This study may help to establish nitrite as an effective therapy in hypertension-induced cardiac hypertrophic remodeling. Copyright © 2018. Published by Elsevier Inc.

  12. p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells

    Directory of Open Access Journals (Sweden)

    Giacinti Cristina

    2005-12-01

    Full Text Available Abstract Background p21WAF1, implicated in the cell cycle control of both normal and malignant cells, can be induced by p53-dependent and independent mechanisms. In some cells, MEKs/ERKs regulate p21WAF1 transcriptionally, while in others they also affect the post-transcriptional processes. In myogenic differentiation, p21WAF1 expression is also controlled by the myogenic transcription factor MyoD. We have previously demonstrated that the embryonal rhabdomyosarcoma cell line undergoes growth arrest and myogenic differentiation following treatments with TPA and the MEK inhibitor U0126, which respectively activate and inhibit the ERK pathway. In this paper we attempt to clarify the mechanism of ERK-mediated and ERK-independent growth arrest and myogenic differentiation of embryonal and alveolar rhabdomyosarcoma cell lines, particularly as regards the expression of the cell cycle inhibitor p21WAF1. Results p21WAF1 expression and growth arrest are induced in both embryonal (RD and alveolar (RH30 rhabdomyosarcoma cell lines following TPA or MEK/ERK inhibitor (U0126 treatments, whereas myogenic differentiation is induced in RD cells alone. Furthermore, the TPA-mediated post-transcriptional mechanism of p21WAF1-enhanced expression in RD cells is due to activation of the MEK/ERK pathway, as shown by transfections with constitutively active MEK1 or MEK2, which induces p21WAF1 expression, and with ERK1 and ERK2 siRNA, which prevents p21WAF1 expression. By contrast, U0126-mediated p21WAF1 expression is controlled transcriptionally by the p38 pathway. Similarly, myogenin and MyoD expression is induced both by U0126 and TPA and is prevented by p38 inhibition. Although MyoD and myogenin depletion by siRNA prevents U0126-mediated p21WAF1 expression, the over-expression of these two transcription factors is insufficient to induce p21WAF1. These data suggest that the transcriptional mechanism of p21WAF1 expression in RD cells is rescued when MEK/ERK inhibition

  13. Pathways of Acetyl-CoA Metabolism Involved in the Reversal of Palmitate-Induced Glucose Production by Metformin and Salicylate.

    Science.gov (United States)

    Hayward, B; Molero, J C; Windmill, K; Sanigorski, A; Weir, J; McRae, N L; Aston-Mourney, K; Osborne, B; Liao, B; Walder, K R; Meikle, P J; Konstantopoulos, N; Schmitz-Peiffer, C

    2016-09-29

    The pathways through which fatty acids induce insulin resistance have been the subject of much research. We hypothesise that by focussing on the reversal of insulin resistance, novel insights can be made regarding the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered during the prevention of palmitate-induced glucose production in hepatocytes using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075 mM, 48 h) with or without metformin (0.25 mM) and sodium salicylate (2 mM) in the final 24 h of palmitate treatment, and effects on glucose production were determined. RNA microarray measurements followed by gene set enrichment analysis were performed to investigate pathway regulation. Lipidomic analysis and measurement of secreted bile acids and cholesterol were also performed. Reversal of palmitate-induced glucose production by metformin and sodium salicylate was characterised by co-ordinated down-regulated expression of pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. All 20 enzymes that regulate the conversion of acetyl-CoA to cholesterol were reduced following metformin and sodium salicylate. Selected findings were confirmed using primary mouse hepatocytes. Although total intracellular levels of diacylglycerol, triacylglycerol and cholesterol esters increased with palmitate, these were not, however, further altered by metformin and sodium salicylate. 6 individual diacylglycerol, triacylglycerol and cholesterol ester species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. These results implicate acetyl-CoA metabolism and C18 lipid species as modulators of hepatic glucose production that could be targeted to improve glucose homeostasis. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Allami, Nika; Javadi-Paydar, Mehrak; Rayatnia, Farhoud; Sehhat, Kourosh; Rahimian, Reza; Norouzi, Abbas; Dehpour, Ahmad Reza

    2011-01-10

    Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), which is widely used in treatment of type 2 diabetes, has shown some therapeutic effect in Alzheimer's disease. In this study, effects of acute pioglitazone on acquisition, consolidation and retrieval of memory, and also the involvement of nitric oxide (NO) in the effects of pioglitazone on spatial recognition memory has been investigated in a two-trial recognition Y-maze test and passive avoidance in mice. Memory impairment was induced by scopolamine (1mg/kg, i.p.). Pioglitazone (10 and 20mg/kg, p.o.) was administrated prior to either acquisition, consolidation or retention trials, while L-NAME (N-nitro-l-arginine methyl ester), a non-specific NO synthase inhibitor, was administered (10mg/kg, i.p.) 30min before each trial. 1) pioglitazone improved the acquisition of recognition spatial memory-impaired by scopolamine; L-NAME dramatically reversed improving effects of pioglitazone on memory acquisition; 2) pioglitazone did not change the consolidation of spatial memory, impaired by scopolamine; 3) pioglitazone improved the retrieval of spatial memory and L-NAME did not alter the beneficial effect of pioglitazone; 4) pioglitazone did not affect scopolamine-induced cognitive impairments in the passive avoidance test. The present study demonstrates the beneficial effect of acute pioglitazone administration on acquisition and retrieval of scopolamine-induced cognitive deficits. This effect was reversed only in acquisition phase by nitric oxide synthase inhibitor, L-NAME, therefore, it could be concluded that NO might be involved in the pioglitazone beneficial effect of spatial memory acquisition. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Cocaine reverses the naltrexone-induced reduction in operant ethanol self-administration: the effects on immediate-early gene expression in the rat prefrontal cortex.

    Science.gov (United States)

    Echeverry-Alzate, Víctor; Tuda-Arízcun, María; Bühler, Kora-Mareen; Santos, Ángel; Giné, Elena; Olmos, Pedro; Gorriti, Miguel Ángel; Huertas, Evelio; Rodríguez de Fonseca, Fernando; López-Moreno, Jose Antonio

    2012-11-01

    Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effectiveness of naltrexone co-administered with cocaine and the association of these substances with immediate-early gene expression in the rat prefrontal cortex. We used chronic operant ethanol self-administration and oral treatments prescribed for alcoholism and available in pharmacies to maximise the predictive validity in humans. We performed real-time PCR analysis to determine gene expression levels in the prefrontal cortex. Only the highest dose of naltrexone (1, 3, and 10 mg/kg, p.o.) reduced the response to ethanol. Cocaine increased ethanol self-administration in a dose-dependent manner (2.5, 10, 20 mg/kg, i.p.) and reversed the naltrexone-induced reduction. Naltrexone failed to prevent the cocaine-induced increase in locomotor activity observed in these animals. Chronic self-administration of ethanol reduced the expression of the C-fos gene 4- to 12-fold and increased expression of the COX-2 (up to 4-fold) and Homer1a genes in the rat prefrontal cortex. Chronic ethanol self-administration is prevented by naltrexone, but cocaine fully reverses this effect. This result suggests that cocaine may overcome naltrexone's effectiveness as a treatment for alcoholism. The ethanol-induced reduction in C-fos gene expression in the prefrontal cortex reveals an abnormal activity of these neurons, which may be relevant in the compulsive consumption of ethanol, the control of reward-related areas and the behavioural phenotype of ethanol addiction. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    Science.gov (United States)

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  17. Reversible and irreversible temperature-induced changes in exchange-biased planar Hall effect bridge (PHEB) magnetic field sensors

    DEFF Research Database (Denmark)

    Rizzi, G.; Lundtoft, N.C.; Østerberg, F.W.

    2012-01-01

    We investigate the changes of planar Hall effect bridge magnetic field sensors upon exposure to temperatures between 25° C and 90°C. From analyses of the sensor response vs. magnetic fields we extract the exchange bias field Hex, the uniaxial anisotropy field HK and the anisotropic...... magnetoresistance (AMR) of the exchange biased thin film at a given temperature and by comparing measurements carried out at elevated temperatures T with measurements carried out at 25° C after exposure to T, we can separate the reversible from the irreversible changes of the sensor. The results are not only...... relevant for sensor applications but also demonstrate the method as a useful tool for characterizing exchange-biased thin films....

  18. Parity-even and time-reversal-odd neutron optical potential in spinning matter induced by gravitational torsion

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, A.N., E-mail: ivanov@kph.tuwien.ac.at [Atominstitut, Technische Universität Wien, Stadionallee 2, A-1020 Wien (Austria); Snow, W.M., E-mail: wsnow@indiana.edu [Indiana University, Bloomington, IN 47408 (United States); Center for Exploration of Energy and Matter, Indiana University, Bloomington, IN 47408 (United States)

    2017-01-10

    Recent theoretical work has shown that spin 1/2 particles moving through unpolarized matter which sources torsion fields experience a new type of parity-even and time-reversal-odd optical potential if the matter is spinning in the lab frame. This new type of optical potential can be sought experimentally using the helicity dependence of the total cross sections for longitudinally polarized neutrons moving through a rotating cylindrical target. In combination with recent experimental constraints on short-range P-odd, T-even torsion interactions derived from polarized neutron spin rotation in matter one can derive separate constraints on the time components of scalar and pseudoscalar torsion fields in matter. We estimate the sensitivity achievable in such an experiment and briefly outline some of the potential sources of systematic error to be considered in any future experimental search for this effect.

  19. Cytosolic RNA:DNA Duplexes Generated by Endogenous Reverse Transcriptase Activity as Autonomous Inducers of Skin Inflammation in Psoriasis.

    Science.gov (United States)

    Molès, Jean-Pierre; Griez, Anthony; Guilhou, Jean-Jacques; Girard, Céline; Nagot, Nicolas; Van de Perre, Philippe; Dujols, Pierre

    2017-01-01

    Psoriasis is a chronic skin disease of unknown ætiology. Recent studies suggested that a large amount of cytosolic DNA (cyDNA) in keratinocytes is breaking keratinocytes DNA tolerance and promotes self-sustained inflammation in the psoriatic lesion. We investigated the origin of this cyDNA. We show that, amongst all the possible DNA structures, the cyDNA could be present as RNA:DNA duplexes in keratinocytes. We further show that endogenous reverse transcriptase activities generate such duplexes and consequently activate the production of Th1-inflammatory cytokines. These observations open a new research avenue related to endogenous retroelements for the aetiology of psoriasis and probably of other human chronic inflammatory diseases.

  20. A Reversible, Charge-Induced Intramolecular C4a-S-Cysteinyl-Flavin in Choline Oxidase Variant S101C.

    Science.gov (United States)

    Su, Dan; Yuan, Hongling; Gadda, Giovanni

    2017-12-26

    Choline oxidase serves as a paradigm for alcohol oxidation catalyzed by flavin-dependent enzymes. In its active site, S101 is 4 Å from the flavin C4a atom on an extended loop. Enzyme variants substituted at S101 were generated in a previous study and investigated mechanistically [Yuan, H., and Gadda, G. (2011) Biochemistry 50, 770-779]. In this study, the typical ultraviolet-visible (UV-vis) absorption spectrum of oxidized flavin was observed for the S101C enzyme in HEPES, TES, or sodium phosphate, whereas an absorption spectrum suggesting the presence of a C4a-flavin adduct with cysteine was obtained in Tris-HCl at pH 8.0. pH titrations of the UV-vis absorption spectrum of the wild-type, S101A, S101C, and H99N enzymes in the presence and absence of Tris allowed for the determination of two pK a values that define a pH range in which the C4a-S-cysteinyl flavin is stabilized. Inhibition studies and stopped-flow kinetics demonstrated that binding of protonated Tris in the active site of the S101C enzyme is required to form the C4a-S-cysteinyl flavin. Deuterium kinetic isotope effects and proton inventories of the S101C enzyme mixed in a stopped-flow spectrophotometer with Tris established a mechanism for the reversible formation of the C4a-S-cysteinyl flavin. This study provides a detailed mechanistic analysis of the reversible formation of a bicovalent C4a-S-cysteinyl-8α-N 3 -histidyl flavin in choline oxidase, identifying an optimal pH range and a mechanistic rationale for the stabilization of de novo C4a-S-cysteinyl-flavins. Moreover, it presents an example of an intramolecular reaction of an enzyme-bound flavin without a substrate.

  1. Cananga odorata essential oil reverses the anxiety induced by 1-(3-chlorophenyl) piperazine through regulating the MAPK pathway and serotonin system in mice.

    Science.gov (United States)

    Zhang, Nan; Zhang, Lei; Feng, Linyin; Yao, Lei

    2018-03-12

    Cananga odorata essential oil, known as ylang-ylang essential oil (YYO), was commonly used in the aromatherapy for relaxation and mood adjusting use. In our previous study, YYO played anxiolytic effects on the mice in several behavioral tests that based on the instinctive responses to novel environments. To investigate the effects and mechanisms of YYO reversing the anxiety induced by 5-HT2C receptor agonist 1-(3-chlorophenyl) piperazine (m-CPP). m-CPP was administrated to the male ICR mice to develop an anxiety model. The anxiolytic effect of YYO (0.1%, 1% and 10%, v/v) was evaluated in the elevated plus maze (EPM) test after odor exposure. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) and the expression of c-Fos in the prefrontal cortex (PFC) and hippocampus after the EPM test. Serotonin and its metabolite change in the brain were detected by liquid chromatogram with an electrochemical detector. The effect of YYO on the plasma corticosterone level was evaluated using enzyme-linked immunosorbent assay (ELISA) after the odor exposure. The behavior analysis showed that m-CPP (2 mg/kg and 4 mg/kg) could induce anxiety behaviors in the mice while diazepam (2 mg/kg) reversed the anxiety behavior induced by m-CPP. YYO dose-dependently increased the time and number of entries in the open arms (p < 0.05) compared to the Tween 80 group. YYO reduced the phosphorylation levels of ERK1/2 (p < 0.05) in both PFC and hippocampus. Down-regulations of phosphor-CREB (p < 0.05) and c-Fos (p < 0.05) were only observed in the hippocampus. YYO also affected the brain serotonin metabolism and reduced the blood plasma corticosterone level of the m-CPP treated mice. YYO odor exposure could reverse the anxiety behaviors generated by m-CPP. The anxiolytic effect of YYO was associated with the ERK1/2/CREB pathway in the hippocampus and relevant to the

  2. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.

    Science.gov (United States)

    Begg, Denovan P; Mul, Joram D; Liu, Min; Reedy, Brianne M; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

    2013-03-01

    Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

  3. Reversal of second-hand cigarette smoke-induced impairment of corneal wound healing by thymosin beta4 combined with anti-inflammatory agents.

    Science.gov (United States)

    Yuan, Hongwei; Ma, Chongze; Moinet, Lisa; Sato, Noboru; Martins-Green, Manuela

    2010-05-01

    Abnormalities in corneal reepithelialization caused by second-hand cigarette smoke (CS) are less known than the effects of CS on other tissues. The effects of CS on corneal epithelial cell migration and associated signaling mechanisms were examined, to determine the mechanisms by which CS delays corneal wound healing. Corneal epithelial cells in two-dimensional or organ culture were exposed to sidestream whole (SSW) smoke, a major component of second-hand CS. Thymosin beta 4 (Tbeta4), a molecule thought to promote wound healing in the cornea, was tested to determine whether it can reverse the adverse effects of SSW smoke on corneal healing. Cell migration, actin reorganization, and phosphorylation of focal adhesion kinase (FAK) and paxillin were all inhibited by exposure to SSW smoke, and the distribution of phospho-src in the cells was disrupted. Activation of RhoA, an important regulator of the cytoskeleton during cell migration, was also inhibited. Tbeta4 stimulated corneal epithelial cell migration in the presence of SSW smoke in culture and in vivo, and it partially reversed the inhibition of corneal healing by SSW smoke. However, Tbeta4 plus dexamethasone, an inhibitor of inflammation, together, reversed the effects of SSW smoke on corneal healing. These findings suggest that SSW smoke exerts its effects on cell migration during corneal epithelial healing through inhibition of actin reorganization, activation of focal adhesion molecules, formation of the focal adhesion complex, and activation of Rho-GTPases. Furthermore, they strongly suggest that corneal injury induced by toxicants can be treated using anti-inflammatory agents coupled with Tbeta4.

  4. Facilitating influence of stress on the consolidation of fear memory induced by a weak training: reversal by midazolam pretreatment.

    Science.gov (United States)

    Maldonado, Noelia Martina; Martijena, Irene Delia; Molina, Víctor Alejandro

    2011-11-20

    It is well known that an emotionally arousing experience usually results in a robust and persistent memory trace. The present study explored the potential mechanisms involved in the influence of stress on the consolidation of a contextual fear memory in animals subjected to a weak fear training protocol, and whether pretreatment with intra-basolateral amygdala or systemic administration of midazolam (MDZ) prevents the potential stress-induced influence on fear memory formation. A previous restraint session facilitated fear retention, this effect was not due to a sensitized effect of restraint on the footshock experience. MDZ, both systemically or intra-basolateral amygdala infusion prior to the restraint, attenuated the stress-induced promoting influence on fear memory formation. In addition, stress exposure activated the ERK1/2 pathway in basolateral amygdala (BLA) after the weak training procedure but not after the immediate footshock protocol. Similar to our behavioral findings, MDZ attenuated stress-induced elevation of phospho-ERK2 (p-ERK2) in BLA following the acquisition session. Given that the activation of ERK1/2 pathway is essential for associative learning, we propose that stress-induced facilitation of p-ERK2 in BLA is an important mechanism for the promoting influence of stress on the consolidation of contextual fear memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Resveratrol reverses diabetes-related decrement in sildenafil-induced relaxation of corpus cavernosum in aged rats.

    Science.gov (United States)

    Dalaklioglu, S; Bayram, Z; Tasatargil, A; Ozdem, S

    2017-06-01

    The aim of this study was to investigate the effect of resveratrol (RVT) on sildenafil-induced relaxations of isolated corpus cavernosum in non-diabetic and diabetic aged rats. A total of 13 male aged rats (72-80 weeks old) were randomized into two groups including non-diabetic aged rats and diabetic aged rats. Diabetes was induced in aged rats by streptozotocin (single i.p. dose of 45 mg/kg body weight) administration. At the end of the 12th week, corpus cavernosum strips of rats were suspended in an organ bath system. The corpus cavernosum relaxation was evaluated by sildenafil in the presence or absence of RVT (10 -4  M) for 45 min. Induction of diabetes resulted in significant inhibition of sildenafil-induced corpus cavernosum relaxation in aged rats. The diminished relaxation in response to sildenafil was significantly improved by acute RVT incubation in both non-diabetic and diabetic aged rats; however, the magnitude of potentiation induced by RVT was more pronounced in diabetic aged rats. The potentiating effect of RVT was significantly inhibited by L-NG-nitroarginine methyl ester (L-NAME, 10 -4  M, for 30 min) incubation in both groups. After the L-NAME incubation, the relaxation response of corporal tissues evoked by sildenafil was found to be similar in diabetic and non-diabetic aged rats. RVT improves sildenafil-induced relaxations of corpus cavernosum in both diabetic and non-diabetic aged rats probably by potentiating the activity of NOS, and this effect seems to be more manifest in diabetic aged group.

  6. Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study.

    Directory of Open Access Journals (Sweden)

    Sunil Joshi

    Full Text Available We have previously shown that production of reactive oxygen species (ROS is an important contributor to renal injury and inflammation following exposure to oxalate (Ox or calcium-oxalate (CaOx crystals. The present study was conducted, utilizing global transcriptome analyses, to determine the effect of Apocynin on changes in the NADPH oxidase system activated in kidneys of rats fed a diet leading to hyperoxaluria and CaOx crystal deposition.Age-, sex- and weight-matched rats were either fed regular rat chow or regular rat chow supplemented with 5% w/w hydroxy-L-proline (HLP. Half of the rats on the HLP diet were also placed on Apocynin-supplemented H(2O. After 28 days, each rat was euthanized, their kidneys freshly explanted and dissected to obtain both cortex and medulla tissues. Total RNA was extracted from each tissue and subjected to genomic microarrays to obtain global transcriptome data. KEGG was used to identify gene clusters with differentially expressed genes. Immunohistochemistry was used to confirm protein expressions of selected genes.Genes encoding both membrane- and cytosolic-NADPH oxidase complex-associated proteins, together with p21rac and Rap1a, were coordinately up-regulated significantly in both renal medulla and cortex tissues in the HLP-fed rats compared to normal healthy untreated controls. Activation of NADPH oxidase appears to occur via the angiotensin-II/angiotensin-II receptor-2 pathway, although the DAG-PKC pathway of neutrophils may also contribute. Immuno histochemical staining confirmed up-regulated gene expressions. Simultaneously, genes encoding ROS scavenger proteins were down-regulated. HLP-fed rats receiving Apocynin had a complete reversal in the differential-expression of the NADPH oxidase system genes, despite showing similar levels of hyperoxaluria.A strong up-regulation of an oxidative/respiratory burst involving the NADPH oxidase system, activated via the angiotensin-II and most likely the DAG

  7. Toxin ζ Reversible Induces Dormancy and Reduces the UDP-N-Acetylglucosamine Pool as One of the Protective Responses to Cope with Stress

    Directory of Open Access Journals (Sweden)

    Mariangela Tabone

    2014-09-01

    Full Text Available Toxins of the ζ/PezT family, found in the genome of major human pathogens, phosphorylate the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG leading to unreactive UNAG-3P. Transient over-expression of a PezT variant impairs cell wall biosynthesis and triggers autolysis in Escherichia coli. Conversely, physiological levels of ζ reversibly induce dormancy produce a sub-fraction of membrane-compromised cells, and a minor subpopulation of Bacillus subtilis cells become tolerant of toxin action. We report here that purified ζ is a strong UNAG-dependent ATPase, being GTP a lower competitor. In vitro, ζ toxin phosphorylates a fraction of UNAG. In vivo, ζ-mediated inactivation of UNAG by phosphorylation does not deplete the active UNAG pool, because expression of the toxin enhances the efficacy of genuine cell wall inhibitors (fosfomycin, vancomycin or ampicillin. Transient ζ expression together with fosfomycin treatment halt cell proliferation, but ε2 antitoxin expression facilitates the exit of ζ-induced dormancy, suggesting that there is sufficient UNAG for growth. We propose that ζ induces diverse cellular responses to cope with stress, being the reduction of the UNAG pool one among them. If the action of ζ is not inhibited, e.g., by de novo ε2 antitoxin synthesis, the toxin markedly enhances the efficacy of antimicrobial treatment without massive autolysis in Firmicutes.

  8. Reorganization of motor cortex and impairment of motor performance induced by hindlimb unloading are partially reversed by cortical IGF-1 administration.

    Science.gov (United States)

    Mysoet, Julien; Canu, Marie-Hélène; Gillet, Christophe; Fourneau, Julie; Garnier, Cyril; Bastide, Bruno; Dupont, Erwan

    2017-01-15

    Immobilization, bed rest, or sedentary lifestyle, are known to induce a profound impairment in sensorimotor performance. These alterations are due to a combination of peripheral and central factors. Previous data conducted on a rat model of disuse (hindlimb unloading, HU) have shown a profound reorganization of motor cortex and an impairment of motor performance. Recently, our interest was turned towards the role of insulin-like growth factor 1 (IGF-1) in cerebral plasticity since this growth factor is considered as the mediator of beneficial effects of exercise on the central nervous system, and its cortical level is decreased after a 14-day period of HU. In the present study, we attempted to determine whether a chronic subdural administration of IGF-1 in HU rats could prevent deleterious effects of HU on the motor cortex and on motor activity. We demonstrated that HU induces a shrinkage of hindlimb cortical representation and an increase in current threshold to elicit a movement. Administration of IGF-1 in HU rats partially reversed these changes. The functional evaluation revealed that IGF-1 prevents the decrease in spontaneous activity found in HU rats and the changes in hip kinematics during overground locomotion, but had no effect of challenged locomotion (ladder rung walking test). Taken together, these data clearly indicate the implication of IGF-1 in cortical plastic mechanisms and in behavioral alteration induced by a decreased in sensorimotor activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway.

    Science.gov (United States)

    Tiwari, Shashi Kant; Agarwal, Swati; Seth, Brashket; Yadav, Anuradha; Nair, Saumya; Bhatnagar, Priyanka; Karmakar, Madhumita; Kumari, Manisha; Chauhan, Lalit Kumar Singh; Patel, Devendra Kumar; Srivastava, Vikas; Singh, Dhirendra; Gupta, Shailendra Kumar; Tripathi, Anurag; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

    2014-01-28

    Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.

  10. Huntington's disease induced cardiac amyloidosis is reversed by modulating protein folding and oxidative stress pathways in the Drosophila heart.

    Science.gov (United States)

    Melkani, Girish C; Trujillo, Adriana S; Ramos, Raul; Bodmer, Rolf; Bernstein, Sanford I; Ocorr, Karen

    2013-01-01

    Amyloid-like inclusions have been associated with Huntington's disease (HD), which is caused by expanded polyglutamine repeats in the Huntingtin protein. HD patients exhibit a high incidence of cardiovascular events, presumably as a result of accumulation of toxic amyloid-like inclusions. We have generated a Drosophila model of cardiac amyloidosis that exhibits accumulation of PolyQ aggregates and oxidative stress in myocardial cells, upon heart-specific expression of Huntingtin protein fragments (Htt-PolyQ) with disease-causing poly-glutamine repeats (PolyQ-46, PolyQ-72, and PolyQ-102). Cardiac expression of GFP-tagged Htt-PolyQs resulted in PolyQ length-dependent functional defects that included increased incidence of arrhythmias and extreme cardiac dilation, accompanied by a significant decrease in contractility. Structural and ultrastructural analysis of the myocardial cells revealed reduced myofibrillar content, myofibrillar disorganization, mitochondrial defects and the presence of PolyQ-GFP positive aggregates. Cardiac-specific expression of disease causing Poly-Q also shortens lifespan of flies dramatically. To further confirm the involvement of oxidative stress or protein unfolding and to understand the mechanism of PolyQ induced cardiomyopathy, we co-expressed expanded PolyQ-72 with the antioxidant superoxide dismutase (SOD) or the myosin chaperone UNC-45. Co-expression of SOD suppressed PolyQ-72 induced mitochondrial defects and partially suppressed aggregation as well as myofibrillar disorganization. However, co-expression of UNC-45 dramatically suppressed PolyQ-72 induced aggregation and partially suppressed myofibrillar disorganization. Moreover, co-expression of both UNC-45 and SOD more efficiently suppressed GFP-positive aggregates, myofibrillar disorganization and physiological cardiac defects induced by PolyQ-72 than did either treatment alone. Our results demonstrate that mutant-PolyQ induces aggregates, disrupts the sarcomeric organization of

  11. Transgenic expression of Telomerase reverse transcriptase (Tert) improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell.

    Science.gov (United States)

    Hidema, Shizu; Fukuda, Tomokazu; Date, Shiori; Tokitake, Yuko; Matsui, Yasuhisa; Sasaki, Hiroki; Nishimori, Katsuhiko

    2016-10-01

    The enzymatic activity of telomerase is important for the extension of the telomere repeat sequence and overcoming cellular senescence. We generated a conditional transgenic mouse line, carrying the telomerase reverse transcriptase (Tert) expression cassette, controlled by the Cre-loxP-mediated recombination. In our study, Cre recombinase expression efficiently activated Tert expression, resulting in its increased enzymatic activity, which extended the period of cellular proliferation until the keratinocytes entered senescence. This suggests that transgenic Tert expression is effective in enhancing primary cell proliferation. Notably, Tert expression increased colony formation of induced pluripotent stem (iPS) cells after the introduction of four reprogramming factors, Oct-4, klf4, SOX-2, and c-Myc into the transgenic fibroblasts. To the best of our knowledge, this is the first study to show that the transgenic Tert expression enhances reprogramming efficiency of iPS cells, which indicates a critical role for Tert in the reprogramming process.

  12. Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology

    DEFF Research Database (Denmark)

    Egeblad, M; Mortensen, Ole Hartvig; Jäättelä, M

    2001-01-01

    Shedding of the extracellular domain of the ErbB2 tyrosine kinase receptor and expression of the remaining NH(2)-terminally truncated ErbB2 correlates with lymph node metastases and adverse outcome in human breast cancer. To study the possible signaling from such a truncated receptor, MCF-7 human...... breast cancer cells expressing NH(2)-terminally truncated ErbB2 (DeltaNErbB2) were compared with cells overexpressing wild-type ErbB2. Expression of DeltaNErbB2 in MCF-7 cells resulted in sustained activation of extracellular signal-regulated kinases (ERK) 1/2, extensive loss of the epithelial morphology......, appearance of vesicles and long protrusions as well as pronounced scattering of the cells. Similar alterations were observed upon ErbB2 overexpression but at much lower levels. Employing cell clones with inducible expression of DeltaNErbB2, it was revealed that the morphological changes were fully reversible...

  13. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au

    Science.gov (United States)

    Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

    2016-01-01

    We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction. PMID:28773549

  14. Reversible Changes in Resistance of Perovskite Nickelate NdNiO3 Thin Films Induced by Fluorine Substitution.

    Science.gov (United States)

    Onozuka, Tomoya; Chikamatsu, Akira; Katayama, Tsukasa; Hirose, Yasushi; Harayama, Isao; Sekiba, Daiichiro; Ikenaga, Eiji; Minohara, Makoto; Kumigashira, Hiroshi; Hasegawa, Tetsuya

    2017-03-29

    Perovskite nickel oxides are of fundamental as well as technological interest because they show large resistance modulation associated with phase transition as a function of the temperature and chemical composition. Here, the effects of fluorine doping in perovskite nickelate NdNiO 3 epitaxial thin films are investigated through a low-temperature reaction with polyvinylidene fluoride as the fluorine source. The fluorine content in the fluorinated NdNiO 3-x F x films is controlled with precision by varying the reaction time. The fully fluorinated film (x ≈ 1) is highly insulating and has a bandgap of 2.1 eV, in contrast to NdNiO 3 , which exhibits metallic transport properties. Hard X-ray photoelectron and soft X-ray absorption spectroscopies reveal the suppression of the density of states at the Fermi level as well as the reduction of nickel ions (valence state changes from +3 to +2) after fluorination, suggesting that the strong Coulombic repulsion in the Ni 3d orbitals associated with the fluorine substitution drives the metal-to-insulator transition. In addition, the resistivity of the fluorinated films recovers to the original value for NdNiO 3 after annealing in an oxygen atmosphere. By application of the reversible fluorination process to transition-metal oxides, the search for resistance-switching materials could be accelerated.

  15. Sex reversal induces size and performance differences among females of the African pygmy mouse,Mus minutoides.

    Science.gov (United States)

    Ginot, Samuel; Claude, Julien; Perez, Julie; Veyrunes, Frederic

    2017-06-01

    Differences in biological performance, at both intra- and inter-specific levels, have often been linked to morphology but seldom to behavioural or genotypic effects. We tested performance at the intraspecific level by measuring bite force in the African pygmy mouse, Mus minutoides. This species displays an unusual sex determination system, with sex-reversed, X*Y females carrying a feminizing X* chromosome. X*Y females cannot be differentiated from XX females based on external or gonadal morphology; however, they are known to be more aggressive. We found that bite force was higher in X*Y females than in other females and males. We then performed geometric morphometric analyses on their skulls and mandibles and found that the higher performance of X*Y females was mainly explained by a greater overall skull size. The effects of the X* chromosome thus go beyond feminization, and extend to whole-organism performance and morphology. Our results also suggest limited effects of behaviour on bite force. © 2017. Published by The Company of Biologists Ltd.

  16. Reversible naftifine-induced carotenoid depigmentation in Rhodotorula mucilaginosa (A. Jörg.) F.C. Harrison causing onychomycosis.

    Science.gov (United States)

    Moț, Augustin C; Pârvu, Marcel; Pârvu, Alina E; Roşca-Casian, Oana; Dina, Nicoleta E; Leopold, Nicolae; Silaghi-Dumitrescu, Radu; Mircea, Cristina

    2017-09-11

    Rhodotorula mucilaginosa was isolated from a patient with onychomycosis, and identification was confirmed by morphological and cultural characteristics as well as by DNA molecular analysis. Antifungal agents naftifine (10 mg/mL, active substance in Exoderil) and bifonazole (10 mg/mL, active substance in Canespor) were tested in different concentrations to assess in vitro effects on fungal growth and carotenoid synthesis. The antifungal mechanisms of action of naftifine and bifonazole against R. mucilaginosa isolates were similar and affected the biosynthetic pathway of ergosterol. For the first time, this research demonstrates that naftifine affects the carotenoid biosynthetic pathway, producing depigmentation of R. mucilaginosa in solid and liquid media. Furthermore, depigmentation was a reversible process; naftifine-treated yeast cells that were depigmented resumed carotenoid production upon transfer to fresh media. Raman and UV-vis spectrophotometry in conjunction with chromatographic analysis detected changes in carotenoids in yeast cells, with torulene decreasing and B-carotene increasing after repigmentation. Transmission electron micrographs revealed critical ultrastructural modifications in the depigmented cells after naftifine treatment, i.e., a low-electron-density cell wall without visible mucilage or lamellate structure.

  17. Spontaneous Reversibility of an Iatrogenic Orthodontic Elastic Band-induced Localized Periodontitis Following Surgical Intervention – Case Report

    OpenAIRE

    Nettem, Sowmya; Kumar Nettemu, Sunil; Kumar, Kiran; Reddy, Venkat; Siva Kumar, Pendyala

    2012-01-01

    Orthodontic elastic bands are an important iatrogenic etiologic factor in the causation of periodontal attachment apparatus breakdown. Appropriate diagnosis and a well constructed treatment plan tailor-made to suit the requirements of the particular patient is imperative for management of periodontal lesions induced by subgingival retention of rubber band. There are conflicting reports regarding the reattachment and regeneration of lost periodontal supporting tissues in such cases. The presen...

  18. Reversal of Cadmium-induced Oxidative Stress in Chicken by Herbal Adaptogens Withania Somnifera and Ocimum Sanctum

    OpenAIRE

    Bharavi, K.; Reddy, A. Gopala; Rao, G. S.; Reddy, A. Rajasekhara; Rao, S. V. Rama

    2010-01-01

    The present study was carried out to evaluate the herbal adaptogens Withania somnifera and Ocimum sanctum on cadmium-induced oxidative toxicity in broiler chicken. Cadmium administration at the rate of 100 ppm orally along with feed up to 28 days produced peroxidative damage, as indicated by increase in TBARS, reduction in glutathione (GSH) concentration in liver and kidney, and increase in catalase (CAT) and superoxide dismutase (SOD) of erythrocytes. Herbal adaptogens Withania somnifera roo...

  19. Normoxic Recovery Mimicking Treatment of Sleep Apnea Does Not Reverse Intermittent Hypoxia-Induced Bacterial Dysbiosis and Low-Grade Endotoxemia in Mice.

    Science.gov (United States)

    Moreno-Indias, Isabel; Torres, Marta; Sanchez-Alcoholado, Lidia; Cardona, Fernando; Almendros, Isaac; Gozal, David; Montserrat, Josep M; Queipo-Ortuño, Maria I; Farré, Ramon

    2016-10-01

    Intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) significantly modifies gut microbiota in mice. However, whether these IH-induced gut microbiome changes are reversible after restoring normal oxygenation (the equivalent of effective OSA therapy) is unknown. The aim of this study was to investigate gut microbiota composition and circulating endotoxemia after a post-IH normoxic period in a mouse model of OSA. Ten mice were subjected to IH (40 sec 21% O2-20 sec 5% O2) for 6 h/day for 6 w and 10 mice breathing normoxic air (NM) were used as controls. After exposures, both groups were subjected to 6 w in normoxia. Microbiome composition of fecal samples was determined by 16S ribosomal RNA (rRNA) pyrosequencing. Bioinformatic analysis was performed by Quantitative Insights into Microbial Ecology. Plasma lipopolysaccharide (LPS) levels were measured by endotoxin assay. After normoxic recovery, the Chao and Shannon indices of each group suggested similar bacterial richness and diversity. 16S rRNA pyrosequencing analysis showed that IH-exposed mice had a significant decrease in the abundance of Bacteroidetes and a significant increase of Firmicutes and Deferribacteres compared to the NM group. After normoxic recovery, circulating LPS concentrations were higher in the IH group (P < 0.009). Moreover, the IH group showed a negative and significant correlation between the abundance of Lactobacillus and Ruminococcus and significant positive correlations between the abundance of Mucispirillum and Desulfovibrio and plasma LPS levels, respectively. Even after prolonged normoxic recovery after IH exposures, gut microbiota and circulating endotoxemia remain negatively altered, suggesting that potential benefits of OSA treatment for reversing OSA-induced changes in gut microbiota may either require a longer period or alternative interventions. © 2016 Associated Professional Sleep Societies, LLC.

  20. Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: implications for clinical trials in Alzheimer's disease.

    Science.gov (United States)

    Savory, J; Huang, Y; Wills, M R; Herman, M M

    1998-04-01

    A clinical trial in patients with Alzheimer's disease has indicated that frequent intramuscular (i.m.) treatment with desferrioxamine (DFO) slows progression of the disease. Confirmatory trials have not been carried out, partly because of the rigors of twice daily intramuscular injections over a period of 2 years, even though the initial report gave promising results. The aim of the present study was to determine an optimal DFO treatment protocol in an animal model exhibiting Alzheimer's-like intraneuronal protein aggregates, previously shown to be partially reversed by such treatment. New Zealand white rabbits were injected intracisternally with either aluminum (Al) maltolate or with saline on day 0. Intramuscular injections of DFO were given to selected rabbits for 2 days prior to sacrifice on days 4, 6 or 8. Bielschowsky's silver impregnation demonstrated widespread neurofibrillary degeneration (NFD) in neuronal cell bodies and neurites of brain and spinal cord from Al-treated rabbits. Monoclonal antibodies Tau-2, AT8, PHF-1 and Alz-50, all of which characteristically stain neurofibrillary tangles associated with Alzheimer's disease, strongly labeled the Al-induced NFD. The number of positive neurons and staining intensities were much less in rabbits treated with Al and subsequently with DFO, than in animals only given Al. Control rabbit receiving intracisternal saline were negative for NFD. The results of quantitative immunohistochemistry using image analysis confirmed that immunostaining densities with all tau mAbs were higher in Al-treated than in Al-DFO-treated or in saline-treated controls. Furthermore, it appears that hyperphosphorylation of tau does not make this protein resistant to degradation once Al has been removed by DFO treatment. The effectiveness of only two days of DFO treatment in reversing Al-induced neurofibrillary degeneration suggests that further clinical trials of DFO for treatment of Alzheimer's disease should be attempted using much

  1. Melatonin Reverses Fas, E2F-1 and Endoplasmic Reticulum Stress Mediated Apoptosis and Dysregulation of Autophagy Induced by the Herbicide Atrazine in Murine Splenocytes.

    Directory of Open Access Journals (Sweden)

    Shweta Sharma

    Full Text Available Exposure to the herbicide Atrazine (ATR can cause immunotoxicity, apart from other adverse consequences for animal and human health. We aimed at elucidating the apoptotic mechanisms involved in immunotoxicity of ATR and their attenuation by Melatonin (MEL. Young Swiss mice were divided into control, ATR and MEL+ATR groups based on daily (x14 intraperitoneal administration of the vehicle (normal saline, ATR (100 mg/kg body weight and MEL (20 mg/kg body weight with ATR. Isolated splenocytes were processed for detection of apoptosis by Annexin V-FITC and TUNEL assays, and endoplasmic reticulum (ER stress by immunostaining. Key proteins involved in apoptosis, ER stress and autophagy were quantified by immunoblotting. ATR treatment resulted in Fas-mediated activation of caspases 8 and 3 and inactivation of PARP1 which were inhibited significantly by co-treatment with MEL. MEL also attenuated the ATR-induced, p53 independent mitochondrial apoptosis through upregulation of E2F-1 and PUMA and suppression of their downstream target Bax. An excessive ER stress triggered by ATR through overexpression of ATF-6α, spliced XBP-1, CREB-2 and GADD153 signals was reversed by MEL. MEL also reversed the ATR-induced impairment of autophagy which was indicated by a decline in BECN-1, along with significant enhancement in LC3B-II and p62 expressions. Induction of mitochondrial apoptosis, ER stress and autophagy dysregulation provide a new insight into the mechanism of ATR immunotoxicity. The cytoprotective role of MEL, on the other hand, was defined by attenuation of ER stress, Fas-mediated and p53 independent mitochondria-mediated apoptosis as well as autophagy signals.

  2. Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice.

    Science.gov (United States)

    Latres, Esther; Pangilinan, Jeffrey; Miloscio, Lawrence; Bauerlein, Roy; Na, Erqian; Potocky, Terra B; Huang, Ying; Eckersdorff, Mark; Rafique, Ashique; Mastaitis, Jason; Lin, Calvin; Murphy, Andrew J; Yancopoulos, George D; Gromada, Jesper; Stitt, Trevor

    2015-01-01

    Loss of skeletal muscle mass and function in humans is associated with significant morbidity and mortality. The role of myostatin as a key negative regulator of skeletal muscle mass and function has supported the concept that inactivation of myostatin could be a useful approach for treating muscle wasting diseases. We generated a myostatin monoclonal blocking antibody (REGN1033) and characterized its effects in vitro using surface plasmon resonance biacore and cell-based Smad2/3 signaling assays. REGN1033 was tested in mice for the ability to induce skeletal muscle hypertrophy and prevent atrophy induced by immobilization, hindlimb suspension, or dexamethasone. The effect of REGN1033 on exercise training was tested in aged mice. Messenger RNA sequencing, immunohistochemistry, and ex vivo force measurements were performed on skeletal muscle samples from REGN1033-treated mice. The human monoclonal antibody REGN1033 is a specific and potent myostatin antagonist. Chronic treatment of mice with REGN1033 increased muscle fiber size, muscle mass, and force production. REGN1033 prevented the loss of muscle mass induced by immobilization, glucocorticoid treatment, or hindlimb unweighting and increased the gain of muscle mass during recovery from pre-existing atrophy. In aged mice, REGN1033 increased muscle mass and strength and improved physical performance during treadmill exercise. We show that specific myostatin antagonism with the human antibody REGN1033 enhanced muscle mass and function in young and aged mice and had beneficial effects in models of skeletal muscle atrophy.

  3. Sex Reversal in Birds.

    Science.gov (United States)

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  4. Moderate calorie restriction to achieve normal weight reverses β-cell dysfunction in diet-induced obese mice: involvement of autophagy.

    Science.gov (United States)

    Gao, Xiuying; Yan, Dien; Zhao, Yinan; Tao, Hong; Zhou, Yingsheng

    2015-01-01

    Severe calorie restriction (CR) is shown to improve or even reverse β-cell dysfunction in patients with obesity and type 2 diabetes mellitus. However, whether mild to moderate CR can reverse β-cell dysfunction induced by obesity and the underlying mechanism remain unclear. Autophagy plays an important role in maintaining mass, architecture and function of β-cells. While the impact of CR on β-cell autophagy is unknown. This study aims to investigate the effects of moderate CR on β-cell function and autophagy activity in diet-induced obese (DIO) mice. DIO C57BL/6 mice were subjected to 3 weeks of switching to normal chow (HF → NC group) or normal chow with 40 % CR (HF → NC CR group). Then hematoxylin-eosin and immunohistochemistry staining were performed to observe β-cell morphology. β-cell function was evaluated by intraperitoneal glucose tolerance test in vivo and static GSIS (glucose-stimulated insulin secretion) in isolated islets. β-cell autophagy activity was determined by transmission electron microscope and western blot. In the HF → NC CR group, CR normalized body weights, completely restored glucose tolerance, early-phase and second-phase insulin secretion, insulin sensitivity, and islet size. CR also normalized insulin content and glucose-stimulated insulin secretion in isolated islets in vitro. Furthermore, β-cell autophagy level was increased in the HF → NC CR group, but AMPK phosphorylation remained unchanged. Although HF → NC mice achieved moderate weight loss and normal glucose tolerance, their insulin secretion was not improved compared with obese control mice, and additionally, β-cell autophagy was not activated in these mice. Moderate (40 %) CR to achieve normal weight reversed β-cell dysfunction and insulin resistance, and restored glucose homeostasis in DIO mice. Furthermore, the up-regulation of β-cell autophagy may play a role in this process, independent of AMPK activation.

  5. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation.

    Science.gov (United States)

    Reddy, Aravind T; Lakshmi, Sowmya P; Muchumarri, Ramamohan R; Reddy, Raju C

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs' electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease.

  6. Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

    International Nuclear Information System (INIS)

    Zhu Hanneng; Chen Wenying; Xiong Sidong

    2000-01-01

    Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

  7. Virus-induced gene silencing (VIGS) as a reverse genetic tool to study development of symbiotic root nodules

    DEFF Research Database (Denmark)

    Kjær, Gabriela Didina Constantin; Grønlund, Mette; Stougaard, Jens

    2008-01-01

    Virus-induced gene silencing (VIGS) can provide a shortcut to plants with altered expression of specific genes. Here, we report that VIGS of the Nodule inception gene (Nin) can alter the nodulation phenotype and Nin gene expression in Pisum sativum. PsNin was chosen as target because of the disti......NinB, nodulation was reduced by at least 45%. Down-regulation of PsNin transcripts in plants inoculated with vectors carrying PsNin cDNA fragments was confirmed and these plants displayed a relative increase in the root/shoot ratio, as expected if nitrogen fixation had been impaired....

  8. Reverse Osmosis

    Indian Academy of Sciences (India)

    or the water reaches the tip of every leaf of a plant is due to osmotic pressure. ... concentration and temperature of the solution by a law that is similar to the gas law. ... waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis, desalinatiion, seawater, water purification.

  9. Rutin reverses radiation-induced oxidative DNA damage and inflammation through the modulation of p38/Nf-Kb and Keap1/Nrf2 pathway

    International Nuclear Information System (INIS)

    Manna, Krishnendu; Khan, Amitava; Biswas, Sushobhan; Das, Ujjal; Sengupta, Aaveri; Dey, Sanjit; Chakraborty, Anindita

    2016-01-01

    Rutin (RU), widely known plant polyphenol, possesses wide range of biological activities. In this study, we evaluated the effect of RU on radiation (IR)-induced oxidative stress and inflammation in murine liver and explored the potential mechanisms underlying this effect. Swiss albino mice were subjected to oral pretreatment of RU (75 mg/kg body weight) for three consecutive days before irradiation (6 Gy). Plethora of biochemical indices were carried out to determine the hepato protective effect of RU. Molecular mechanism of action was also assessed through employing the immunoblot, flow cytometry and immunofluorescence techniques. Hepatoprotective effects of RU were associated with the upregulation of antioxidant enzyme activities (SOD, catalase and GSH) and down regulation of serum toxicity markers (ALT, AST and LDH). Results also demonstrated that RU significantly down regulated the levels of hepatic inflammatory markers like TNF-α, IL-6 and expressions of p38-MAPK, NF-κB, iNOS and COX-2. Histopathological changes further confirmed the biochemical and immunohistochemical results showing that IR caused significant structural damage to liver which were reversed by pretreatment of RU. RU also significantly suppressed the IR-induced activation of Keap1 and modulated the phosphorylation of PI3K/AKT. Further, pretreatment with RU augmented the expression of Nrf2 thereby enhancing the activity of downstream phase-2 detoxifying hepatic enzymes (HO-1, NQO-1, GST and Mn-SOD) which altered the IR-induced oxidative imbalance. The present results is evidence based mechanism that RU remained a promising radioprotector in attenuating IR-induced oxidative stress, inflammation and hepatotoxicity through the modulation of Nrf2/HO-1 and p38 /NF-κB signaling pathway. (author)

  10. Large intergenic non-coding RNA-ROR reverses gemcitabine-induced autophagy and apoptosis in breast cancer cells.

    Science.gov (United States)

    Chen, Yao-Min; Liu, Yu; Wei, Hai-Yan; Lv, Ke-Zhen; Fu, Pei-Fen

    2016-09-13

    The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/β-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.

  11. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    Science.gov (United States)

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Influence of acid-induced conformational variability on protein separation in reversed phase high performance liquid chromatography.

    Science.gov (United States)

    Bobály, Balázs; Tóth, Eszter; Drahos, László; Zsila, Ferenc; Visy, Júlia; Fekete, Jenő; Vékey, Károly

    2014-01-17

    Influence of acid concentration in the mobile phase on protein separation was studied in a wide concentration range using trifluoroacetic acid (TFA) and formic acid (FA). At low, 0.001-0.01 (v/v%) TFA concentration and appropriate solvent strength proteins elute before the column's dead time. This is explained by the proteins having a structured, but relatively extended conformation in the eluent; and are excluded from the pores of the stationary phase. Above ca. 0.01-0.05 (v/v%) TFA concentration proteins undergo further conformational change, leading to a compact, molten globule-like structure, likely stabilized by ion pairing. Proteins in this conformation enter the pores and are retained on the column. The results suggest a pore exclusion induced separation related to protein conformation. This effect is influenced by the pH and type of acid used, and is likely to involve ion-pair formation. The TFA concentration needed to result in protein folding (and therefore to observe retention on the column) depends on the protein; and therefore can be utilized to improve chromatographic performance. Conformation change was monitored by circular dichroism spectroscopy and mass spectrometry; and it was shown that not only TFA but FA can also induce molten globule formation. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs.

    Science.gov (United States)

    Savio, L E B; Vuaden, F C; Kist, L W; Pereira, T C; Rosemberg, D B; Bogo, M R; Bonan, C D; Wyse, A T S

    2013-10-10

    Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic dysfunction in patients with type 2 diabetes and renal disease.

    Science.gov (United States)

    Esposito, Pasquale; Mereu, Roberto; De Barbieri, Giacomo; Rampino, Teresa; Di Toro, Alessandro; Groop, Per-Henrik; Dal Canton, Antonio; Bernardi, Luciano

    2016-04-01

    Cardiovascular autonomic dysfunction, evaluated as baroreflex sensitivity (BRS), could be acutely corrected by slow breathing or oxygen administration in patients with type 1 diabetes, thus suggesting a functional component of the disorder. We tested this hypothesis in patients with the type 2 diabetes with or without renal impairment. Twenty-six patients with type 2 diabetes (aged 61.0 ± 0.8 years, mean ± SEM; duration of diabetes 10.5 ± 2 years, BMI 29.9 ± 0.7 kg/m(2), GFR 68.1 ± 5.6 ml/min) and 24 healthy controls (aged 58.5 ± 1.0 years) were studied. BRS was obtained from recordings of RR interval and systolic blood pressure fluctuations during spontaneous and during slow, deep (6 breaths/min) controlled breathing in conditions of normoxia or hyperoxia (5 l/min oxygen). During spontaneous breathing, diabetic patients had lower RR interval and lower BRS compared with the control subjects (7.1 ± 1.2 vs. 12.6 ± 2.0 ms/mmHg, p breathing and oxygen administration significantly increased arterial saturation, reduced RR interval and increased BRS in both groups (to 9.6 ± 1.8 and 15.4 ± 2.4 ms/mmHg, respectively, p breathing and hyperoxia (p breathing during normoxia). Autonomic dysfunction present in patients with type 2 diabetes can be partially reversed by slow breathing, suggesting a functional role of hypoxia, also in patients with DKD. Interventions known to relieve tissue hypoxia and improve autonomic function, like physical activity, may be useful in the prevention and management of complications in patients with diabetes.

  15. First molecular identification of the vertebrate hosts of Culicoides imicola in Europe and a review of its blood-feeding patterns worldwide: implications for the transmission of bluetongue disease and African horse sickness.

    Science.gov (United States)

    Martínez-DE LA Puente, J; Navarro, J; Ferraguti, M; Soriguer, R; Figuerola, J

    2017-12-01

    Culicoides (Diptera: Ceratopogonidae) are vectors of pathogens that affect wildlife, livestock and, occasionally, humans. Culicoides imicola (Kieffer, 1913) is considered to be the main vector of the pathogens that cause bluetongue disease (BT) and African horse sickness (AHS) in southern Europe. The study of blood-feeding patterns in Culicoides is an essential step towards understanding the epidemiology of these pathogens. Molecular tools that increase the accuracy and sensitivity of traditional methods have been developed to identify the hosts of potential insect vectors. However, to the present group's knowledge, molecular studies that identify the hosts of C. imicola in Europe are lacking. The present study genetically characterizes the barcoding region of C. imicola trapped on farms in southern Spain and identifies its vertebrate hosts in the area. The report also reviews available information on the blood-feeding patterns of C. imicola worldwide. Culicoides imicola from Spain feed on blood of six mammals that include species known to be hosts of the BT and AHS viruses. This study provides evidence of the importance of livestock as sources of bloodmeals for C. imicola and the relevance of this species in the transmission of BT and AHS viruses in Europe. © 2017 The Royal Entomological Society.

  16. Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Kang

    2013-01-01

    Full Text Available The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC patients harboring epidermal growth factor receptor- (EGFR- activating mutation. However, the inevitable recurrence resulting from acquired resistance has limited the clinical improvement in therapy outcomes. Many studies demonstrate that hepatocyte growth factor- (HGF- Met axis plays an important role in tumor progression and drug sensitivity. HGF may induce resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt signaling. The purpose of this study was to determine whether bufalin, a major bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827, and H1975. Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These results suggested that bufalin might have a potential to overcome HGF-induced resistance to molecular-targeted drugs for lung cancer.

  17. Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

    DEFF Research Database (Denmark)

    Jensen, J B; Pickering, D S; Schousboe, A

    2000-01-01

    Cultured neocortical neurons, which predominantly consist of GABAergic neurons exhibit a pronounced stimulus-coupled GABA release. Since the cultures may contain a small population of glutamatergic neurons and the GABAergic neurons have a high content of glutamate it was of interest to examine...... if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4......-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium...

  18. Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa; An autoradiographic study using tritiated thymidine

    Energy Technology Data Exchange (ETDEWEB)

    Tielemans, Y.; Chen, D.; Sundler, F.; Haakanson, R.; Willems, G. (Vrije Univ., Brussels (Belgium))

    1992-01-01

    Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. The authors studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, wheras it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa. 33 refs., 6 figs.

  19. GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta.

    Science.gov (United States)

    Yao, Guo; Zhang, Yafang; Wang, Di; Yang, Ruirui; Sang, Hui; Han, Linlin; Zhu, Yuexia; Lu, Yanyan; Tan, Yeke; Shang, Zhanping

    2017-01-01

    To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR. In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (pmacrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia.

  20. Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.

    Science.gov (United States)

    Yu, Lixia; Chen, Yuan; Wang, Weiguang; Xiao, Zhonghai; Hong, Yan

    2016-08-04

    Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

  1. Reversal of TMS-induced motor twitch by training is associated with a reduction in excitability of the antagonist muscle

    Directory of Open Access Journals (Sweden)

    Fregni Felipe

    2011-08-01

    Full Text Available Abstract Background A single session of isolated repetitive movements of the thumb can alter the response to transcranial magnetic stimulation (TMS, such that the related muscle twitch measured post-training occurs in the trained direction. This response is attributed to transient excitability changes in primary motor cortex (M1 that form the early part of learning. We investigated; (1 whether this phenomenon might occur for movements at the wrist, and (2 how specific TMS activation patterns of opposing muscles underlie the practice-induced change in direction. Methods We used single-pulse suprathreshold TMS over the M1 forearm area, to evoke wrist movements in 20 healthy subjects. We measured the preferential direction of the TMS-induced twitch in both the sagittal and coronal plane using an optical goniometer fixed to the dorsum of the wrist, and recorded electromyographic (EMG activity from the flexor carpi radialis (FCR and extensor carpi radialis (ECR muscles. Subjects performed gentle voluntary movements, in the direction opposite to the initial twitch for 5 minutes at 0.2 Hz. We collected motor evoked potentials (MEPs elicited by TMS at baseline and for 10 minutes after training. Results Repetitive motor training was sufficient for TMS to evoke movements in the practiced direction opposite to the original twitch. For most subjects the effect of the newly-acquired direction was retained for at least 10 minutes before reverting to the original. Importantly, the direction change of the movement was associated with a significant decrease in MEP amplitude of the antagonist to the trained muscle, rather than an increase in MEP amplitude of the trained muscle. Conclusions These results demonstrate for the first time that a TMS-twitch direction change following a simple practice paradigm may result from reduced corticospinal drive to muscles antagonizing the trained direction. Such findings may have implications for training paradigms in

  2. The effect of CA1 α2 adrenergic receptors on memory retention deficit induced by total sleep deprivation and the reversal of circadian rhythm in a rat model.

    Science.gov (United States)

    Norozpour, Yaser; Nasehi, Mohammad; Sabouri-Khanghah, Vahid; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza

    2016-09-01

    The α2 adrenergic receptors which abundantly express in the CA1 region of the hippocampus play an important role in the regulation of sleep and memory retention processes. Based on the available evidence, the aim of our study was to investigate consequences of the activation and deactivation of CA1 α2 adrenergic receptors (by clonidine and yohimbine, respectively) on the impairment of memory retention induced by total sleep deprivation (TSD) and the reversal of circadian rhythm (RCR) in a rat model. To this end, the water box apparatus and passive avoidance task were in turn used to induce sleep deprivation and assess memory retention. Our findings suggested that TSD (for 24 and 36, but not 12h) and RCR (12h/day for 3 consecutive days) impair memory function. The post-training intra-CA1 administration of yohimbine (α2 adrenergic receptor antagonist) on its own, at the dose of 0.1μg/rat, decreased the step-through latency and locomotor activity in the TSD- sham treated but not undisturbed sleep rats. Unlike yohimbine, clonidine (α2 adrenergic receptor agonist), in all applied doses (0.001, 0.01 and 0.1μg/rat), failed to induce such an effect. While the subthreshold dose of yohimbine (0.001μg/rat) abrogated the impairment of memory retention induced by the 24-h TSD, it could potentiate the impairment of memory retention induced by 36-h TSD, suggesting the modulatory effect of yohimbine. Moreover, the subthreshold dose of clonidine (0.1μg/rat) restored the memory retention deficit in TSD rats (24 and 36h). On the other hand, the subthreshold dose of clonidine (0.1μg/rat), but not yohimbine (0.001μg/rat) restored the memory retention deficit in RCR rats. Such interventions however did not alter the locomotor activity. The above observations proposed that CA1 α2 adrenergic receptors play a potential role in memory retention deficits induced by TSD and RCR. Copyright © 2016. Published by Elsevier Inc.

  3. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... by accounting for the significance of the materials and the equipment that enters into the production of statistics. Key words: Reversible statistics, diverse materials, constructivism, economics, science, and technology....

  4. L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines.

    Science.gov (United States)

    Chiu, Ling-Yen; Ko, Jiunn-Liang; Lee, Yi-Ju; Yang, Tsung-Ying; Tee, Yi-Torng; Sheu, Gwo-Tarng

    2010-02-15

    Multidrug resistance (MDR) of cancer cells to cytotoxic drugs significantly impedes chemotherapeutic treatment. The purpose of this study is to characterize docetaxel (DOC) or vincristine (VCR) selected A549 and H1299 non-small cell lung cancer (NSCLC) sublines that exhibit MDR phenotypes and followed by re-sensitization study. Although all drug resistant sublines showed cross-resistance to DOC, VCR, and doxorubicin (DXR), the expression of ATP-binding cassette (ABC) transporter B1 (ABCB1) gene was found to be strongly induced in DOC but not in VCR resistant A549 sublines by quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR). In DOC and VCR resistant H1299 sublines, moderate expression of ABCB1 was detected. The levels of ABCB1 protein and efflux activities were further examined by immunoblotting and rhodamin-123 staining assay. The results showed that both ABC and non-ABC mediated MDR are existed. Furthermore, verapamil (VER), an inhibitor of ABCB1 and an L-type calcium channel blocker, is capable of reversing the resistance in all drug-resistant sublines independent of ABCB1 expression. Importantly, VER only sensitizes resistant sublines but has no effect on parental cancer cells. Other L-type calcium channel blockers, such as diltiazem (DIL) and nifedipine (NIF), also sensitize MDR sublines without interfering with ABCB1 activity but with lower efficacy than VER. Our data showed that in addition to ABCB1, calcium channel activity may play a crucial role in DOC- and VCR-acquired MDR. Therefore, inhibition of calcium influx may provide a new target to modulate MDR in chemotherapy. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  5. Effects of exogenous ATM gene on mRNA expression of human telomerase reverse transcriptase in AT cells induced by irradiation

    International Nuclear Information System (INIS)

    Sheng Fangjun; Cao Jianping; Luo Jialin; Zhu Wei; Liu Fenju; Feng Shuang; Song Jianyuan; Li Chong

    2005-01-01

    The study is to observe effects of exogenous ATM gene on mRNA expression of hTERT (human telomerase reverse transcriptase) in fibroblast cells (AT5BIVA cells) from skin of Ataxia-telangiectasia (AT) patients and to study the regulation of ATM to hTERT. Using reverse transcription polymerase chain reaction (RT-PCR), mRNA expression of hTERT in AT, PEBS7-AT, ATM + -AT and GM cells irradiated with 0 and 3 Gy of 60 Co γ-rays were examined respectively. The difference of the mRNA expression of hTERT among AT, PEBS7-AT, ATM + -AT and GM cells were analyzed. Difference of the mRNA expression of hTERT between 0 Gy and 3 Gy groups was analyzed, too. The results showed that the mRNA expression of hTERT in GM cells was negative, but positive mRNA expression of hTERT in AT cells. The mRNA expression of hTERT in ATM + -AT cells decreased significantly (p 60 Co γ-rays, the mRNA expression of hTERT in GM cells was positive, and that in AT, PEBS7-AT, ATM + -AT cells was increased (p + -AT cells was lower than that in AT and PEBS7-AT cells respectively (p<0.05). It is postulated that exogenous ATM is able to downregulate the mRNA expression of hTERT in AT cells, ionizing radiation can induce the mRNA expression of hTERT in cells and telomerase anticipates the repair of damaged DNA. (authors)

  6. Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

    Directory of Open Access Journals (Sweden)

    Hilda Vargas-Robles

    2015-01-01

    Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  7. Reverse plasticity: TGF-β and IL-6 induce Th1-to-Th17-cell transdifferentiation in the gut.

    Science.gov (United States)

    Geginat, Jens; Paroni, Moira; Kastirr, Ilko; Larghi, Paola; Pagani, Massimiliano; Abrignani, Sergio

    2016-10-01

    Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells. Thus, IFN-γ-producing Th1 effector cells specific for an intestinal microbial antigen were shown to acquire IL-17-producing capacities in the gut in a mouse model of colitis, and in response to TGF-β and IL-6 in vitro. TGF-β induced Runx1, and together with IL-6 was shown to render the ROR-γt and IL-17 promoters in Th1 cells accessible for Runx1 binding. In this commentary, we discuss how this unexpected plasticity of Th1 cells challenges our view on the generation of Th1/17 cells with the capacity to co-produce IL-17 and IFN-γ, and consider possible implications of this Th1-to-Th17-cell conversion for therapies of inflammatory bowel diseases and protective immune responses against intracellular pathogens. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Role of Extracorporeal Membrane Oxygenation in Aluminum Phosphide Poisoning-Induced Reversible Myocardial Dysfunction: A Novel Therapeutic Modality.

    Science.gov (United States)

    Mohan, Bishav; Gupta, Vivek; Ralhan, Sarju; Gupta, Dinesh; Puri, Sandeep; Wander, Gurpreet Singh; Singh, Bhupinder

    2015-11-01

    Aluminum phosphide (AlP) poisoning carries a high rate of mortality despite intensive care management, primarily because of refractory myocardial depression, resistant hypotension, and severe metabolic acidosis as well as acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a modified "heart-lung" machine to provide temporary cardiorespiratory support. We studied the novel use of ECMO in the management of a subset of patients with AlP poisoning. In this case series, seven patients with AlP poisoning suffering from severe metabolic acidosis and refractory cardiogenic shock with a reduced left ventricular ejection fraction (poisoning-induced severe metabolic acidosis and refractory cardiogenic shock may lead to a significant improvement in overall survival. Therefore, ECMO might be considered as a bridge therapy for patients with intractable cardiorespiratory failure caused by AlP poisoning who are not responding to conventional treatment. ECMO, however, also is associated with significant complication rates, which must be incorporated into the risk-benefit analysis while considering treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Exercise reverses OVA-induced inhibition of glucocorticoid receptor and increases anti-inflammatory cytokines in asthma.

    Science.gov (United States)

    Silva, R A; Almeida, F M; Olivo, C R; Saraiva-Romanholo, B M; Martins, M A; Carvalho, C R F

    2016-01-01

    The purpose of this study was to determine the effect of aerobic exercise training (AT) on the expression of glucocorticoid receptors (GR) and anti-inflammatory cytokines in an asthma model. BALB/c mice were divided into groups control (CT; nonsensitized/nontrained), aerobic training (AT; nonsensitized/trained), ovalbumin (OVA; sensitized/not trained), and OVA+AT (sensitized/trained). OVA groups received OVA by inhalation, and the AT groups completed 1, 3, or 7 days of exercise (60 min/session). Expression of GR, IL-4, IL-5, IL-10, IL-1ra, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1; eosinophils counting; and airway remodeling (AR) features [airway smooth muscle (ASM) and epithelial thickness and collagen fiber deposition] were quantified. OVA sensitization induced a decrease in the expression of GR and increases in the eosinophil, IL-4, IL-5, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1, and AR features (P asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, Camila P., E-mail: mila_bonin@yahoo.com.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil); Baccarin, Raquel Y.A., E-mail: baccarin@usp.br [Department of Clinics, School of Veterinary Medicine, University of São Paulo, São Paulo 05508-900 (Brazil); Nostell, Katarina, E-mail: katarina.nostell@slu.se [Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07 Uppsala (Sweden); Nahum, Laila A., E-mail: laila@nahum.com.br [Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002 (Brazil); Faculdade Infórium de Tecnologia, Belo Horizonte 30130-180 (Brazil); Fossum, Caroline, E-mail: caroline.fossum@bvf.slu.se [Department of Biomedicine and Veterinary Public Health, Section for Immunology, Swedish University of Agricultural Sciences, BMC, Box 588, SE 751 23 Uppsala (Sweden); Camargo, Maristela M. de, E-mail: mmcamar@usp.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil)

    2013-03-08

    Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.

  11. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

    Science.gov (United States)

    Neelakantan, Harshini; Vance, Virginia; Wetzel, Michael D; Wang, Hua-Yu Leo; McHardy, Stanton F; Finnerty, Celeste C; Hommel, Jonathan D; Watowich, Stanley J

    2018-01-01

    reverse diet-induced obesity and validate NNMT as a viable target to treat obesity and related metabolic conditions. Increased flux of key cellular energy regulators, including NAD + and SAM, may potentially define the therapeutic mechanism-of-action of NNMT inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

    International Nuclear Information System (INIS)

    Bonin, Camila P.; Baccarin, Raquel Y.A.; Nostell, Katarina; Nahum, Laila A.; Fossum, Caroline; Camargo, Maristela M. de

    2013-01-01

    Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2

  13. An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2013-11-01

    Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage. Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and

  14. Reversal of an aluminium induced alteration in redox status in different regions of rat brain by administration of centrophenoxine.

    Science.gov (United States)

    Nehru, Bimla; Bhalla, Punita

    2006-10-01

    Aluminium is one of the most studied neurotoxin, and its effects on nervous system are both structural and functional, involving various regions of brain. Aluminium toxicity is known to have multiple mechanisms of action in the central nervous system. Affinity of aluminium for thiol substrates is considered a possible molecular mechanism involved in aluminium neurotoxicity. The reduced glutathione (GSH) is especially important for cellular defence against aluminium toxicity. This study pertains to the modulatory action of centrophenoxine on GSH status in aluminium exposed different brain regions of the female rats. Aluminium was administered orally at a dose of 40 mg/Kg x b x wt x /day for a period of eight weeks whereas, centrophenoxine was administered intraperitoneally at a dose of 100 mg/Kg x b x wt x /day for a period of six weeks. The study was carried out in different regions of brain namely cerebrum, cerebellum, medulla oblongata and hypothalamus. Animals exposed to aluminum, registered a significant decrease in the levels of reduced glutathione, and oxidized glutathione as well as in the activity of glutathione reductase in all the different regions studied when compared to normal control animals. Post-treatment with centrophenoxine, showed a significant improvement in the thiol levels in different regions. Centrophenoxine when administered alone also had a profound effect on the levels of reduced glutathione as well as on the activity of glutathione reductase. From the present results, it can be stated that centrophenoxine administration, as a thiol-antioxidant, arrests the aluminium induced cellular damage by improving the thiol status in brain regions.

  15. Reversal of drug-induced gingival overgrowth by UV-mediated apoptosis of gingival fibroblasts - an in vitro study.

    Science.gov (United States)

    Ritchhart, Casey; Joy, Anita

    2018-02-07

    Gingival overgrowth (GO) is an undesirable result of certain drugs like Cyclosporine A (CsA). Histopathology of GO shows hyperplasia of gingival epithelium, expansion of connective tissue with increased collagen, or a combination. Factors such as age, gender, oral hygiene, duration, and dosage also influence onset and severity of GO. One of the mechanisms behind uncontrolled cell proliferation in drug-induced GO is inhibition of apoptotic pathways, with a consequent effect on normal cell turnover. Our objective was to determine if UV photo-treatment would activate apoptosis in the gingival fibroblast component. Human gingival fibroblast cells (HGF-1) were exposed to 200ng/ml or 400ng/ml CsA and maintained for 3, 6, and 9 days, followed by UV radiation for 2, 5, or 10min (N=6). Naïve (no CsA or UV), negative (UV, no CsA), and positive controls (CsA, no UV) were designated. Prior to UV treatment, growth media was replaced with 1M PBS to prevent absorption of UV radiation by serum proteins, and cells were incubated in growth media for 24h post-UV before processing for TUNEL assay, cell proliferation assays, or immunofluorescence. Data showed a temporal increase in proliferation of HGF-1 cells under the influence of CsA. The 200ng/ml dose was more effective in causing over-proliferation. UV treatment for 10min resulted in significant reduction in cell numbers, as evidenced by counts and proliferation assays. Our study is a first step to further evaluate UV-mediated apoptosis as a mechanism to control certain forms of GO. Copyright © 2018 Elsevier GmbH. All rights reserved.

  16. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

    Directory of Open Access Journals (Sweden)

    Joep P M Derikx

    . At the same time, M30 immunoreactivity was absent in intact epithelial lining. CONCLUSIONS: This is the first human study to clarify intestinal IR induced cell damage and repair and its direct consequences. It reveals a unique, endogenous clearing mechanism for injured enterocytes: rapid detachment of damaged apoptotic enterocytes into the lumen. This process is followed by repair of the epithelial continuity within an hour, resulting in a normal epithelial lining.

  17. Magnetic Field-Induced Reverse Martensitic Transformation and Thermal Transformation Arrest Phenomenon of Ni41Co9Mn39Sb11 Alloy

    Directory of Open Access Journals (Sweden)

    Rie Y. Umetsu

    2014-12-01

    Full Text Available In order to investigate behavior of magnetic field-induced reverse martensitic transformation for Ni-Co-Mn-Sb, magnetization experiments up to a static magnetic field of 18 T and a pulsed magnetic field of 40 T were carried out. In the thermomagnetization curves for Ni41Co9Mn39Sb11 alloy, the equilibrium transformation temperature T0 was observed to decrease with increasing applied magnetic field, μ0H, at a rate of dT0/dμ0H = 4.6 K/T. The estimated value of entropy change evaluated from the Clausius-Clapeyron relation was about 14.1 J/(K·kg, which was in good agreement with the value obtained by differential scanning calorimetric measurements. For the isothermal magnetization curves, metamagnetic behavior associated with the magnetic field-induced martensitic transformation was observed. The equilibrium magnetic field, μ0H0 = (μ0HAf + μ0HMs/2, of the martensitic transformation tended to be saturated at lower temperature; that is, transformation arrest phenomenon was confirmed for the Ni-Co-Mn-Sb system, analogous with the Ni(Co-Mn-Z (Z = In, Sn, Ga, Al alloys. Temperature dependence of the magnetic field hysteresis, μ0Hhys = μ0HAf − μ0HMs, was analyzed based on the model for the plastic deformation introduced by the dislocations. The behavior can be explained by the model and the difference of the sweeping rate of the applied magnetic field was well reflected by the experimental results.

  18. Sustained activation of DNA damage response in irradiated apoptosis-resistant cells induces reversible senescence associated with mTOR downregulation and expression of stem cell markers.

    Science.gov (United States)

    Chitikova, Zhanna V; Gordeev, Serguei A; Bykova, Tatiana V; Zubova, Svetlana G; Pospelov, Valery A; Pospelova, Tatiana V

    2014-01-01

    Cells respond to genotoxic stress by activating the DNA damage response (DDR). When injury is severe or irreparable, cells induce apoptosis or cellular senescence to prevent transmission of the lesions to the daughter cells upon cell division. Resistance to apoptosis is a hallmark of cancer that challenges the efficacy of cancer therapy. In this work, the effects of ionizing radiation on apoptosis-resistant E1A + E1B transformed cells were investigated to ascertain whether the activation of cellular senescence could provide an alternative tumor suppressor mechanism. We show that irradiated cells arrest cell cycle at G 2/M phase and resume DNA replication in the absence of cell division followed by formation of giant polyploid cells. Permanent activation of DDR signaling due to impaired DNA repair results in the induction of cellular senescence in E1A + E1B cells. However, irradiated cells bypass senescence and restore the population by dividing cells, which have near normal size and ploidy and do not express senescence markers. Reversion of senescence and appearance of proliferating cells were associated with downregulation of mTOR, activation of autophagy, mitigation of DDR signaling, and expression of stem cell markers.

  19. Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

    Directory of Open Access Journals (Sweden)

    Alessandra Menon

    2018-01-01

    Full Text Available Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21% has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF, the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

  20. Sliding-induced non-uniform pre-tension governs robust and reversible adhesion: a revisit of adhesion mechanisms of geckos.

    Science.gov (United States)

    Cheng, Q H; Chen, B; Gao, H J; Zhang, Y W

    2012-02-07

    Several mechanisms have been proposed in the literature to explain the robust attachment and rapid, controllable detachment of geckos' feet on vertical walls or ceilings, yet, it is still debatable, which one is ultimately responsible for geckos' extraordinary capabilities for robust and reversible adhesion. In this paper, we re-examine some of the key movements of geckos' spatula pads and seta hairs during attachment and detachment, and propose a sequence of simple mechanical steps that would lead to the extraordinary properties of geckos observed in experiments. The central subject under study here is a linear distribution of pre-tension along the spatula pad induced by its sliding motion with respect to a surface. The resulting pre-tension, together with a control of setae's pulling force and angle, not only allows for robust and strong attachment, but also enables rapid and controllable detachment. We perform computational modelling and simulations to validate the following key steps of geckos' adhesion: (i) creation of a linear distribution of pre-tension in spatula through sliding, (ii) operation of an instability envelope controlled by setae's pulling force and angle, (iii) triggering of an adhesion instability leading to partial decohesion along the interface, and (iv) complete detachment of spatula through post-instability peeling. The present work not only reveals novel insights into the adhesion mechanism of geckos, but also develops a powerful numerical simulation approach as well as additional guidelines for bioinspired materials and devices.

  1. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria.

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    Full Text Available Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry and culturability (via most-probable number analysis and plating of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.

  2. Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability.

    Science.gov (United States)

    Stöckel, Tino; Summers, Jeffery J; Hinder, Mark R

    2015-01-01

    Intermittent theta burst stimulation (iTBS) has the potential to enhance corticospinal excitability (CSE) and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group) or the vertex (SHAM group). Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.

  3. Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability

    Directory of Open Access Journals (Sweden)

    Tino Stöckel

    2015-01-01

    Full Text Available Intermittent theta burst stimulation (iTBS has the potential to enhance corticospinal excitability (CSE and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group or the vertex (SHAM group. Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.

  4. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

    Directory of Open Access Journals (Sweden)

    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  5. Androgen induces gonadal soma-derived factor, Gsdf, in XX gonads correlated to sex-reversal but not Dmrt1 directly, in the teleost fish, northern medaka (Oryzias sakaizumii).

    Science.gov (United States)

    Horie, Yoshifumi; Myosho, Taijun; Sato, Tadashi; Sakaizumi, Mitsuru; Hamaguchi, Satoshi; Kobayashi, Tohru

    2016-11-15

    In the inbred HNI-II strain of Oryzias sakaizumii, Dmy and Gsdf are expressed in XY gonads from Stages 35 and 36, respectively, similarly to the inbred Hd-rR strain of Oryzias latipes. However, Dmrt1 respectively becomes detectable at Stage 36 and 5 days post hatching (dph) in the two strains. In XX HNI-II embryos, 17α-methyltestosterone (MT) induces Gsdf mRNA from Stage 36, accompanied by complete sex-reversal in all treated individuals (MT, 10 ng/mL), while Dmrt1 mRNA was first detectable at 5 dph. In XX d-rR, MT induced Gsdf mRNA expression and sex-reversal in only some of the treated individuals. Together, these results suggest the testis differentiation cascade in XY individuals differs between the HNI-II and Hd-rR strains. In addition, it is suggested that androgen-induced XX sex-reversal proceeds via an androgen-Gsdf-Dmrt1 cascade and that Gsdf plays an important role in sex-reversal in medaka. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Blood meal induced regulation of the chemosensory gene repertoire in the southern house mosquito

    NARCIS (Netherlands)

    Taparia, Tanvi; Ignell, Rickard; Hill, Sharon Rose

    2017-01-01

    Background: The southern house mosquito, Culex quinquefasciatus, is one of the most prevalent vectors of lymphatic filariasis and flavivirus-induced encephalitis. Its vectorial capacity is directly affected by its reproductive feeding behaviors, such as host seeking, blood feeding, resting, and

  7. Reversible oxidation state change in germanium(tetraphenylporphyrin) induced by a dative ligand: aromatic GeII(TPP) and antiaromatic GeIV(TPP)(pyridine)2.

    Science.gov (United States)

    Cissell, Julie A; Vaid, Thomas P; Yap, Glenn P A

    2007-06-27

    Treatment of GeCl2(dioxane) with Li2(TPP)(OEt2)2 (TPP = tetraphenylporphyrin) in THF yields Ge(TPP), the first free Ge(II) porphyrin complex. In pyridine Ge(TPP) is converted to Ge(TPP)(py)2, an antiaromatic Ge(IV) complex, whereas in benzene the reaction is reversed, and pyridine dissociates from Ge(TPP)(py)2 to form Ge(TPP). That reversible reaction represents an unusual, if not unique, example of an oxidation-state change in a metal induced by coordination of a dative ligand. UV-vis and 1H NMR spectroscopy show that Ge(TPP) is an aromatic Ge(II) porphyrin complex, while the 1H NMR spectrum of Ge(TPP)(py)2 clearly indicates the presence of a strong paratropic ring current, characteristic of an antiaromatic compound. Both Ge(TPP) and Ge(TPP)(py)2 have been crystallographically characterized, and the antiaromaticity of Ge(TPP)(py)2 leads to alternating short and long C-C bonds along the 20-carbon periphery of its porphine ring system. Coordination of pyridine to Ge(TPP) greatly increases its reducing ability: the Ge(TPP)0/2+ redox potential is about +0.2 V, while the Ge(TPP)(py)2(0/+) redox potential is -1.24 V (both vs. ferrocene). The equilibrium constant of the reaction Ge(TPP) + 2 py = Ge(TPP)(py)2 in C6D6 is 22 M-2. The germanium complex of the more electron-withdrawing tetrakis[3,5-bis(trifluoromethyl)phenyl]porphyrin, Ge(TArFP), and its pyridine adduct Ge(TArFP)(py)2 were synthesized. The equilibrium constant of the reaction Ge(TArFP) + 2 py = Ge(TArFP)(py)2 in C6F6/C6D6 is 2.3 x 10(4) M-2. Density functional theory calculations are consistent with the experimental observation that M(TPP)(py)2 formation from M(TPP) and pyridine is most favorable for M=Si, borderline for Ge, and unfavorable for Sn.

  8. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  9. Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-α, and IL-6 in the human pulmonary artery.

    Science.gov (United States)

    Hiram, Roddy; Rizcallah, Edmond; Sirois, Chantal; Sirois, Marco; Morin, Caroline; Fortin, Samuel; Rousseau, Eric

    2014-12-01

    Pulmonary hypertension (PH) is a rare and progressive disease characterized by an inflammatory status and vessel wall remodeling, resulting in increased pulmonary artery resistance. During the last decade, treatments have been proposed; most of them target the endothelial pathways that stimulate smooth muscle cell relaxation. However, PH remains associated with significant morbidity. We hypothesized that inflammation plays a crucial role in the severity of the abnormal vasoconstriction in PH. The goal of this study was to assess the effects of resolvin D1 (RvD1), a potent anti-inflammatory agent, on the pharmacological reactivity of human pulmonary arteries (HPAs) via an in vitro model of induced hyperreactivity. The effects of RvD1 and monoacylglyceride compounds were measured on contractile activity and Ca(2+) sensitivity developed by HPAs that had been pretreated (or not) under proinflammatory conditions with either 10 ng/ml TNF-α or 10 ng/ml IL-6 or under hyperreactive conditions with 5 nM endothelin-1. The results demonstrated that, compared with controls, 24-h pretreatment with TNF-α, IL-6, or endothelin-1 increased reactivity and Ca(2+) sensitivity of HPAs as revealed by agonist challenges with 80 mM KCl, 1 μM serotonin (5-hydroxytryptamine), 30 nM U-46619, and 1 μM phorbol 12,13-dibutyrate. However, 300 nM RvD1 as well as 1 μM monoacylglyceride-docosapentaenoic acid monoglyceride strongly reversed the overresponsiveness induced by both proinflammatory and hyperreactive treatments. In pretreated pulmonary artery smooth muscle cells, Western blot analyses revealed that RvD1 treatment decreased the phosphorylation level of CPI-17 and expression of transmembrane protein member 16A while increasing the detection of G protein-coupled receptor 32. The present data demonstrate that RvD1, a trihydroxylated docosahexaenoic acid derivative, decreases induced overreactivity in HPAs via a reduction in CPI-17 phosphorylation and transmembrane protein member 16A

  10. Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease

    Directory of Open Access Journals (Sweden)

    Smeulders Liesbeth

    2010-10-01

    Full Text Available Abstract Background Current antiretroviral therapy against human immunodeficiency virus (HIV-1 reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection. Here we sought to exploit HIV protease (PR related cytotoxicity in order to develop a strategy for drug induced killing of HIV producing cells. PR processes the viral Gag and Gag-Pol polyproteins during virus maturation, but is also implicated in killing of virus producing cells through off-target cleavage of host proteins. It has been observed previously that micromolar concentrations of certain non-nucleoside reverse transcriptase inhibitors (NNRTIs can stimulate intracellular PR activity, presumably by enhancing Gag-Pol dimerization. Results Using a newly developed cell-based assay we compared the degree of PR activation displayed by various NNRTIs. We identified inhibitors showing higher potency with respect to PR activation than previously described for NNRTIs, with the most potent compounds resulting in ~2-fold increase of the Gag processing signal at 250 nM. The degree of enhancement of intracellular Gag processing correlated with the compound's ability to enhance RT dimerization in a mammalian two-hybrid assay. Compounds were analyzed for their potential to mediate specific killing of chronically infected MT-4 cells. Levels of cytotoxicity on HIV infected cells determined for the different NNRTIs corresponded to the relative degree of drug induced intracellular PR activation, with CC50 values ranging from ~0.3 μM to above the tested concentration range (10 μM. Specific cytotoxicity was reverted by addition

  11. Sorption-induced reversible oxidation of Fe(2) at the smectite/water interface under strictly anoxic conditions. A Moessbauer spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Gehin, A.; Charlet, L. [Laboratoire de Geophysique Interne et Tectonophysique (LGIT), Universite de Grenoble, 38 - Grenoble (France); Gehin, A. [Agence Nationale pour la Gestion des Dechets Radioactifs, ANDRA, 92 - Chatenay Malabry (France); Greneche, J.M. [Laboratoire de Physique de l' Etat Condense, UMR-CNRS 6087, 72 - Le Mans (France); Brendle, J. [Universite de Haute Alsace, Lab. des Materiaux Mineraux (LMM), 68 - Mulhouse (France); Rancourt, D.G. [Ottawa Univ., Dept. of Physics, Ontario (Canada)

    2005-07-01

    not been polymerized, but is present as cations. This result shows that sorption at the clay-water interface occurs in a two steps mechanism: sorption of individual Fe(II) cations, followed by an oxidation of some of them. As a first hypothesis, water could be the oxidizing agent. However in this case, the reversibility of the phenomenon cannot be explained. Thus we proposed, as a second hypothesis, that as pH is increased, protons H{sup +} is removed from the clay surface and, more and more of highly reactive sites acquire steric properties that stabilize Fe(III) relative to Fe(II). This differential affinity induces in turn an Fe-to-clay particle electron transfer. The change in surface site local environment is shown by observed large pH induced change in the sorbed Fe(II) quadrupole splitting distributions. (authors)

  12. Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-α/IFN-γ-induced inflammatory response in keratinocytes and T cell-derived IL-17.

    Science.gov (United States)

    Lin, Ze-Min; Ma, Meng; Li, Heng; Qi, Qing; Liu, Yu-Ting; Yan, Yu-Xi; Shen, Yun-Fu; Yang, Xiao-Qian; Zhu, Feng-Hua; He, Shi-Jun; Tang, Wei; Zuo, Jian-Ping

    2018-03-01

    DZ2002, a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. The present study was designed to characterize the potential therapeutic effects of DZ2002 on murine model of psoriasis and reveal the correlated mechanisms. In this report, we demonstrated that in vitro, DZ2002 significantly decreased the expression of pro-inflammatory cytokines and adhesion molecule including IL-1α, IL-1β, IL-6, IL-8, TNF-α and ICAM-1 by inhibiting the phosphorylation of p38 MAPK, ERK and JNK in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes. Topical administration of DZ2002 alleviated the imiquimod (IMQ)-induced psoriasis-like skin lesions and inflammation in mice, the therapeutic effect was comparable with the Calcipotriol. Moreover, the inflammatory skin disorder was restored by DZ2002 treatment characterized by reducing both of the CD3 + T cell accumulation and the psoriasis-specific cytokines expression. Further, we found that DZ2002 improved IMQ-induced splenomegaly and decreased the frequency of splenic IL-17-producing T cells. Our finding offered the convincing evidence that SAHH inhibitor DZ2002 might attenuate psoriasis by simultaneously interfering the abnormal activation and differentiation of keratinocytes and accumulation of IL-17-producing T cells in skin lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Ginsenoside Rg1 reverses stress-induced depression-like behaviours and brain-derived neurotrophic factor expression within the prefrontal cortex.

    Science.gov (United States)

    Zhu, Xiuzhi; Gao, Rui; Liu, Zhuxi; Cheng, Ziyi; Qi, Yihang; Fan, Cuiqin; Yu, Shu Yan

    2016-07-01

    Depression is a major neuropsychiatric disorder that exerts deleterious effects upon public health. However, the neuronal mechanisms of depression remain largely uncharacterized, which has retarded the identification and development of effective therapeutic tools for the treatment of this disorder. The aim of this study was to explore the neuronal mechanisms underlying the protective effects of ginsenoside Rg1, a natural steroidal saponin found in ginseng, against chronic stress-induced depression.The results showed that chronic administration of ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) significantly ameliorated depression-like behaviours in rats as assessed in the sucrose preference and forced swim tests. Furthermore, chronic stress decreased the phosphorylation levels of the extracellular signal-regulated kinase and cAMP-response element-binding protein in the prefrontal cortex as well as producing a reduction of brain-derived neurotrophic factor expression. Of particular importance, all reductions in these parameters were significantly reversed by pre-treatment with ginsenoside Rg1. Taken together, the results of the present study suggest that the antidepressant-like effect of ginsenoside Rg1 might be mediated, at least in part, by activating the cAMP-response element-binding protein-brain-derived neurotrophic factor system within the prefrontal cortex. These findings not only reveal some of the underlying neuronal mechanisms of depression, but also the therapeutic potential of ginsenoside Rg1 as a preventive agent in the treatment of depression. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring.

    Science.gov (United States)

    Xue, Baojian; Yin, Haifeng; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim

    2017-04-01

    Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. © 2017 American Heart Association, Inc.

  15. Risk factors and the choice of long-acting reversible contraception following medical abortion: effect on subsequent induced abortion and unwanted pregnancy.

    Science.gov (United States)

    Korjamo, Riina; Heikinheimo, Oskari; Mentula, Maarit

    2018-04-01

    To analyse the post-abortion effect of long-acting reversible