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Sample records for cisplatin-induced heat hyperalgesia

  1. Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

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    Carlton Susan M

    2010-03-01

    Full Text Available Abstract Background Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR, we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.

  2. Secondary hyperalgesia to heat stimuli after burn injury in man

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    Pedersen, J L; Kehlet, H

    1998-01-01

    The aim of the study was to examine the presence of hyperalgesia to heat stimuli within the zone of secondary hyperalgesia to punctate mechanical stimuli. A burn was produced on the medial part of the non-dominant crus in 15 healthy volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min), and...... assessments were made 70 min and 40 min before, and 0, 1, and 2 h after the burn injury. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain responses were rated with a visual analog scale (0-100). The area of secondary hyperalgesia...... to punctate stimuli was assessed with a rigid von Frey hair (462 mN). The heat pain responses to 45 degrees C in 5 s (3.75 cm2) were tested in the area just outside the burn, where the subjects developed secondary hyperalgesia, and on the lateral crus where no subject developed secondary hyperalgesia...

  3. Cisplatin Induced Nephrotoxicity

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    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  4. Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization?

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    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen;

    2016-01-01

    investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important...... role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the......) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an...

  5. Aberrant TRPV1 Expression in Heat Hyperalgesia Associated with Trigeminal Neuropathic Pain

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    Hiroko Urano, Toshiaki Ara, Yoshiaki Fujinami, B. Yukihiro Hiraoka

    2012-01-01

    Full Text Available Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1 in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

  6. Cisplatin-Induced Eosinophilic Pneumonia

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    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  7. The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility.

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    Morten Sejer Hansen

    Full Text Available Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min in healthy volunteers.Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min., and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied.For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006.We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers.clinicaltrials.gov NCT02166164.

  8. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers

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    Jensen, Magnus Thorsten; Petersen, Karin Lottrup

    2006-01-01

    /capsaicin sensitization, and heat pain detection thresholds. There was a trend toward smaller areas of secondary hyperalgesia in women. After adjusting for estimated gender differences in forearm surface area, areas to brush but not von Frey hair stimulation after capsaicin sensitization were larger in women. Peak pain......, but not total pain, during prolonged noxious thermal stimulation was higher in women. There was no gender difference in pain ratings during capsaicin sensitization or in heat pain detection thresholds. The results provided only limited support to the hypothesis that gender differences in clinical pain...... syndromes can be explained by enhanced central sensitization in women. PERSPECTIVE: Our findings suggest that gender differences in nociceptive transmission and neuronal sensitization are small and provide only limited support to the hypothesis that gender differences in acute and chronic pain syndromes can...

  9. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons

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    2014-01-01

    Background Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. Methods CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). Results The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia

  10. GERANYLGERANYLACETONE ATTENUATES CISPLATIN-INDUCED REDUCTIONS IN CELL VIABILITY BY SUPPRESSING THE ELEVATION OF INTRACELLULAR P53 CONTENT WITHOUT HEAT SHOCK PROTEIN INDUCTION

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    HASEGAWA, MOTOFUSA; ISHIGURO, KAZUHIRO; ANDO, TAKAFUMI; GOTO, HIDEMI

    2012-01-01

    ABSTRACT Geranylgeranylacetone (GGA) was originally used as an anti-ulcer drug to protect gastric mucosa from various stresses, and it is also known to induce heat shock proteins (HSPs), especially HSP70. However, it remains unclear how GGA affects cellular functions in the presence of anti-cancer drugs. We investigated the effects of GGA on cellular viability, caspase-3 activation, HSP induction and p53 content in the presence of cisplatin (CDDP). Rat intestinal epithelium-derived IEC-18 cells and human colon cancer-derived CW-2 cells were incubated with GGA in the presence of CDDP, and we observed that GGA attenuated CDDP-induced viability reductions. GGA also suppressed CDDP-induced caspase-3 activation. However, GGA induced neither HSP70 nor GRP78 expression in the presence of CDDP. We found that GGA suppressed the CDDP-induced elevation of intracellular p53 content. In conclusion, GGA attenuates viability reductions and caspase-3 activation in CDDP-treated cells by suppressing the elevation of intracellular p53 content without HSP induction. PMID:22515118

  11. The effect of pre- versus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin

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    Dahl, J B; Brennum, J; Arendt-Nielsen, L; Jensen, T S; Kehlet, H

    1993-01-01

    observed 100-190 min after injury. Likewise, there was no difference in thermal thresholds inside the injury between pre- and postinjury treatment at the end of the study period. It is concluded, that a shortlasting 'preemptive' infiltration with lidocaine may postpone but not prevent the occurrence of......The aim of the study was to evaluate the effects of pre- and postinjury infiltration with lidocaine on alterations in mechanical and thermal sensitivity after heat injury to the skin. In the first part of the study, burn injuries (15 x 25 mm rectangular thermode, 50 degrees C, 7 min) were produced...... hyperalgesia outside a thermal injury....

  12. Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

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    Ikemoto Tatsunori

    2009-08-01

    Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

  13. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

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    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  14. Cellular Responses to Cisplatin-Induced DNA Damage

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    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  15. Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

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    Kopruszinski, Caroline M; Reis, Renata C; Bressan, Elisangela; Reeh, Peter W; Chichorro, Juliana G

    2015-09-01

    Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects. PMID:26048309

  16. Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity.

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    Athira, K V; Madhana, Rajaram Mohanrao; Lahkar, Mangala

    2016-03-25

    The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-κB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy. PMID:26876905

  17. Cetuximab intensifies cisplatin-induced testicular toxicity.

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    Levi, Mattan; Popovtzer, Aron; Tzabari, Moran; Mizrachi, Aviram; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2016-07-01

    Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Müllerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity. PMID:27184186

  18. Parthenolide reduces cisplatin-induced renal damage

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    Inflammatory events contribute to cisplatin-induced renal damage. Cisplatin promotes increased production of reactive oxygen species, which can activate nuclear factor-κB (NF-κB) that lead to increased expression of proinflammatory mediators which could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect of parthenolide, a selective inhibitor of NF-κB, on renal damage caused by cisplatin use. A total of 94 male Wistar rats were divided into six groups: Group A (18 rats) were treated with saline; Group B (12 rats) received dimethylsulfoxide plus saline (the solvent for parthenolide); Group C (12 rats) received parthenolide (3 mg/kg) plus saline; Group D (20 rats) received cisplatin (5 mg/kg, i.p.); Group E (12 rats) received dimethylsulfoxide plus cisplatin (5 mg/kg, i.p.); and Group F (21 rats) received parthenolide (3 mg/kg) plus cisplatin (5 mg/kg, i.p.). Dimethylsulfoxide or parthenolide were administered at 24 h and 1 h prior to cisplatin injection, and again at 24 h and 48 h after. At 2, 3 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium and the kidneys removed for histological, morphometric, electrophoretic mobility shift assay (EMSA), apoptosis and immunohistochemical studies. Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes) and NF-κB in the renal cortices and outer medullae. The increase of NF-κB activation was confirmed by EMSA. Cisplatin-injected rats also presented higher urinary levels of lipid peroxidation and acute tubular necrosis. All of these alterations were reduced by treatment with parthenolide. This effect seems to be related, at least in part, to the restriction of renal inflammatory process observed in parthenolide + cisplatin treated rats

  19. Mechanisms of cisplatin-induced muscle atrophy

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    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin

  20. Mechanisms of cisplatin-induced muscle atrophy

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    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  1. Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers

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    Koerber H Richard

    2010-09-01

    Full Text Available Abstract Background Previous studies have shown that the TRPV1 ion channel plays a critical role in the development of heat hyperalgesia after inflammation, as inflamed TRPV1-/- mice develop mechanical allodynia but fail to develop thermal hyperalgesia. In order to further investigate the role of TRPV1, we have used an ex vivo skin/nerve/DRG preparation to examine the effects of CFA-induced-inflammation on the response properties of TRPV1-positive and TRPV1-negative cutaneous nociceptors. Results In wildtype mice we found that polymodal C-fibers (CPMs lacking TRPV1 were sensitized to heat within a day after CFA injection. This sensitization included both a drop in average heat threshold and an increase in firing rate to a heat ramp applied to the skin. No changes were observed in the mechanical response properties of these cells. Conversely, TRPV1-positive mechanically insensitive, heat sensitive fibers (CHs were not sensitized following inflammation. However, results suggested that some of these fibers may have gained mechanical sensitivity and that some previous silent fibers gained heat sensitivity. In mice lacking TRPV1, inflammation only decreased heat threshold of CPMs but did not sensitize their responses to the heat ramp. No CH-fibers could be identified in naïve nor inflamed TRPV1-/- mice. Conclusions Results obtained here suggest that increased heat sensitivity in TRPV1-negative CPM fibers alone following inflammation is insufficient for the induction of heat hyperalgesia. On the other hand, TRPV1-positive CH fibers appear to play an essential role in this process that may include both afferent and efferent functions.

  2. Protective effect of metalloporphyrins against cisplatin-induced kidney injury in mice.

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    Hao Pan

    Full Text Available Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced nephrotoxicity. The purpose of this work is to study the role of two metalloporphyrins (FeTMPyP and MnTBAP, water soluble complexes, in cisplatin-induced renal damage and their ability to scavenge peroxynitrite. In cisplatin-induced nephropathy study in mice, renal nitrative stress was evident by the increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident by the histological damage from the loss of the proximal tubular brush border, blebbing of apical membranes, tubular epithelial cell detachment from the basement membrane, or intra-luminal aggregation of cells and proteins and by the increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity were attenuated by both metalloporphyrins. Heme oxygenase (HO-1 also plays a critical role in metalloporphyrin-mediated protection of cisplatin-induced nephrotoxicity. It is evident that nitrative stress plays a critical role in cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration and cisplatin-induced nephrotoxicity can be prevented with the use of metalloporphyrins.

  3. Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity

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    Lee, Chi-Kyou; Shin, Jang-In; Cho, Yang-Sun

    2011-01-01

    Objectives Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in v...

  4. C-phycocyanin attenuates cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Lim, Beom Jin; Jeong, Jin Young; Chang, Yoon-Kyung; Na, Ki-Ryang; Lee, Kang Wook; Shin, Young-Tai; Choi, Dae Eun

    2012-01-01

    Although cisplatin is a highly effective antineoplastic agent, nephrotoxicity is its major clinical problem. Recently, it was reported that Spirulina, a blue-green algae, has potent antioxidant properties. The aim of this study was to establish the possible protective role of C-phycocyanin (PC), one of the active ingredients of Spirulina, against cisplatin-induced nephrotoxicity. This study was carried out using human kidney-2 (HK-2) cells and male C57BL6 mice. Cells and mice were divided into four groups; untreated control group, PC-treated control group, cisplatin-treated group, and PC plus cisplatin-treated group. The molecular, functional, and structural parameters were measured. PC significantly attenuated blood urea nitrogen, serum creatinine, renal histological damages, and apoptotic cell death in cisplatin-treated mice. The cisplatin-induced cell death was significantly attenuated in cells pretreated with PC. PC also significantly attenuated the elevation of p-ERK, p-JNK, and p-p38 induced by cisplatin treatment. The expression of Bax, caspase-9, and caspase-3 in cisplatin-treated cells were also decreased by PC treatment. In conclusion, PC ameliorates cisplatin-induced nephrotoxicity and, at least in part, suppression of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 may be involved in this mechanism. PMID:22681485

  5. EFFECT OF ANTHOCYANIN FRACTION ON CISPLATIN-INDUCED NEPHROTOXICITY

    OpenAIRE

    Adikay Sreedevi; Belide Pavani

    2012-01-01

    Present study was designed to evaluate the effect of anthocyanin fraction of Syzygium cumini on cisplatin-induced nephrotoxicity in male Albino rats. Anthocyanin fraction was administered by gastric intubation at two dose levels. Animals were divided into 5 groups. Group I animals received vehicle. On day 1, Group II animals received cisplatin (6 mg/kg, i,p., single dose). Group III (7.5mg/kg) and IV (15mg/kg) received anthocyanin fraction respectively at 1 hr before, 24 hr and 48 hr after ci...

  6. Walnut consumption protects rats against cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Shabani, Mohammad; Nazeri, Masoud; Parsania, Shahrnaz; Razavinasab, Moazamehosadat; Zangiabadi, Nasser; Esmaeilpour, Khadije; Abareghi, Fatemeh

    2012-10-01

    Walnut is extensively used in traditional medicine for treatment of various ailments. It is described as an anticancer, anti-inflammatory, blood purifier and antioxidant agent. In this study, we investigated whether or not Walnut could protect neurons against cisplatin-induced neurotoxicity in rats. Dietary walnut (6%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin treatment (5 mg/kg/week for 5 consecutive weeks) in male rats. We also evaluated the effect of cisplatin and walnut administration on nociception. We showed that exposure of adolescent rats to cisplatin resulted in significant decrease in explorative behaviors and memory retention. Walnut consumption improved memory and motor abilities in cisplatin treated rats, while walnut alone did not show any significant changes in these abilities compared to saline. Cisplatin increased latency of response to nociception, and walnut reversed this effect of cisplatin. We conclude that walnuts in the diet following anticancer drugs such as cisplatin might have a protective effect against cisplatin-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of walnut and to explore underlying mechanisms. PMID:22935099

  7. Electroacupuncture alleviates cisplatin-induced nausea in rats

    Science.gov (United States)

    Cui, Yingxue; Wang, Linpeng; Shi, Guangxia; Liu, Lu; Pei, Pei; Guo, Jianyou

    2016-01-01

    Objective Acupuncture has been shown to be effective for the treatment of chemotherapy-related nausea and vomiting. The aim of this study was to explore the mechanisms of action underlying the anti-emetic effect of electroacupuncture (EA). Design Forty-eight rats received saline (n=12) or 6 mg/kg cisplatin (n=36) to establish a chemotherapy-induced nausea and vomiting model. EA was performed at CV12 (n=12), bilateral PC6 (n=12), or sham points (n=12) 3 days before and 1–2 days after cisplatin administration (4–5 times in total), at 0.5–1 mA intensity and 2/15 Hz frequency for 10 min. Kaolin intake, food intake and bodyweight change were evaluated as markers of nausea and vomiting severity. Concentrations of serotonin (5-hydroxytryptamine, 5-HT) in the duodenum and c-Fos expression in the nucleus of the solitary tract (NTS) were measured using high performance liquid chromatography and immunohistochemistry, respectively. Results Cisplatin administration led to increased kaolin intake and reduced food intake and bodyweight over the following 2 days. EA at CV12 significantly reversed the cisplatin-induced change in kaolin intake (on days 1 and 2) and food intake and bodyweight (on day 1). EA at CV12 also attenuated the cisplatin-induced increase in 5-HT in the duodenum and suppressed c-Fos expression in the NTS. EA at PC6 influenced kaolin intake (on day 1 only) and c-Fos expression, but had no statistically significant effect on food intake, bodyweight or 5-HT expression. Conclusions This study demonstrated beneficial effects of EA on chemotherapy-induced nausea and vomiting in a rat model. The anti-emetic effect of EA may be mediated through inhibition of 5-HT secretion in the duodenum and activity of the NTS. PMID:26386034

  8. Infrasound sensitizes human glioblastoma cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Rachlin, Kenneth; Moore, Dan H; Yount, Garret

    2013-11-01

    The development of nontoxic agents that can selectively enhance the cytotoxicity of chemotherapy is an important aim in oncology. This study evaluates the ability of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced apoptosis. The infrasound was delivered using a device designed to replicate the unique infrasound emissions measured during external Qigong treatments. Human glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210, and SF188) were treated in culture with cisplatin, infrasound emissions, or the combination of the 2 agents. Induction of apoptosis was quantified after 24 hours by flow cytometry following annexin V/propidium iodide staining. Infrasound emissions alone, delivered at moderate levels (~10 mPa) with dynamic frequency content (7-13 Hz), did not induce apoptosis, yet combining infrasound with cisplatin augmented the induction of apoptosis by cisplatin in all the 4 cell lines (P infrasound exposure was quantified by fluorescence microscopy as well as flow cytometry, demonstrating increased cell membrane permeability. The 4 cell lines differed in the degree to which infrasound exposure increased calcein uptake, and these differences were predictive of the extent to which infrasound enhanced cisplatin-induced apoptosis. When exposed to specific frequencies, membrane permeabilization also appeared to be differentially responsive for each cell line, suggesting the potential for selective targeting of tissue types using isolated infrasonic frequencies. Additionally, the pressure amplitudes used in this study were several orders of magnitude less than those used in similar studies involving ultrasound and shock waves. The results of this study provide support for using infrasound to enhance the chemotherapeutic effects of cisplatin in a clinical setting. PMID:23165942

  9. Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Chen, Cheng-Lung; Liao, Jiunn-Wang; Hu, Oliver Yoa-Pu; Pao, Li-Heng

    2016-09-01

    Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function loss, renal tubular damage, and the induction of the apoptotic marker caspase-3 in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice. Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated cytochrome c release and the increase in the intrinsic apoptotic mediators Bax, Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator caspase-12, which is independent of calcium-dependent protease m-calpain activation. Taken together, KCa3.1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI. PMID:26438401

  10. Nebivolol Ameliorates Cisplatin-Induced Nephrotoxicity in Rats.

    Science.gov (United States)

    Morsy, Mohamed A; Heeba, Gehan H

    2016-06-01

    Treatment with cisplatin is associated with dose-limiting side effects, mainly nephrotoxicity. On the other hand, nebivolol, a β1 -adrenoceptor antagonist, exhibits vasodilatory and antioxidative properties. This study aimed to determine whether nebivolol possesses a protective effect against cisplatin nephrotoxicity and explore many mechanisms underlying this potential effect. Nephrotoxicity was induced in Wistar rats by a single intraperitoneal injection of cisplatin (6 mg/kg) on day 2. Nebivolol (10 mg/kg) was administered orally for 7 consecutive days. Nebivolol showed a nephroprotective effect as demonstrated by the significant reduction in the elevated levels of serum creatinine and urea as well as renal levels of malondialdehyde, nitric oxide products (nitrite/nitrate), inducible nitric oxide synthase, tumour necrosis factor-alpha, caspase-3, angiotensin II and endothelin-1 with a concurrent increase in renal levels of reduced glutathione and endothelial nitric oxide synthase compared to untreated rats. Histopathological examination confirmed the nephroprotective effect of nebivolol. Pre-treatment with Nω -nitro-L-arginine methyl ester, the non-specific nitric oxide synthase inhibitor, partially altered the protection afforded by nebivolol. In conclusion, nebivolol protects rats against cisplatin-induced nephrotoxicity that is most likely through its antioxidant, anti-inflammatory and antiapoptotic effects as well as by abrogation of the augmented angiotensin II and endothelin-1 levels. PMID:26617394

  11. Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model

    OpenAIRE

    Campbell, Claudia M.; Bounds, Sara C.; Simango, Mpepera B.; Witmer, Kenneth R.; Campbell, James N.; Edwards, Robert R.; Haythornthwaite, Jennifer A; Smith, Michael T.

    2010-01-01

    Although sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep-pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction. We utilized the heat-capsaicin nociceptive model to examine whether self-rep...

  12. TRPV1 Receptor in Expression of Opioid-induced hyperalgesia

    OpenAIRE

    Vardanyan, Anna; Wang, Ruizhong; Vanderah, Todd W.; Ossipov, Michael H.; Lai, Josephine; Porreca, Frank; King, Tamara

    2008-01-01

    Opiates are currently the mainstay for treatment of moderate to severe pain. However, prolonged administration of opiates has been reported to elicit hyperalgesia in animals and examples of opiate-induced hyperalgesia have been reported in humans as well. In spite of the potential clinical significance of such opiate-induced actions, the mechanisms of opiate-induced hypersensitivity remain unknown. The TRPV1 receptor, a molecular sensor of noxious heat, acts as an integrator of multiple forms...

  13. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats

    OpenAIRE

    Ko, Je-Won; Lee, In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-01-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological al...

  14. Mapping the Binding Site of TRPV1 on AKAP79: Implications for Inflammatory Hyperalgesia

    OpenAIRE

    Btesh, Joan; Fischer, Michael J. M.; Stott, Katherine; McNaughton, Peter A.

    2013-01-01

    Inflammation causes hyperalgesia, an enhanced sensitivity to noxious stimuli. Transient receptor potential vanilloid 1 (TRPV1), a thermo-TRP ion channel activated by painful levels of heat, is an important contributor because hyperalgesia is reduced when TRPV1 is either genetically deleted or pharmacologically blocked. Inflammatory mediators such as prostaglandin-E2 or bradykinin cause hyperalgesia by activating cellular kinases that phosphorylate TRPV1, a process that has recently been shown...

  15. The sythetic endomorphin-1 analog, CYT-1010, inhibits sensory neuropeptide release, acute neurogenic inflammation and heat injury-induced thermal hyperalgesia in rodent models

    OpenAIRE

    Z. Helyes; J. Szolcsanyi; T. Maione

    2011-01-01

    Calcitonin gene-related peptide (CGRP) and substance P released from capsaicin-sensitive afferents induce neurogenic inflammatory and nociceptive actions. Since we have shown that the m opioid receptor agonist endomorphin-1 inhibits sensory neuropeptide outflow, the effects of its synthetic, peptidase-resistant analog, CYT-1010, was studied on CGRP release, acute neurogenic inflammation and thermal hyperalgesia. CGRP release from sensory fibres of isolated rat tracheae was evoked by electrica...

  16. Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup; Holm, Jacob Bak; Poulsen, Kristian Arild;

    2010-01-01

    have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of glutathione and taurine has no effect on cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the taurine transporter TauT leads to a...

  17. Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity.

    Science.gov (United States)

    Dugbartey, George J; Bouma, Hjalmar R; Lobb, Ian; Sener, Alp

    2016-07-01

    Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury. PMID:27095538

  18. Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats.

    Science.gov (United States)

    Jamshidzadeh, Akram; Heidari, Reza; Golzar, Tahereh; Derakhshanfar, Amin

    2016-09-01

    Kidney injury is a deleterious side effect accompanied by therapeutic uses of cisplatin as an antineoplastic agent. However, no therapeutic option is available against this complication. This study was designed to evaluate the protective role of a glycoprotein extract obtained from Eisenia foetida against cisplatin-induced nephrotoxicity. Rats were treated with cisplatin (7.5 mg/kg, intraperitoneally, i.p.) and Eisenia foetida extract (300 and 500 mg/kg, i.p. and/or oral). Serum creatinine (Cr) and blood urea nitrogen (BUN) were significantly elevated in cisplatin-treated rats. A significant amount of lipid peroxidation was detected in drug-treated animals. Furthermore, kidney histopathological findings revealed acute tubular necrosis and hyaline cast formation caused by cisplatin. Eisenia foetida extract administration (300 and 500 mg/kg, i.p.) significantly reduced serum BUN and creatinine and lipid peroxidation in kidney tissue. Moreover, cisplatin-induced histopathological lesions were alleviated by Eisenia foetida extract. This investigation concluded that Eisenia foetida extract ameliorated cisplatin-induced nephrotoxicity. This protection might be mediated by preventing cisplatin-induced oxidative stress. PMID:26864051

  19. Fear of pain potentiates nocebo hyperalgesia

    Directory of Open Access Journals (Sweden)

    Aslaksen PM

    2015-10-01

    Full Text Available Per M Aslaksen,1 Peter S Lyby2 1Department of Psychology, Research Group for Cognitive Neuroscience, The Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; 2Catosenteret Rehabilitation Center, Son, Norway Abstract: Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia. One hundred and eleven healthy volunteers (76 females participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain. Personality traits were measured by the Big-Five Inventory-10. Fear of pain was measured by the Fear of Pain Questionnaire III. Heat pain was induced by a PC-controlled thermode. Pain was measured by a computerized visual analog scale. Stress levels during the experiment were measured by numerical rating scales. The participants were randomized to a Nocebo group or to a no-treatment Natural History group. The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment. Mediation analysis showed that higher levels of the Fear of Pain Questionnaire III factor "fear of medical pain" significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses. There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect. The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain. Furthermore, measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality

  20. Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress.

    Science.gov (United States)

    Trujillo, Joyce; Molina-Jijón, Eduardo; Medina-Campos, Omar Noel; Rodríguez-Muñoz, Rafael; Reyes, José Luis; Loredo, María L; Barrera-Oviedo, Diana; Pinzón, Enrique; Rodríguez-Rangel, Daniela Saraí; Pedraza-Chaverri, José

    2016-01-20

    Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor β1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C β2, and Nrf2) as well as by decreased expression of occludin, claudin-2, β-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity. PMID:26467482

  1. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale).

    Science.gov (United States)

    Sharma, S S; Gupta, Y K

    1998-08-01

    Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100, 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT3 receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy. PMID:9720611

  2. Decursin Mediated Protection on Cisplatin-induced Nephrotoxicity in SD Rats and BDF1 Mice

    Institute of Scientific and Technical Information of China (English)

    Jiang Cheng-zhe; Han Ilhyun; Choung Seyoung

    2012-01-01

    Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.

  3. Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing FAN; Yun-wei OU; Chuan-yue WU; Chun-jiang YU; Yong-mei SONG; Qi-min ZHAN

    2012-01-01

    Aim:Filamin binding LIM protein 1,also known as migfilin,is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions.The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells,to determine the functional domains of migfilin,and to elucidate the molecular mechanisms underlying the regulation of cisplatin-related chemosensitivity.Methods:The human glioma cell lines Hs683,H4,and U-87 MG were transfected with pEGFP-C2-migfilin to elevate the expression level of migfilin.RNA interference was used to reduce the expression of migfilin.To determine the functional domains of migfilin,U-87 MG cells were transfected with plasmids of migfilin deletion mutants.After treatment with cisplatin (40 μmol/L) for 24 h,the cell viability was assessed using the MTS assay,and the cell apoptotic was examined using the DAPI staining assay and TUNEL analysis.Expression levels of apoptosis-related proteins were detected by Western blot analysis.Results:Overexpression of migfilin significantly enhanced cisplatin-induced apoptosis in Hs683,H4,and U-87 MG cells,whereas downregulation of migfilin expression inhibited the chemosensitivity of these cell lines.The N-terminal region of migfilin alone was able to enhance the cisplatin-induced apoptosis.However,despite the existence of the N-terminal region,mutants of migfilin with any one of three LIM domains deleted led to a function loss.Furthermore,apoptotic proteins (PARP and caspase-3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level of migfilin in combination with cisplatin.Conclusion:The LIM1-3 domains of migfilin play a key role in sensitizing glioma cells to cisplatin-induced apoptosis through regulation of apoptosis-related proteins.

  4. Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

    OpenAIRE

    Smyth, J. F.; Coleman, R E; Nicolson, M.; Gallmeier, W M; Leonard, R C; Cornbleet, M. A.; Allan, S G; Upadhyaya, B K; Bruntsch, U

    1991-01-01

    OBJECTIVE--To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN--Randomised double blind crossover study. SETTING--Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS--100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS--Patients were g...

  5. Ondansetron compared with ondansetron plus metoclopramide in the prevention of cisplatin-induced emesis.

    OpenAIRE

    Lee, C. W.; Suh, C. W.; Lee, J. S.; Lee, K. H.; Cho, G. Y.; Kim, S.W.; Kim, S H

    1994-01-01

    To determine the contribution of metoclopramide to the efficacy of ondansetron in control of cisplatin-induced emesis, ondansetron was compared with ondansetron plus metoclopramide for antiemetic efficacy in a randomized double-blind trial. Enrolled 66 patients were treated with cisplatin(60mg/m2) in combination with etoposide, flourouracil, or vinblastine, and randomized to receive either ondansetron alone or ondansetron plus metoclopramide. Sixty patients were evaluable. Complete or major c...

  6. Evaluating the various phases of cisplatin-induced emesis in rats

    OpenAIRE

    Shi, Jun

    2014-01-01

    Use of cisplatin as a chemotherapeutic agent causes acute and delayed emesis. Kaolin, saccharin solution and normal feed consumption have been evaluated as an index of cisplatin-induced emesis in rats; however, the most preferable of these methods for evaluating the various phases of emesis remains unclear. In the current study, kaolin, saccharin solution and normal feed consumption following cisplatin administration (6 mg/kg intraperitoneally) were simultaneously investigated in rats. Kaolin...

  7. Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

    OpenAIRE

    Ohno T; Yanai M; Ando H; Toyomasu Y; Ogawa A; Morita H; Ogata K; Mochiki E; Asao T; Kuwano H

    2011-01-01

    Tetsuro Ohno, Mitsuhiro Yanai, Hiroyuki Ando, Yoshitaka Toyomasu, Atsushi Ogawa, Hiroki Morita, Kyoichi Ogata, Erito Mochiki, Takayuki Asao, Hiroyuki KuwanoDepartment of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, JapanBackground: The aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans.Methods: The study was performed as a crossover design, and ten unresectable or relapsed gastri...

  8. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ko, Je-Won; Lee, In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-12-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity. PMID:25628728

  9. Vetiver oil (Java) attenuates cisplatin-induced oxidative stress, nephrotoxicity and myelosuppression in Swiss albino mice.

    Science.gov (United States)

    Sinha, Sonali; Jothiramajayam, Manivannan; Ghosh, Manosij; Jana, Aditi; Chatterji, Urmi; Mukherjee, Anita

    2015-07-01

    Clinical efficacy of the widely used anticancer drug cisplatin is limited due to its adverse side effects in normal tissues mediated by oxidative stress. This study was aimed to investigate the protective effects of vetiver acetate oil, Java (VO) against cisplatin-induced toxicity in Swiss albino mice. The ameliorating potential was evaluated by orally priming the animals with VO at doses 5, 10 or 20 mg/kg bw for 7 days prior to cisplatin treatment. Acute toxicity in mice was induced by injecting cisplatin (3 mg/kg bw) intraperitoneally for 5 consecutive days. Significant attenuation of renal toxicity was confirmed by histopathological examination, lowered levels of serum blood urea nitrogen, creatinine and reduced DNA damage. VO also compensated deficits in the renal antioxidant system. VO intervention significantly inhibited DNA damage, clastogenic effects, and cell cycle arrest in the bone marrow cells of mice. Hematological parameters indicated attenuation of cisplatin-induced myelosuppression. Overall, this study provides for the first time that VO has a protective role in the abatement of cisplatin-induced toxicity in mice which may be attributed to its antioxidant activity. PMID:25910835

  10. Fear of pain potentiates nocebo hyperalgesia.

    Science.gov (United States)

    Aslaksen, Per M; Lyby, Peter S

    2015-01-01

    Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia. One hundred and eleven healthy volunteers (76 females) participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain. Personality traits were measured by the Big-Five Inventory-10. Fear of pain was measured by the Fear of Pain Questionnaire III. Heat pain was induced by a PC-controlled thermode. Pain was measured by a computerized visual analog scale. Stress levels during the experiment were measured by numerical rating scales. The participants were randomized to a Nocebo group or to a no-treatment Natural History group. The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment. Mediation analysis showed that higher levels of the Fear of Pain Questionnaire III factor "fear of medical pain" significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses. There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect. The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain. Furthermore, measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality. PMID:26491370

  11. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways.

    Science.gov (United States)

    Thongnuanjan, Penjai; Soodvilai, Sirima; Chatsudthipong, Varanuj; Soodvilai, Sunhapas

    2016-01-01

    Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment. PMID:27193727

  12. Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Kimura, Toru; Tokudome, Takeshi; Miura, Koichi; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

    2016-08-01

    Cisplatin is a potent chemotherapeutic agent that has activity against malignant tumors. However, cisplatin causes various adverse effects, such as nephrotoxicity, which are associated with high morbidity and mortality. Recent studies have revealed that the mechanism of cisplatin nephrotoxicity includes a robust inflammatory response. Since ghrelin has been shown to have anti-inflammatory properties, we hypothesized that ghrelin might have protective effects against cisplatin nephrotoxicity. Mice were randomly divided into three groups: control, cisplatin with vehicle, and cisplatin with ghrelin. Ghrelin (0.8μg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started one day before cisplatin injection. At 72h after cisplatin administration (20mg/kg, intraperitoneally), we measured serum blood urea nitrogen and creatinine, urine albumin/creatinine, renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, interleukin-1β, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin by real-time polymerase chain reaction, and histological changes. Ghrelin significantly attenuated the increase in serum blood urea nitrogen and creatinine induced by cisplatin. Ghrelin tended to attenuate the increase in urine albumin/creatinine, although not significantly. Cisplatin-induced renal tubular injury and apoptosis were significantly attenuated by ghrelin pretreatment. Consequently, ghrelin significantly attenuated renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. In conclusion, ghrelin produces protective effects in cisplatin-induced nephrotoxicity through inhibition of inflammatory reactions. Pretreatment with ghrelin may become a new prophylactic candidate for cisplatin-induced nephrotoxicity. PMID:27298204

  13. The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries

    OpenAIRE

    Durdu Altuner; Mine Gulaboglu; Omer Erkan Yapca; Nihal Cetin

    2013-01-01

    Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After t...

  14. Comment on: A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats

    Directory of Open Access Journals (Sweden)

    Hamid Nasri

    2013-01-01

    Full Text Available Cisplatin (cis-diamminedichloroplatinum II, as one of the most applicable and potent anticancer medication, is used in the treatment of a various pediatric and adult malignancies. However, it gives side-effects such as renal toxicity which is dose-dependent, and thus limited its usage. Treatment with cisplatin induces the inflammatory mechanisms, which leads to a reduction in the antioxidant levels, leading to a failure of the antioxidant protection against free-radical damage generated by antitumor drugs. The oxidative stress, induced by cisplatin in the kidney was partially inhibited by antioxidant therapy using selenium, glutathione, flavonoids, and superoxide dismutase.

  15. Evaluation of protective effects of water extract of Spirulina platensis (blue green algae on cisplatin-induced lipid peroxidation

    Directory of Open Access Journals (Sweden)

    Ray S

    2007-01-01

    Full Text Available Attempt has been made to evaluate free radical scavenging activity of water extract of Spirulina platensis on cisplatin-induced lipid peroxidation using some common laboratory markers. In this present study goat liver has been used as lipid source. This in vitro evaluation was done by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione and nitric oxide content of tissue homogenates. The results suggest that cisplatin could induce lipid peroxidation to a significant extent and it was also found that water extract of the algae has the ability to suppress the cisplatin-induced toxicity.

  16. Protective Effect of Aqueous and Ethanolic Extracts of Portulaca Oleracea Against Cisplatin Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Gholamreza Karimi

    2010-04-01

    Full Text Available Objective(sPortulaca oleracea L. is a herbaceous weed from portulacaceae family. It can be found in many parts of the world. Modern pharmacological studies have demonstrated that P. oleracea have antioxidant effects. The protective effect of aqueous and ethanolic extract of P. oleracea against cisplatin-induced renal toxicity was studied in rats.Materials and MethodsSingle intraperitoneal injection of 4 mg/kg cisplatin was administrated to rats. After 5 days, blood urea nitrogen (BUN and serum creatinine (Scr concentration were determined. Effect of aqueous and ethanolic extracts, before and after cisplatin injection on BUN and Scr, as well as morphological renal damage, was evaluated. ResultsIt was indicated that treatment with aqueous and ethanolic extracts of P. oleracea in the highest dose (0.8 and 2 g/ kg, 6 and 12 hr before cisplatin injection reduced BUN and Scr. Tubular necrotic damage was not observed either. ConclusionResults suggest that P. oleracea extract may protect against cisplatin-induced renal toxicity and might serve as a novel combination agent with cisplan to limit renal injury.

  17. Effects of Roselle and Ginger on cisplatin-induced reproductive toxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Amr Amin; AlaaEldin A. Hamza

    2006-01-01

    Aim: To evaluate the protective effects of Hibiscus sabdariffa (Roselle) and Zingiber officinale (Ginger) against cisplatin-induced reproductive toxicity in rats and to study the mechanisms underlying these effects. Methods:which began 21 days before a single cisplatin I.p. Injection (10 mg/kg body weight). Results: Extracts of H. Sabdariffa and Z. Officinale reduced the extent of cisplatin-induced sperm abnormality and enhanced sperm motility. Both extracts restored the control level of malondialdehyde (MDA) (lipid peroxidation marker) in the cisplatin-treated testis.The cisplatin injection induced decline in the levels of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were significantly reversed to control levels in groups where cisplatin was preceded by the administration of either H. Sabdariffa or Z. Officinale. Conclusion: Both H. Sabdariffa and Z. Officinale treatment increased the activities of testicular antioxidant enzymes and restored sperm motility of cisplatin-treated rats. The protective effects of tested plants are, therefore, suggested to be mediated by their potent antioxidant activities.

  18. Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death.

    Science.gov (United States)

    Zhou, H; Miyaji, T; Kato, A; Fujigaki, Y; Sano, K; Hishida, A

    1999-12-01

    To clarify the pathophysiologic role of apoptosis in acute renal failure (ARF), we examined whether the attenuation of cisplatin-induced ARF is associated with the change in the degree of apoptotic cell death. The administration of cisplatin (CDDP) (6 mg/kg body weight) in rats induced ARF at day 5, as manifested by a significant increase in serum creatinine (Scr) and tubular damage. CDDP-induced apoptotic cell death was confirmed by electron microscopic examination, agarose gel electrophoresis, and increased cells positive for TaT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) in the outer medulla of the kidney. Treatment with dimethylthiourea (DMTU)--a scavenger of hydroxyl radicals--or glycine abrogated CDDP-induced increases in Scr, the tubular damage score, and the number of TUNEL-positive cells. Pretreatment with uranyl acetate (UA) induced a significant expression of Bcl-2 in the kidney and ameliorated CDDP-induced increases in Scr, the tubular damage score, and TUNEL-positive cells in the outer stripe of the outer medulla. Our findings indicate (1) that the attenuation of CDDP-induced ARF was associated with less apoptotic cell death and (2) that the induction of the anti-apoptotic protein Bcl-2 attenuated apoptosis and tubular damage. Our results suggest that apoptotic cell death may play an important role in the development of cisplatin-induced ARF. PMID:10595794

  19. Evaluating the various phases of cisplatin-induced emesis in rats.

    Science.gov (United States)

    Shi, Jun

    2014-11-01

    Use of cisplatin as a chemotherapeutic agent causes acute and delayed emesis. Kaolin, saccharin solution and normal feed consumption have been evaluated as an index of cisplatin-induced emesis in rats; however, the most preferable of these methods for evaluating the various phases of emesis remains unclear. In the current study, kaolin, saccharin solution and normal feed consumption following cisplatin administration (6 mg/kg intraperitoneally) were simultaneously investigated in rats. Kaolin consumption increased significantly following cisplatin administration and was attenuated by granisetron administration 0-24 h following the injection. Saccharin solution consumption, however, decreased significantly 0-48 h following cisplatin administration, however, was attenuated by administration of granisetron within 0-24 h only. A reduced intake of normal feed was observed in the control group and was reversed by granisetron within the 0-72 h period. The present study indicates that kaolin consumption may be evaluated as an index of cisplatin-induced acute emesis and saccharin solution consumption may be evaluated as an index of delayed emesis, while normal feed consumption as an indicator of anorexia nervosa may be suitable to evaluate all phases of emesis and serve as an indicator of quality of life. PMID:25289087

  20. Protective effect of speman on cisplatin-induced testicular and epididymal toxicity in mice

    Directory of Open Access Journals (Sweden)

    S B Sainath

    2011-01-01

    Full Text Available Testicular cancer is the most common cancer affecting men of reproductive age. Advances in treatment of the disease, which includes the administration of cisplatin, have brought the 5-year survival rate to over 90%. This high cure rate, coupled with young age of patients, makes elucidation of the impact of the treatment on reproduction become increasingly important. The objective of the present study was to investigate the protective effect of speman, a non-hormonal herbal formulation, on cisplatin-induced suppressed male reproductive health in mice. Male mice were treated with cisplatin or speman alone or in combination and assessed for spermatogenesis and steroidogenesis. Significant decrease in the weights of testes and epididymis was observed in cisplatin treated animals. Injection of cisplatin significantly decreased epididymal sperm count, viable sperms, motile sperms and hypo-osmotic swelling (HOS-tail coiled sperms with a significant reduction in the testicular steroidogenic enzyme activities and serum testosterone levels, whereas co-administration of speman with cisplatin showed a significant improvement in the selected reproductive parameters over cisplatin alone treated mice indicating the beneficial effect of speman to combat cisplatin-induced suppressed reproduction in male mice.

  1. Demarcation of secondary hyperalgesia zones

    DEFF Research Database (Denmark)

    Ringsted, Thomas K; Enghuus, Casper; Petersen, Morten A; Werner, Mads U

    2015-01-01

    of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). NEW METHOD: The study was a...... SHAs (P<0.0001). No day-to-day or observer-to-observer differences in SHAs were observed. Intraclass correlation coefficients, in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability between observers. COMPARISON WITH EXISTING METHODS: No standardized approach in SHA......-assessment has hitherto been presented. CONCLUSIONS: This is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used....

  2. The Protective Effect of mammalian Target of Rapamycin (mTOR in Cisplatin Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Kultigin Turkmen

    2009-05-01

    Full Text Available "nCisplatin, a simple inorganic compound, has been one of the leading antitumor drugs especially for solid tumors for near 30 years. The mechanisms of cisplatin include denaturation of DNA and cell mitochondria, arresting cell cycle in the G2 phase and eventually causing apoptosis, inflammation, necrosis and death in cells. Apoptosis is a process of programmed cell death through cystein proteases named ‘caspases'. Pathways of caspase-mediated apoptosis can classified as ‘mitochondrial' pathway and ‘death receptor' pathway Especially caspase-3 plays a crucial role in cisplatin-induced nephrotoxicity through the pathways of apoptosis. The mammalian target of rapamycin (mTOR, is a serine/threonine kinase that regulates both cell growth and cell cycle progression through the phosphotidyl 3 kinase (PI3K/protein kinase B (Akt signaling pathway. mTOR regulates both cell growth, cell cycle progression and angiogenesis. By targeting mTOR, the immunsuppressant and antiproliferative agent Rapamycin inhibits signals required for cell cycle progression, cell growth, cell proliferation and angiogenesis. Angiogenesis is extremely important in tumor progression and metastasis. Although rapamycin is proapoptotic agent especially in cancers, there is an evidence that rapamycin can also have antiapoptotic properties through pleiotropic function in the regulation of cell death depending on the cell type and activation state as well as downstream targets of antiapoptotic molecules such as p53 and Bcl-2 proteins. Activation of caspase signaling pathways and dysregulation of pro- and antiapoptotic Bcl-2 proteins have been described previously. So there are links between the mTOR and caspase signaling pathways. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity such as acute tubuler necrosis (ATN causing acute renal failure (ARF. Several agents have been tested to see whether they could

  3. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E; Issinger, Olaf-Georg; Stenvang, Jan

    2007-01-01

    future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells are...... parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for...

  4. Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice

    DEFF Research Database (Denmark)

    Hojman, Pernille; Fjelbye, Jonas; Zerahn, Bo;

    2014-01-01

    % (P<0.001), maintained lean body mass (P<0.001) and muscle strength (P<0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may......Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight......, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P<0.001), lean body mass (20.6%, P = 0.001), as well as anorexia...

  5. Selective Cyclooxygenase-2 Inhibitor Prevents Cisplatin-induced Tumorigenesis in A/J Mice

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    Okada,Toshiaki

    2012-06-01

    Full Text Available Cisplatin is used to treat lung cancer;however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2 inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups:group 1, no treatment;group 2, low-dose celecoxib (150mg/kg;group 3, high-dose celecoxib (1,500mg/kg;group 4, cisplatin alone;group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62mg/kg, i.p. once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p<0.05, group 4 vs. group 6. Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p<0.01, group 4 vs. group 6.

  6. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

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    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  7. Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer.

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-02-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDH(high)CD44(high))]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatin-sensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDH(high)CD44(high) immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation (indicative of stemness) was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK) phosphorylation (indicative of differentiation processes) was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  8. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer12

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high)]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation (indicative of stemness) was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK) phosphorylation (indicative of differentiation processes) was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs and suggest

  9. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Paolo B Abada

    Full Text Available Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4 and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells.

  10. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

    Science.gov (United States)

    Abada, Paolo B; Howell, Stephen B

    2014-01-01

    Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4) and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells. PMID:24475288

  11. Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats

    OpenAIRE

    Elhusseini, Fatma M; Saad, Mohamed-Ahdy A.A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; ALSAYED, AZIZA; El-dusoky, Sara; SHEASHAA, HUSSEIN; Abdel-Ghaffar, Hassan; Sobh, Mohamed

    2016-01-01

    Background/Aims: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system o...

  12. Cisplatin induces primary necrosis through poly(ADP-ribose) polymerase 1 activation in kidney proximal tubular cells

    OpenAIRE

    Park, Seulgee; Yoon, Sang Pil; Kim, Jinu

    2015-01-01

    Treatment with cisplatin for cancer therapy has a major side effect such as nephrotoxicity; however, the role of poly (ADP-ribose) polymerase 1 (PARP1) in necrosis in response to cisplatin nephrotoxicity remains to be defined. Here we report that cisplatin induces primary necrosis through PARP1 activation in kidney proximal tubular cells derived from human, pig and mouse. Treatment with high dose of cisplatin for 4 and 8 hours induced primary necrosis, as represented by the percentage of prop...

  13. The effects of oral grape seed extract on Cisplatin-induced cytogenotoxicity in mice

    International Nuclear Information System (INIS)

    The present investigation was directed to study the possible chemoprotective activity of orally administered grape seed extract (GSE) against cisplatin-induced cytotoxicity and genotoxicity towards mouse somatic and germinal cells in vivo. Pretreatment of mice with GSE (100mg/kg/day) for 7 days and simultaneously with a single dose of cisplatin (2.2 or 5.5 mg/kg, i.p.) for another day, significantly reduced the frequency of bone marrow micronucleated polychromatic erythrocytes by factors of 1.9 and 1.28, respectively. Furthermore, GSF caused a reduction in bone marrow suppression induced by cisplatin treatment, particularly before the lower dose. In mail germline, orally administration of GSE (100mg/kg/day) for 7 consecutive days before and 7 consecutives days after treatment with a single dose of cisplatin (2.2 or 5.5 mg/kg, i.p.), significantly elevated the levels of sperm motility reduced by cisplatin treatment. Furthermore, GSE significantly decreased the elevated levels sperm head abnormality induced with cisplatin by factors of 1.6 and 1.2, respectively. Our results indicate that GSE plays a role in attenuating the genotoxicity induced by cisplatin and many provide the development of secondary malignancy and abnormal reproductive outcomes risk. (author)

  14. Amelioration of cisplatin induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract

    Directory of Open Access Journals (Sweden)

    Joy Jisha

    2008-01-01

    Full Text Available Background: Cisplatin is one of the most effective chemotherapeutics against a wide range of cancers including head, neck, ovarian and lung cancers. But its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of the present study is to investigate whether the hydro-alcoholic extract of Rubia cordifolia could decrease the intensity of toxicity in Swiss albino mice. Materials and Methods: Cisplatin at a dose of 12 mg/kg body wt was administered intraperitoneally to Swiss albino mice. Another set of animals was given hydro-alcoholic extract of Rubia cordifolia at different doses along with cisplatin treatment. The antioxidant levels, serum creatinine, serum urea etc. were analyzed. Results: The extract could significantly decrease the cisplatin induced nephrotoxicity as inferred from the tissue antioxidant status in the drug administered animals. Remarkable change was observed in serum creatinine and urea levels. Lipid peroxidation in the kidney and liver tissues was also considerably reduced in Rubia cordifolia extract treated animals. Conclusion: Hydro-alcoholic extracts of Rubia cordifolia are effective in reducing the renal damage caused by the cancer chemotherapeutic drug cisplatin. Since Rubia cordifolia has been in use as an important ingredient in the traditional Ayurvedic system of medicine, it could be safe and beneficial to use this herbal extract as an adjuvant to ameliorate renal damage in patients undergoing cancer chemotherapy with cisplatin.

  15. Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice.

    Directory of Open Access Journals (Sweden)

    Pernille Hojman

    Full Text Available Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001, lean body mass (20.6%, P = 0.001, as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001 and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001, maintained lean body mass (P < 0.001 and muscle strength (P < 0.001, reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.

  16. Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Wei ZHAO; Zhong Xiang LIN; Zhi Qian ZHANG

    2004-01-01

    To examine the role of gap junctions in cell senescence,the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts.Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore,cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis,elevation of p53 expression,loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

  17. Mitochondrial modulation by Epigallocatechin 3-Gallate ameliorates cisplatin induced renal injury through decreasing oxidative/nitrative stress, inflammation and NF-kB in mice.

    Science.gov (United States)

    Pan, Hao; Chen, Jun; Shen, Kezhen; Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

    2015-01-01

    Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

  18. Fetal kidney stem cells ameliorate cisplatin induced acuterenal failure and promote renal angiogenesis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To investigate whether fetal kidney stem cells(fKSC) ameliorate cisplatin induced acute renal failure(ARF) in rats and promote renal angiogenesis.METHODS: The fKSC were isolated from rat fetusesof gestation day 16 and expanded in vitro up to 3rdpassage. They were characterized for the expressionof mesenchymal and renal progenitor markers by flowcytometry and immunocytochemistry, respectively.The in vitro differentiation of fKSC towards epitheliallineage was evaluated by the treatment with specificinduction medium and their angiogenic potential bymatrigel induced tube formation assay. To study theeffect of fKSC in ARF, fKSC labeled with PKH26 wereinfused in rats with cisplatin induced ARF and, the bloodand renal tissues of the rats were collected at differenttime points. Blood biochemical parameters werestudied to evaluate renal function. Renal tissues wereevaluated for renal architecture, renal cell proliferationand angiogenesis by immunohistochemistry, renal cellapoptosis by terminal deoxynucleotidyl transferase nickendlabeling assay and early expression of angiogenicmolecules viz . vascular endothelial growth factor (VEGF),hypoxia-inducible factor (HIF)-1α and endothelial nitricoxide synthase (eNOS) by western blot.RESULTS: The fKSC expressed mesenchymal markersviz . CD29, CD44, CD73, CD90 and CD105 as well as renal progenitor markers viz . Wt1, Pax2 and Six2. Theyexhibited a potential to form CD31 and Von Willebrandfactor expressing capillary-like structures and could bedifferentiated into cytokeratin (CK)18 and CK19 positiveepithelial cells. Administration of fKSC in rats with ARF ascompared to administration of saline alone, resulted in asignificant improvement in renal function and histology onday 3 (2.33 ± 0.33 vs 3.50 ± 0.34, P 〈 0.05) and on day7 (0.83 ± 0.16 vs 2.00 ± 0.25, P 〈 0.05). The infusedPKH26 labeled fKSC were observed to engraft in damagedrenal tubules and showed increased proliferation andreduced

  19. Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice.

    Science.gov (United States)

    Harris, Hannah M; Sufka, Kenneth J; Gul, Waseem; ElSohly, Mahmoud A

    2016-08-01

    Sativex, a cannabinoid extract with a 1 : 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy. PMID:27214593

  20. Hepatoprotective effect of Ficus religiosa latex on cisplatin induced liver injury in Wistar rats

    Directory of Open Access Journals (Sweden)

    Yogesh C. Yadav

    2015-06-01

    Full Text Available AbstractFicus religiosa L., Moraceae, is widely planted in the tropics. The chemical constituents of F. religiosa include tannin, saponin gluanol acetate, β-sitosterol, leucoanthocyanidin, and leucoanthocyanin. These are used for the treatment of pain, inflammation, impotence, menstrual disturbances, and urine related problems, and as uterine tonic. The present study aimed to evaluate hepatoprotective effects of F. religiosa latex on cisplatin induced liver injury in Wistar rats. In experimental protocol contained five groups of rats (n = 6. In which, group I (control was administered acacia (2%, w/v of 5 ml/kg throughout the experiment for 16 days. The group II (cisplatin treated was administered single dose of cisplatin (7.5 mg/kg i.p. on 1st day. Group III (extract control was administered 300 mg/kg p.o. of extract for 1stto 10th day. Group IV (Protective was administered extract (300 mg/kg p.o. of F. religiosa latex for 1st to 10th day and administered single dose of cisplatin (7.5 mg/kg i.p. on 11th day and group V (Curative received single dose of cisplatin (7.5 mg/kg i.p. on day 1st, and administered extract (300 mg/kg p.o. from 7th to 16thdays. On the 6th day in cisplatin treated, 10th day in extract control and 16th day in control, protective and curative, blood withdrawn from retro-orbital sinus of rats for biochemical estimation for serum and dissected out the livers for estimation of antioxidant enzymes and histopathological works. The cisplatin-treated group 2 showed a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatocytes cells degeneration inflammatory infiltrate and necrosis it's were significantly (**p < 0.01 alleviates by protective groups.

  1. Ondansetron Can Enhance Cisplatin-Induced Nephrotoxicity via Inhibition of Multiple Toxin and Extrusion Proteins (MATEs)

    Science.gov (United States)

    Li, Qing; Guo, Dong; Dong, Zhongqi; Zhang, Wei; Zhang, Lei K.; Huang, Shiew-Mei; Polli, James E.; Shu, Yan

    2013-01-01

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients. PMID:24001450

  2. Chronic low vitamin intake potentiates cisplatin-induced intestinal epithelial cell apoptosis in WNIN rats

    Institute of Scientific and Technical Information of China (English)

    Bodiga Vijayalakshmi; Boindala Sesikeran; Putcha Udaykumar; Subramaniam Kalyanasundaram; Manchala Raghunath

    2006-01-01

    AIM: To investigate if cisplatin alters vitamin status and if VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar/NIN (WNIN) male rats.METHODS: Weanling, WNIN male rats (n = 12 per group) received adlibitum for 17 wk: control diet (20%protein) or the same with 50% vitamin restriction. They were then sub-divided into two groups of six rats each and administered cisplatin (2.61 mg/kg bodyweight)once a week for three wk or PBS (vehicle control).Intestinal epithelial cell (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeath assay and DNA fragmentation. Structural and functional integrity of the villus were assessed by villus height /crypt depth ratio and activities of alkaline phosphatase,lys, ala-dipeptidyl amino-peptidase, respectively. To assess the probable mechanism(s) of altered apoptosis,oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined.RESULTS: Cisplatin per se decreased plasma vitamin levels and they were the lowest in VR animals treated with cisplatin. As expected VR increased only villus apoptosis, whereas cisplatin increased stem cell apoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and crypt regions and was associated with higher levels of TBARS,protein carbonyls and caspase-3 activity, but lower GSH concentrations. VR induced decrease in Bcl-2 expression was further lowered by cisplatin. Bax expression,unaffected by VR was increased on cisplatin treatment.Mucosal functional integrity was severely compromised in cisplatin treated VR-rats.CONCLUSION: Low intake of vitamins increases the sensitivity of rats to cisplatin and promotes intestinal epithelial cell apoptosis.

  3. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    International Nuclear Information System (INIS)

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  4. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  5. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

    Directory of Open Access Journals (Sweden)

    He Fan

    2010-12-01

    Full Text Available Abstract Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA and N-acetyl-L-cysteine (NAC dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.

  6. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.

    Science.gov (United States)

    Chtourou, Yassine; Aouey, Baktha; Aroui, Sonia; Kebieche, Mohammed; Fetoui, Hamadi

    2016-01-01

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease. PMID:26612654

  7. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    El-Naga, Reem N., E-mail: reemelnaga@hotmail.com

    2014-01-01

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  8. Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses

    DEFF Research Database (Denmark)

    Fritz, Gerhard; Issinger, Olaf-Georg; Olsen, Birgitte Brinkmann

    2009-01-01

    DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected...... by phosphorylation of JNK and H2AX). In the case of resorufin no interference with the stress-signaling pathway is observed, supporting the notion that TBB and DMAT interfere with upstream molecules involved in genotoxic stress signaling. We have also tested the protein kinase CK2 inhibitors with respect to cell...

  9. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    International Nuclear Information System (INIS)

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  10. Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury

    International Nuclear Information System (INIS)

    Highlights: • Chlorogenic acid attenuated cisplatin-induced renal oxidative stress by reducing the expression of 4-HNE, HO-1 and CYP2E1. • The inhibition of inflammatory response was achieved through the reduction of TNF-α and COX-2 expression. • The expression of p53, Bax, active caspase-3 and LC3B was suppressed, suggesting the inhibition of apoptosis and autophagy. • Attenuation of Mrp1 and Mrp2 expression and the increase in Oct2 expression indicated reduced burden of tubular cells. • The recovery of kidneys form cisplatin injury was accompanied by the suppression of cyclin D1 and augmented PCNA expression. - Abstract: The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30 mg/kg for two successive days, 48 h after intraperitoneal injection of CP (13 mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery

  11. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qing [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Guo, Dong [Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Dong, Zhongqi [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Zhang, Wei [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Zhang, Lei; Huang, Shiew-Mei [Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD (United States); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2013-11-15

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT{sub 3}) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic

  12. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    International Nuclear Information System (INIS)

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic cisplatin

  13. Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jun; Sun, Kang [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Ni, Lijuan; Wang, Xufang [School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui (China); Wang, Dongxu [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

    2012-02-01

    Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

  14. Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress

    Science.gov (United States)

    2014-01-01

    and α-tocopherol can protect cisplatin-induced hepatotoxicity including the biochemical, histological and molecular aspects. The down-regulations of NADPH oxidase gene expression may be involved in abrogating oxidative stress via reduction of reactive oxygen species (ROS) production. PMID:24674233

  15. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Sang Yong [Department of Diagnostic Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Han, Myung Kwan [Department of Microbiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kim, Duk Hoon [Division of Forensic Medicine, National Forensic Service, Seoul (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

  16. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  17. Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Karwasra, Ritu; Kalra, Prerna; Gupta, Yogendra Kumar; Saini, Deepika; Kumar, Ajay; Singh, Surender

    2016-07-13

    Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p stress and inflammation. PMID:27273121

  18. Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD.

    Science.gov (United States)

    Torres, Richard; Velazquez, Heino; Chang, John J; Levene, Michael J; Moeckel, Gilbert; Desir, Gary V; Safirstein, Robert

    2016-04-01

    Traditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD. Highly labor-intensive serial sectioning studies have demonstrated that three-dimensional perspective can reveal useful morphologic information on cisplatin-induced CKD. By applying the new technique of multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin-induced CKD, we obtained detailed morphologic and collagen reconstructions of millimeter-thick renal sections that provided new insights into pathophysiology. Quantitative analysis revealed that a major long-term cisplatin effect is reduction in the number of cuboidal cells of the glomerular capsule, a change we term the "uncapped glomerulus lesion." Glomerulotubular disconnection was confirmed, but connection remnants between damaged tubules and atubular glomeruli were observed. Reductions in normal glomerular capsules corresponded to reductions in GFR. Mild increases in collagen were noted, but the fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume and number remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass decreased. In conclusion, new observations were made possible by using clearing MPM, demonstrating the utility of this technique for studies of renal disease. This technique should prove valuable for further characterizing the evolution of CKD with cisplatin therapy and of other conditions. PMID:26303068

  19. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    International Nuclear Information System (INIS)

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity

  20. Assessing cisplatin-induced ototoxicity and otoprotection in whole organ culture of the mouse inner ear in simulated microgravity.

    Science.gov (United States)

    Tropitzsch, Anke; Arnold, Heinz; Bassiouni, Mohamed; Müller, Andrea; Eckhard, Andreas; Müller, Marcus; Löwenheim, Hubert

    2014-06-16

    Cisplatin is a widely used anti-cancer drug. Ototoxicity is a major dose-limiting side-effect. A reproducible mammalian in-vitro model of cisplatin ototoxicity is required to screen and validate otoprotective drug candidates. We utilized a whole organ culture system of the postnatal mouse inner ear in a rotating wall vessel bioreactor under "simulated microgravity" culture conditions. As previously described this system allows whole organ culture of the inner ear and quantitative assessment of ototoxic effects of aminoglycoside induced hair cell loss. Here we demonstrate that this model is also applicable to the assessment of cisplatin induced ototoxicity. In this model cisplatin induced hair cell loss was dose and time dependent. Increasing exposure time of cisplatin led to decreasing EC50 concentrations. Outer hair cells were more susceptible than inner hair cells, and hair cells in the cochlear base were more susceptible than hair cells in the cochlear apex. Initial cisplatin dose determined the final extent of hair cell loss irrespective if the drug was withdrawn or continued. Dose dependant otoprotection was demonstrated by co-administration of the antioxidant agent N-acetyl l-cysteine. The results support the use of this inner ear organ culture system as an in vitro assay and validation platform for inner ear toxicology and the search for otoprotective compounds. PMID:24709139

  1. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts

    Science.gov (United States)

    Cao, Long-Hui; Li, Hui-Ting; Lin, Wen-Qian; Tan, Hong-Ying; Xie, Lan; Zhong, Zhong-Jian; Zhou, Jian-Hua

    2016-01-01

    Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an in vivo nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models in vitro and in vivo by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. PMID:26729257

  2. Effect of Insulin-Like Growth Factor II on Protecting Myoblast Cells Against Cisplatin-Induced Apoptosis Through p70 S6 Kinase Pathway

    Directory of Open Access Journals (Sweden)

    Xiaolin Wan

    2002-01-01

    Full Text Available Insulin-like growth factor. (IGF-II is overexpressed in a variety of human tumors and has both mitogenic and antiapoptotic activity. Although the mechanisms of IGFII-induced proliferation have been well studied, the mechanisms underlying its survival signaling have been less well characterized. In this report, we investigated the role of IGF-II on cisplatin-induced apoptosis. We found that IGF-II overexpression was associated with an increase in p70 ribosomal protein S6 kinase. (p70 S6K. Cisplatin treatment of. (321312 mouse myoblasts led to cell death associated with an inhibition of p70 S6K activity. Endogenous or exogenous IGF-II addition to. (321312 cells caused protection to cisplatin-induced apoptosis. This protection was associated in both cases with an increase in p70 S6K basal activity as well as resistance to cisplatin-induced decreased activity. Blockade of p70 S6K activation by rapamycin abrogated the IGF-II-mediated protection of cells to cisplatininduced apoptosis. Furthermore, treatment of IGF-IIoverexpressing Rh30 and CTR rhabdomyosarcoma cells with rapamycin restored sensitivity to cisplatininduced apoptosis. These data together suggest that IGF-II-associated protection to cisplatin-induced apoptosis is mediated through an activation of the p70 S6K pathway. Thus, inhibition of the p70 S6 pathway may enhance chemotherapy-induced apoptosis in the treatment of IGF-II-overexpressing tumors.

  3. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    International Nuclear Information System (INIS)

    DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line

  4. Anthocyanin - Rich Red Dye of Hibiscus Sabdariffa Calyx Modulates Cisplatin-induced Nephrotoxicity and Oxidative Stress in Rats.

    Science.gov (United States)

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Agbebi, Oluwaseun J; Akinyemi, Ayodele J

    2013-12-01

    This study sought to investigate the protective effect of dietary inclusion of Hibiscus sabdariffa calyx red dye on cisplatin-induced nephrotoxicity and antioxidant status in rats. Adult male rats were randomly divided into four groups of six animals each. Groups I and II were fed basal diet while groups III and IV were fed diets containing 0.5% and 1% of the dye respectively for 20 days prior to cisplatin administration. Nephrotoxicity was induced by a single dose intraperitoneal administration of cisplatin (7 mg/kg b.w) and the experiment was terminated 3 days after. The kidney and plasma were studied for nephrotoxicity and oxidative stress indices. Cisplatin administration caused a significant (Psabdariffa dye could be attributed to its anthocyanin content. PMID:24711761

  5. D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering ATPase activities and oxidative stress in guinea pigs

    International Nuclear Information System (INIS)

    Cisplatin has been used as a chemotherapeutic agent to treat many kinds of malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been reported. However, the underlying biochemical change in the inner ear or central vestibular nervous system is not fully understood. In this study, we attempted to examine whether cisplatin-induced vestibulotoxicity and D-methionine protection were correlated with the changes of ATPase activities and oxidative stress of ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory center of VOR system) of guinea pigs. By means of a caloric test coupled with electronystagmographic recordings, we found that cisplatin exposure caused a dose-dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of slow phase velocity (SPV). In addition, cisplatin significantly inhibited the Na+, K+-ATPase and Ca2+-ATPase activities in the ampullary tissue with a good dose-response relationship but not those of cerebellar cortex. Regression analysis indicated that a decrease of SPV was well correlated with the reduction of Na+, K+-ATPase and Ca2+-ATPase activities of the ampullary tissue. D-Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in a correlated manner. Moreover, cisplatin exposure led to a significant dose-dependent increase of lipid peroxidation and nitric oxide concentrations of the vestibules, which could be significantly suppressed by D-methionine. However, cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated cisplatin-induced vestibulotoxicity associated with ionic disturbance through its antioxidative property

  6. Fear of pain potentiates nocebo hyperalgesia

    OpenAIRE

    Aslaksen PM; Lyby PS

    2015-01-01

    Per M Aslaksen,1 Peter S Lyby2 1Department of Psychology, Research Group for Cognitive Neuroscience, The Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; 2Catosenteret Rehabilitation Center, Son, Norway Abstract: Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hype...

  7. Fear of pain potentiates nocebo hyperalgesia

    OpenAIRE

    Aslaksen, Per

    2015-01-01

    Per M Aslaksen,1 Peter S Lyby2 1Department of Psychology, Research Group for Cognitive Neuroscience, The Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; 2Catosenteret Rehabilitation Center, Son, Norway Abstract: Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental noc...

  8. Acetaminophen prevents hyperalgesia in central pain cascade

    OpenAIRE

    Crawley, Brianna; Saito, Osamu; Malkmus, Shelle; Fitzsimmons, Bethany; Hua, Xiao-Ying; Yaksh, Tony L.

    2008-01-01

    Acetaminophen is an analgesic and antipyretic drug believed to exert its effect through interruption of nociceptive processing. In order to determine whether this effect is due to peripheral or central activity, we studied the efficacy of systemic (oral) and intrathecal (IT) application of acetaminophen in preventing the development of hyperalgesia induced through the direct activation of pro-algogenic spinal receptors. Spinal administration of substance P (SP, 30 nmol, IT) in rats produced a...

  9. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo...

  10. Role of electrolytes disturbances and Na(+)-K(+)-ATPase in cisplatin - induced renal toxicity and effects of ethanolic extract of Cichorium intybus.

    Science.gov (United States)

    Noori, Shafaq; Mahboob, Tabassum

    2012-10-01

    Cisplatin is known by its toxicity by disturbing electrolytes homeostasis. Thus we aimed to find out the role of herbal plant Cichorium intybus on Cisplatin - induced toxicity. 24 male Albino Wistar rats were randomly divided into 4 groups: Group I is termed as untreated control; Group II is Cisplatin control and received 3 mg/ kg b.w.; i.p.; Group III received C. intybus ethanolic extract at a dose of 500 mg/kg b.w. orally for 10 consecutive days and Group IV is Cisplatin + C. intybus pretreated group. C. intybus is given 30 minutes prior to Cisplatin. Cisplatin - induced electrolytes disturbances is indicated by increase Intra - erythrocyte sodium content, decreased plasma magnesium, calcium and Intra-erythrocyte Na(+)-K(+)-ATPase which implicates the renal toxicity. At a dose of 500 mg/kg b.w. of C. Intybus pretreatment showed partial counter action on the electrolytes imbalances and Na(+)-K(+)-ATPase activity. PMID:23010005

  11. Antioxidantes da dieta como inibidores da nefrotoxicidade induzida pelo antitumoral cisplatina Dietary antioxidants as inhibitors of cisplatin-induced nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Lusânia Maria Greggi Antunes

    2004-03-01

    Full Text Available A cisplatina é uma droga antineoplásica altamente efetiva contra vários tipos de cânceres humanos, tais como tumores do testículo e ovário, câncer da cabeça e pescoço e câncer do pulmão. Entretanto, a nefrotoxicidade é um dos principais efeitos colaterais da terapia com a cisplatina. A gravidade da nefrotoxicidade induzida pela cisplatina está relacionada com a concentração de platina nos rins. As evidências mostram que a nefrotoxicidade induzida pela cisplatina é atribuída ao dano oxidativo resultante da geração de radicais livres, e que a administração de antioxidantes é eficiente na inibição destes efeitos colaterais. Uma abordagem alternativa para proteger os roedores dos efeitos colaterais da cisplatina é o uso de conhecidos antioxidantes da dieta. Alguns estudos têm sido realizados para diminuir a peroxidação lipídica e os efeitos citotóxicos induzidos pela cisplatina, com o emprego de antioxidantes da dieta, tais como, selenito de sódio, vitaminas C e E, curcumina e o carotenóide bixina. Nós sugerimos que aqueles antioxidantes da dieta têm efeito nefroprotetor, e que os mecanismos antioxidantes destes compostos deveriam ser explorados durante a quimioterapia com a cisplatina.Cisplatin is a highly effective antineoplastic drug used against several types of human cancers, such as testicular and ovarian tumors; head and neck; and lung cancer. However, nephrotoxicity is one of the most important side-effects of cisplatin therapy. The severity of cisplatin nephrotoxicity is related to platinum concentration in the kidneys. There is a growing amount of evidence that cisplatin-induced nephrotoxicity is ascribed to oxidative damage resulting from free radical generation and that the administration of antioxidants is efficient in inhibiting these side effects. An alternative approach aiming to protect rodents against cisplatin side-effects is the introduction of known dietary antioxidants. Some studies have been

  12. Evaluation of protective effects of water extract of Spirulina platensis (blue green algae) on cisplatin-induced lipid peroxidation

    OpenAIRE

    Ray S; Roy K; Sengupta Chandana

    2007-01-01

    Attempt has been made to evaluate free radical scavenging activity of water extract of Spirulina platensis on cisplatin-induced lipid peroxidation using some common laboratory markers. In this present study goat liver has been used as lipid source. This in vitro evaluation was done by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione and nitric oxide content of tissue homogenates. The results suggest that cisplatin could induce lipid peroxidation to a significant ext...

  13. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  14. Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1

    OpenAIRE

    Miyagi, Mariana Yasue Saito; Seelaender, Marilia; Castoldi, Angela; de Almeida, Danilo Candido; Bacurau, Aline Villa Nova; Andrade-Oliveira, Vinicius; Enjiu, Lucas Maceratesi; Pisciottano, Marcus; Hayashida, Caroline Yuri; Hiyane, Meire Ioshie; Brum, Patricia Chakur; Camara, Niels Olsen Saraiva; Amano, Mariane Tami

    2014-01-01

    Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI...

  15. Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice.

    Science.gov (United States)

    Garcia, Jose M; Chen, Ji-an; Guillory, Bobby; Donehower, Lawrence A; Smith, Roy G; Lamb, Dolores J

    2015-07-01

    Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms. PMID:26019260

  16. Opioid-induced hyperalgesia and burn pain.

    Science.gov (United States)

    Holtman, Joseph R; Jellish, W Scott

    2012-01-01

    The treatment of pain produced during the management of burn injury has been an ongoing problem for physicians caring for these patients. The main therapeutic option for analgesia has been the repeated and prolonged use of opioids. The adverse effects of opioids are well known but the long term use of opioids which produces tolerance with accompanying dose escalation and dependence is most problematic. Another potentially important consequence of opioid exposure that sometimes masks as tolerance is that of opioid induced hyperalgesia. This syndrome is manifest as enhanced pain, sensitivity and loss of analgesic efficacy in patients treated with opioids who actually become sensitized to painful stimuli. This article focuses on the treatment of burn pain and how current analgesic therapies with opioids may cause hyperalgesia and affect the adequacy of treatment for burn pain. This article also provides possible modalities to help therapeutically manage these patients and considers future analgesic strategies which may help to improve pain management in this complicated patient population. PMID:23143613

  17. Differences in estimates of cisplatin-induced cell kill in vitro between colorimetric and cell count/colony assays.

    Science.gov (United States)

    Henriksson, Eva; Kjellén, Elisabeth; Wahlberg, Peter; Wennerberg, Johan; Kjellström, Johan H

    2006-01-01

    The aim of this study was to evaluate some bioassays that are different in principle: cell counting, colony forming assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB), crystal violet, and alamarBlue, with respect to their ability to measure cisplatin-induced cell death of in vitro-cultivated squamous cell carcinoma of the head and neck (SCCHN). Cisplatin was applied in concentrations of 1.0, 5.0, 10.0, 50.0, and 100 microM. The cells were incubated for 1 h, and the cell survival was measured 5 d after treatment. We found the colorimetric assays and cell counting to be comparable. The colony forming assay indicated a higher degree of cell kill compared with the other techniques. Measurement of cell survival after treatment with cisplatin can be done by use of any of the above tested assays. However, the majority of SCCHN cell lines available do not form colonies easily, or at all. Therefore, comparing the chemosensitivity between such cell lines is limited to alternative assays. In this respect, any of the tested colorimetric assays can be used. However, they seem to underestimate cell kill. Cell counting is also an alternative. This technique, however, is time consuming and operator dependent, as in the case of manual counting, or relatively expensive when counting is performed electronically, compared with the colorimetric assays. PMID:17316066

  18. Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

    Directory of Open Access Journals (Sweden)

    Maria José Santiago

    Full Text Available To design an experimental pediatric animal model of acute kidney injury induced by cisplatin.Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg. The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study.41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage.a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

  19. Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets

    Science.gov (United States)

    Lázaro, Alberto; González, Rafael; Urbano, Javier; López, Jorge; Solana, Maria José; Toledo, Blanca; del Castillo, Jimena; Tejedor, Alberto; López-Herce, Jesús

    2016-01-01

    Objective To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. Methods Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study. Results 41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage. Conclusions a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury. PMID:26871589

  20. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance

    International Nuclear Information System (INIS)

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells

  1. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  2. Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice.

    Science.gov (United States)

    Chen, Rong-Gui; Kong, Wei-Wei; Ge, Da-Long; Luo, Ceng; Hu, San-Jue

    2011-08-01

    OBJECTIVE Low back pain is one of the most inextricable problems encountered in clinics. Animal models that imitate symptoms in humans are valuable tools for investigating low back pain mechanisms and the possible therapeutic applications. With the development of genetic technology in pain field, the possibility of mutating specific genes in mice has provided a potent tool for investigating the specific mechanisms of pain. The aim of the present study was to develop a mouse model of chronic compression of dorsal root ganglion (CCD), in which gene mutation can be applied to facilitate the studies of chronic pain. METHODS Chronic compression of L4 and L5 dorsal root ganglia was conducted in mice by inserting fine stainless steel rods into the intervertebral foramina, one at L4 and the other at L5. Mechanical allodynia and thermal hyperalgesia were examined with von Frey filaments and radiating heat stimulator, respectively. RESULTS The CCD mice displayed dramatic mechanical and thermal hyperalgesia as well as tactile allodynia in the hindpaw ipsilateral to CCD. In addition, this mechanical and thermal hyperalgesia as well as tactile allodynia was also found to spread to the contralateral hindpaw. CONCLUSION This model, combined with the possible genetic modification, will strengthen our knowledge of the underlying mechanisms of low back pain. It also favors the development of new treatment strategies for pain and hyperalgesia after spinal injury and other disorders which affect the dorsal root ganglion in humans. PMID:21788994

  3. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

    International Nuclear Information System (INIS)

    Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

  4. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat, E-mail: sarwat786@rediffmail.com

    2012-02-01

    Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

  5. Comparative analysis of cisplatin-induced nephrotoxicity in head and neck cancer and carcinoma cervix during concurrent chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Puneet Kumar Bagri

    2014-01-01

    Full Text Available Background: Cisplatin is widely used as radio sensitizer in head and neck cancer (HNC and carcinoma cervix (CaCx. This study aims to see comparative nephrotoxicity of cisplatin in HNC and in CaCx without obstructive uropathy treated by concurrent chemoradiotherapy (CCRT. Materials and Methods: Fifty patients of HNC and 50 patients of CaCx stage II/III without obstructive uropathy were included in this study. Cisplatin 50 mg intravenous weekly was given before EBRT with adequate hydration and premedication in both groups. Before chemotherapy; blood urea, serum creatinine, and glomerular filtration rate (GFR were measured. GFR was measured using 99m Tc diethylene triamine pentacaetic acid (DTPA renogram study. Results: At the end of 4 th week, blood urea level 41-45 mg% was in 40 and 4% in HNC and CaCx, respectively (P = 0.018. At the end of 3 rd and 4 th week, blood urea level >45 mg% was 10 and 6% in HNC cases, respectively. At the end of 4 th week, serum creatinine level 1.1-1.5 mg% was 50 and 8% in HNC and CaCx, respectively (P = 0.047. Serum creatinine level >1.5 mg% was 6, 8, and 22% in HNC at the end of 2 nd , 3 rd , and 4 th week, respectively. GFR <80 ml/min at the end of 4 th week was 14% in HNC and only 2% in CaCx. GFR <100ml/min was significant at the end of 4 th week (P = 0.04. Univariate analysis showed significant relation between reduced oral fluid intake and reduced GFR (P < 0.001. Conclusion: In HNC, during concurrent chemoradiation, as the 3 rd -4 th week is reached, oral mucosal reactions increase and affect oral intake which further add to the cisplatin-induced nephrotoxicity. In CaCx without obstructive uropathy, renal function impairment is less severe as oral intake of water and liquid is not much impaired.

  6. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    International Nuclear Information System (INIS)

    Highlights: ► miR-199a-5p levels were significantly decreased after cisplatin treatment. ► Cisplatin treatment induced autophagy activation. ► Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  7. High-concentration L-menthol exhibits counter-irritancy to neurogenic inflammation, thermal and mechanical hyperalgesia caused by TRPA1-agonist trans-cinnamaldehyde

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Gazerani, Parisa; Arendt-Nielsen, Lars

    2016-01-01

    volunteers. In one of two sessions, 1) 10% CA alone, 2) 40% L-menthol + 10% CA applied simultaneously were administered for 20min throughout which the subjects rated the pain intensity on a VAS0-10. Extensive quantitative sensory testing was conducted and superficial blood flow (neurogenic inflammation) was......<0.05), secondary mechanical hyperalgesia (P<0.05), and heat hyperalgesia (P<0.05), but not cold hyperalgesia. L-menthol exhibited inhibitory effects on simultaneously established pain, hypersensitivity, and neurogenic inflammation in a human TRPA1-induced pain model. Potent TRPM8-agonists could be...... useful as topical anti-hyperalgesics. The study and the trial protocol is registered and approved by the local research ethics committee under the jurisdiction of the Danish Medicines Agency no.: N-20130005. The protocol also is registered at Clinicaltrials.gov under the no.: NCT02653703. PERSPECTIVE...

  8. Spinal processing of bee venom-induced pain and hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    Jun CHEN

    2008-01-01

    Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord, which contributes to the development and maintenance of various pain-related behaviors. The unique behavioral 'pheno-types' of nociception and hypersensitivity identified in the rodent bee venom test are believed to reflect a complex pathological state of inflammatory pain and might be appropriate to the study of phenotype-based mechanisms of pain and hyperalgesia. In this review, the spinal processing of the bee venom-induced different 'phenotypes' of pain and hyperalgesia will be described. The accumulative electrophysiological, pharmacological, and behavioral data strongly suggest that different 'phenotypes' of pain and hyperalgesia are mediated by different spinal signaling pathways. Unraveling the phenotype-based mechanisms of pain might be useful in development of novel therapeutic drugs against complex clinic pathological pain.

  9. Characterization of nociceptin hyperalgesia and allodynia in conscious mice

    OpenAIRE

    Hara, Naoki; Minami, Toshiaki; Okuda-Ashitaka, Emiko; Sugimoto, Tetsuo; Sakai, Masato; Onaka, Masahiko; Mori, Hidemaro; Imanishi, Toshihiro; Shingu, Koh; Ito, Seiji

    1997-01-01

    Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with the morphine-induced allodynia and the nociceptin-evoked hyperalgesia.Nociceptin-induced allodynia was evoked by the first stimulus 5 min after i.t. injection, reached a maximum at 10...

  10. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    . METHODS: The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively. The......BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers...... duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds to...

  11. Assessment of D-methionine protecting cisplatin-induced otolith toxicity by vestibular-evoked myogenic potential tests, ATPase activities and oxidative state in guinea pigs.

    Science.gov (United States)

    Lo, Wu-Chia; Chang, Chih-Ming; Liao, Li-Jen; Wang, Chi-Te; Young, Yi-Ho; Chang, Yih-Leong; Cheng, Po-Wen

    2015-01-01

    To date, inadequate study has been devoted to the toxic vestibular effects caused by cisplatin. In addition, no electrophysiological examination has been conducted to assess cisplatin-induced otolith toxicity. The purposes of this study are thus two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met) pre-injection would protect the otolith organs against cisplatin-induced changes in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally treated once daily with the following injections for seven consecutive days: sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or a combination of d-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a 30 minute window in between. Each animal underwent the oVEMP and cVEMP tests before and after treatment. The changes in the biochemistry of the otolith organs, including membranous Na(+), K(+)-ATPase and Ca(2+)-ATPase, lipid peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests were significantly (ppigs receiving both D-met and cisplatin, the amplitudes of their oVEMP tests were significantly larger (p<0.05) than those of the cisplatin-only group, but smaller (p<0.05) than those of the saline control or D-met-only group. However, no significant difference of the amplitudes of cVEMP tests was noted among the four groups. In comparison with the other three groups, the cisplatin-only group had the lowest (ps<0.05) mean Na(+), K(+)-ATPase and Ca(2+)-ATPase, and the highest (ps<0.05) LPO and NO levels. The oVEMP tests were feasible for the evaluation of cisplatin-related otolith dysfunction. D-Met attenuated the reduced ATPase activities and increased oxidative stress induced by cisplatin

  12. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Science.gov (United States)

    Ju, Sung Min; Kang, Jun Gue; Bae, Jun Sang; Pae, Hyun Ock; Lyu, Yeoung Su; Jeon, Byung Hun

    2015-01-01

    Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2) cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM) for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells. PMID:26089934

  13. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  14. EVALUATION OF CISPLATIN-INDUCED PICA BEHAVIOUR IN RATS BY MEASURING FAECAL CARMINE-DYE EXCRETION: AN IMPROVED EXPERIMENTAL MODEL TO SCREEN SAMPLES WITH ANTI-EMETIC PROPERTIES

    Directory of Open Access Journals (Sweden)

    Rajesh S.

    2012-02-01

    Full Text Available The objective of the present study is to evaluate the Cisplatin-induced pica behaviour in rats by measuring faecal carmine dye excretion and to evaluate the anti-emetic effect of drugs on Cisplatin-induced pica behaviour in rats. Thirty-two rats were divided into 4 groups of 8 animals each. Rats from group I and II received DM water (10ml/kg p.o. Rats from group III and IV received Himalaya Anti-emetic Tablets (HAT 250 mg/kg p.o. and ondansetron 4mg/kg p.o, respectively. After one hour of the assigned treatment, all the animals except in group I were injected with Cisplatin 3mg/kg i.p. Rats in group I were injected with saline (1ml/kg i.p.. All the animals were fed with normal as well as kaolin pellets (impregnated with carmine dye. The faeces of each rat was collected after 72 hrs of drug administration and analysed for the carmine content.Cisplatin injection (3mg/kg caused a significant increase in kaolin consumption, which was indicated by increased carmine dye excretion in faeces compared to control. Pre-treatment with HAT and ondansetron significantly suppressed kaolin consumption induced by Cisplatin. The present findings showed that the exact kaolin consumption can be quantified by measuring the faecal excretion of carmine, which was added in kaolin pellets and this can be a sensitive model to study the anti-emetic potential of drugs, overcoming the inherent disadvantages of measuring direct kaolin intake. Pre-treatment with ondansetron and HAT significantly decreased kaolin consumption in rats-induced by Cisplatin injection, which was further shown by decrease in faecal excretion of carmine, indicating anti-emetic potential of tested drugs.

  15. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    Science.gov (United States)

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  16. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China); Xia, Qiang, E-mail: xiaqiang1@yahoo.com.cn [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  17. Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.

    Directory of Open Access Journals (Sweden)

    Mariana Yasue Saito Miyagi

    Full Text Available Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI. In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX. The group submitted to exercise before cisplatin administration (CIS-EX exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS. Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.

  18. Histological and histochemical study on the protective effect of WR -2721 against cisplatin-induced nephrotoxicity in gamma irradiated female albino rats

    International Nuclear Information System (INIS)

    Cisplatin is a highly effective antineoplastic drug used against several types of human cancers. however, nephrotoxicity is one of the most important side-effects of cisplatin therapy. the present study investigates the protective effect of a synthetic radioprotector, namely WR-2721 (amifostine) against cisplatin -induced nephrotoxicity in gamma-irradiated female rats. 48 female rats were divided into eight groups each of 6 rats: 1-control, 2-injected i.p. with WR-2721 alone at a dose of 100 mg/kg body wt daily for 5 days. 3-irradiated with gamma rays (7.5 Gy) at fractionated doses each of 1.5 Gy daily for 5 days . 4 -injected with cisplatin (2.5 mg/kg body wt ) daily for 5 days. 5 -irradiated with gamma rays daily (as group 3) 1/2 h before cisplatin injection (as group 4). 6-injected with wr- 2721 (as group 2) 1/2 h prior to gamma -irradiation . 7-injected with WR-2721 (as group 2) one h prior to cisplatin injection . group 8 injected with WR-2721 (as group 2) prior to combined treatment with both gamma -irradiation and cisplatin. WR-2721 displayed slight protective effect against the adverse effects of gamma -irradiation in the kidney of female rate. the obtained results exhibited weak protective effect for WR-2721 against cisplatin-induced histopathological changes in the kidney of gamma-irradiated female rats. the histochemical data showed that WR-2721 administration slightly stabilizing the succinic dehydrogenase and acid phosphatase enzymes in the kidney of gamma -radiated female rats

  19. Cisplatin Induces Overactivation of the Dormant Primordial Follicle through PTEN/AKT/FOXO3a Pathway which Leads to Loss of Ovarian Reserve in Mice.

    Directory of Open Access Journals (Sweden)

    Eun Mi Chang

    Full Text Available Cisplatin is a first-line chemotherapeutic agent for ovarian cancer that acts by promoting DNA cross links and adduct. However drug resistance and considerable side effects including reproductive toxicity remain a significant challenge. PTEN is well known as a tumor suppressor function which plays a fundamental role in the regulation of the cell cycle, apoptosis and development of cancer. At the same time PTEN has been revealed to be critically important for the maintenance of the primordial follicle pool. In this study, we investigated the role of PTEN/Akt/FOXO3 pathway in cisplatin-induced primordial follicle depletion. Cisplatin induced ovarian failure mouse model was used to evaluate how this pathway involves. In vitro maturation was used for oocyte rescue after cisplatin damage. We found that cisplatin treatment decreased PTEN levels, leading to a subsequent increase in the phosphorylation of key molecules in the pathway. The activation of the PTEN/Akt/FOXO3 pathway cascade increased cytoplasmic translocation of FOXO3a in cisplatin-treated follicles, which in turn increased the pool size of growing follicles, and rapidly depleted the number of dormant follicles. Once activated, the follicles were more prone to apoptosis, and their cumulus cells showed a loss of luteinizing hormone (LH receptor expression, which leads to failure during final maturation and ovulation. In vitro maturation to rescue oocytes in a cisplatin-treated mouse model resulted in successful maturation and fertilization. This study is the first to show the involvement of the PTEN/Akt/FOXO3 pathway in premature ovarian failure after cisplatin treatment and the possibility of rescue through in vitro maturation.

  20. Local cooling does not prevent hyperalgesia following burn injury in humans

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Pedersen, Juri L;

    2002-01-01

    -inflammatory or anti-hyperalgesic potential of early cooling after thermal injury. Twenty-four healthy volunteers participated in this randomized, single-blinded study. Following baseline measurements, which included inflammatory variables (skin temperature, erythema index) and sensory variables (thermal and...... the burns. One of the thermodes cooled the burn (8 degrees C for 30 min) whereas the other thermode was a non-active dummy on the control burn. Inflammatory and sensory variables were followed for 160 min after end of the cooling procedure. The burn injury induced significant increases in skin...... temperature (P<0.0005), erythema index (P<0.0001), thermal pain responses (P<0.0005), mechanical pain responses (P<0.005) and secondary hyperalgesia, and significant decreases in heat pain threshold (P<0.0005) and mechanical pain threshold (P<0.0005). There were no post-cooling effects on skin temperature (P...

  1. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

    Directory of Open Access Journals (Sweden)

    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  2. Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury?

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Werner, Mads U; Ringsted, Thomas K; Rowbotham, Michael C; Taylor, Bradley K; Dahl, Joergen B

    2013-01-01

    Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, h......, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury....

  3. Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor ε subunit knockout mice

    OpenAIRE

    Minami, Toshiaki; Sugatani, Junko; Sakimura, Kenji; Abe, Manabu; Mishina, Masayoshi; Ito, Seiji

    1997-01-01

    We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice lacking NMDA receptor ε1, ε4, or ε1/ε4 subunits.PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg−1 in wild-type mice. But PGE2 could not induce hyperalgesia in ε1...

  4. Sip-jeon-dea-bo-tang, a traditional herbal medicine, ameliorates cisplatin-induced anorexia via the activation of JAK1/STAT3-mediated leptin and IL-6 production in the fat tissue of mice.

    Science.gov (United States)

    Woo, Sang-Mi; Choi, Youn Kyung; Kim, Ah-Jeong; Yun, Yee Jin; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong Gyu

    2016-04-01

    Despite its therapeutic advantages, chemotherapy can also cause adverse effects, including anorexia and loss of appetite. Although numerous patients with cancer have been reported to suffer from anorexia during or following chemotherapy, treatment options for anorexia remain to be determined. In Asian countries, traditional medicines are widely used to treat problems with appetite; sip-jeon-dea-bo-tang (SJDBT) is one of those medicines used for the treatment of anorexia. The present study demonstrated that SJDBT ameliorated cisplatin-induced anorexia. In a mouse model of chemotherapy-induced anorexia, oral administration of SJDBT prevented the cisplatin-induced reduction of food intake, inhibiting weight loss. The results of multiplex assays showed that SJDBT only altered the levels of interleukin (IL)-6 and leptin in the serum and fat tissue. In addition, SJDBT maintained the serum leptin level and increased the serum IL-6 level, whereas cisplatin reduced the levels of both serum leptin and IL‑6. Furthermore, SJDBT was revealed to increase the levels of leptin and IL-6 in the fat tissue by activating the JAK1/STAT3 signaling pathway. In conclusion, the present results revealed that SJDBT ameliorated cisplatin-induced anorexia, suggesting its usefulness in the prevention of anorexia during chemotherapy. PMID:26936678

  5. Constitutively active ErbB2 regulates cisplatin-induced cell death in breast cancer cells via pro- and antiapoptotic mechanisms

    DEFF Research Database (Denmark)

    Sigurðsson, Haraldur H; Olesen, Christina Wilkens; Dybboe, Rie;

    2015-01-01

    UNLABELLED: Despite the frequent expression of N-terminally truncated ErbB2 (ΔNErbB2/p95HER2) in breast cancer and its association with Herceptin resistance and poor prognosis, it remains poorly understood how ΔNErbB2 affects chemotherapy-induced cell death. Previously it was shown that ΔNErbB2...... upregulates acid extrusion from MCF-7 breast cancer cells and that inhibition of the Na(+)/H(+) exchanger (SLC9A1/NHE1) strongly sensitizes ΔNErbB2-expressing MCF-7 cells to cisplatin chemotherapy. The aim of this study was to identify the mechanism through which ΔNErbB2 regulates cisplatin-induced breast...... cancer cell death, and determine how NHE1 regulates this process. Cisplatin treatment elicited apoptosis, ATM phosphorylation, upregulation of p53, Noxa (PMAIP1), and PUMA (BBC3), and cleavage of caspase-9, -7, fodrin, and PARP-1 in MCF-7 cells. Inducible ΔNErbB2 expression strongly reduced cisplatin...

  6. Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Satoshi Tanida

    2012-01-01

    Full Text Available Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c-Myc suppresses bridging integrator 1 (BIN1, thereby releasing poly(ADP-ribosepolymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity.

  7. Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer.

    Science.gov (United States)

    Ye, Zhiqiang; Hao, Rutian; Cai, Yefeng; Wang, Xiaobo; Huang, Guanli

    2016-04-01

    Accumulating evidence shows that microRNAs (miRNAs) have a critical role in the initiation and progression of types of human cancer, including breast cancer. Recent research indicated that miRNAs are also related with the chemotherapy on cancers. In this study, the expression of miR-221 in breast cancer (BC) patients' serum and cancer tissues was found to be significantly up-regulated. The results of in vitro MTT assay indicated that although the anti-miR-221 oligonucleotide alone did not influence the viability of BC cell lines markedly, it significantly promoted the cytotoxicity of cisplatin (DDP) to BC cells. Mechanistic studies demonstrated that the gene of BIM (Bcl-2 interacting mediator of cell death), a pro-apoptotic Bcl-2 family protein, was up-regulated by the knockdown of miR-221. We found that the synergetic effect of anti-miR-221 on increasing the sensitivity of MDA-MB-231 was BIM dependant. Furthermore, results of immunoprecipitation showed the up-regulated BIM directly combined with the Bax and Bak, leading to mitochondrial dysfunction. Our results suggest the anti-miR-221 could promote the cisplatin-inducing apoptosis by targeting the Bim-Bax/Bak axis in breast cancer. PMID:26503209

  8. Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia.

    Science.gov (United States)

    Song, X J; Hu, S J; Greenquist, K W; Zhang, J M; LaMotte, R H

    1999-12-01

    Chronic compression of the dorsal root ganglion (CCD) was produced in adult rats by implanting a stainless steel rod unilaterally into the intervertebral foramen, one rod at L(4) and another at L(5). Two additional groups of rats received either a sham surgery or an acute injury consisting of a transient compression of the ganglion. Withdrawal of the hindpaw was used as evidence of a nocifensive response to mechanical and thermal stimulation of the plantar surface. In addition, extracellular electrophysiological recordings of spontaneous discharges were obtained from dorsal root fibers of formerly compressed ganglia using an in vitro nerve-DRG-dorsal root preparation. The mean threshold force of punctate indentation and the mean threshold temperature of heating required to elicit a 50% incidence of foot withdrawal ipsilateral to the CCD were significantly lower than preoperative values throughout the 35 days of postoperative testing. The number of foot withdrawals ipsilateral to the CCD during a 20-min contact with a temperature-controlled floor was significantly increased over preoperative values throughout postoperative testing when the floor was 4 degrees C (hyperalgesia) and, to a lesser extent, when it was 30 degrees C (spontaneous pain). Stroking the foot with a cotton wisp never elicited a reflex withdrawal before surgery but did so in most rats tested ipsilateral to the CCD during the first 2 postoperative weeks. In contrast, the CCD produced no changes in responses to mechanical or thermal stimuli on the contralateral foot. The sham operation and acute injury produced no change in behavior other than slight, mechanical hyperalgesia for approximately 1 day, ipsilateral to the acute injury. Ectopic spontaneous discharges generated within the chronically compressed ganglion and, occurring in the absence of blood-borne chemicals and without an intact sympathetic nervous system, were recorded from neurons with intact, conducting, myelinated or unmyelinated

  9. Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

    OpenAIRE

    Yokoyama, Takeshi; Lisi, Tammy L.; Moore, Steven A.; Sluka, Kathleen A.

    2007-01-01

    Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 µL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were ...

  10. Complications of sodium hydroxide chemical matrixectomy: nail dystrophy, allodynia, hyperalgesia.

    Science.gov (United States)

    Bostancı, Seher; Koçyiğit, Pelin; Güngör, Hilayda Karakök; Parlak, Nehir

    2014-11-01

    Ingrown toenails are seen most commonly in young adults, and they can seriously affect daily life. Partial nail avulsion with chemical matrixectomy, generally by using either sodium hydroxide or phenol, is one of the most effective treatment methods. Known complications of phenol matrixectomy are unpredictable tissue damage, prolonged postoperative drainage, increased secondary infection rates, periostitis, and poor cosmetic results. To our knowledge, there have been no reports about the complications related to sodium hydroxide matrixectomy. Herein, we describe three patients who developed nail dystrophy, allodynia, and hyperalgesia after sodium hydroxide matrixectomy. PMID:25514278

  11. Irritable bowel syndrome: a test of the colonic hyperalgesia hypothesis.

    Science.gov (United States)

    Latimer, P; Campbell, D; Latimer, M; Sarna, S; Daniel, E; Waterfall, W

    1979-09-01

    This study tested the hypothesis that, patients with irritable bowel syndrome (IBS), there is a primary hyperalgesia of the colon. Previous work, which examined these patients and normals, has not included subjects who provide a control for relevant psychological characteristics. We compared ratings of pain, following varying degrees of distension of the sigmoid colon, in normals, patients with IBS, and patients who were psychologically disturbed but without bowel symptoms. Psychological characteristics were assessed by a psychiatric interview and psychometric inventories; response to distension was tested by placing a tube in the rectosigmoid colon and successively inflating a nd deflating a balloon at its tip at 10 cm3 increments up to 50 cm3. Ratings of pain were recorded at each volume. The results indicated that the two patient groups were psychologically similar and both were more disturbed than normals. A linear relation was found between reports of pain and volume of distension in all three groups. There were no significant differences between the proportions of subjects experiencing pain in each group or the average of the ratings. There were no significant associations between the pain ratings and measures of anxiety, depression, neuroticism, and extraversion. The data do not support the hypothesis that colonic hyperalgesia is an important contributory factor in the etiology of the irritable bowel syndrome. PMID:537039

  12. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

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    Yoshio Terada

    Full Text Available BACKGROUND/AIMS: Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI. METHOD: We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post. RESULT: CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. CONCLUSION: These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  13. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: liutaomedical@qq.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Guo, Xinjin, E-mail: guo.xinjin@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); and others

    2012-11-01

    The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.

  14. Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats.

    Science.gov (United States)

    Hagar, Hanan; Medany, Azza El; Salam, Reem; Medany, Gamila El; Nayal, Omina A

    2015-02-01

    Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250 mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity. PMID:25488130

  15. Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

    Science.gov (United States)

    Al-Husseiny, Fatma; Sobh, Mohamed Ahmed; Ashour, Rehab H.; Foud, Samah; Medhat, Tarek; El-Gilany, Abdel-Hady; Elghannam, Doaa; Abdel-Ghaffar, Hassan; Saad, Mohamed-Ahdy; Sobh, Mohamed

    2016-01-01

    Background and objectives Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. Methods 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. Results hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. Conclusion hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity. PMID:27426088

  16. Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

    Science.gov (United States)

    Jia, Yanfei; Sun, Haiji; Wu, Hongqiao; Zhang, Huilin; Zhang, Xiuping; Xiao, Dongjie; Ma, Xiaoli; Wang, Yunshan

    2016-01-01

    Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin. PMID:26909550

  17. ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.

    Science.gov (United States)

    Gregory, Nicholas S; Brito, Renan G; Fusaro, Maria Cláudia G Oliveira; Sluka, Kathleen A

    2016-03-01

    An acute bout of exercise can exacerbate pain, hindering participation in regular exercise and daily activities. The mechanisms underlying pain in response to acute exercise are poorly understood. We hypothesized that proton accumulation during muscle fatigue activates acid-sensing ion channel 3 (ASIC3) on muscle nociceptors to produce hyperalgesia. We investigated the role of ASIC3 using genetic and pharmacological approaches in a model of fatigue-enhanced hyperalgesia. This model uses two injections of pH 5.0 saline into muscle in combination with an electrically induced fatigue of the same muscle just prior to the second injection of acid to induce mechanical hyperalgesia. We show a significant decrease in muscle force and decrease in muscle pH after 6 min of electrical stimulation. Genetic deletion of ASIC3 using knockout mice and pharmacological blockade of ASIC3 with APETx2 in muscle prevents the fatigue-enhanced hyperalgesia. However, ASIC3(-/-) mice and APETx2 have no effect on the fatigue response. Genetic deletion of ASIC3 in primary afferents innervating muscle using an HSV-1 expressing microRNA (miRNA) to ASIC3 surprisingly had no effect on the development of the hyperalgesia. Muscle fatigue increased the number of macrophages in muscle, and removal of macrophages from muscle with clodronate liposomes prevented the development of fatigue-enhanced hyperalgesia. Thus, these data suggest that fatigue reduces pH in muscle that subsequently activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult. PMID:25577172

  18. Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells.

    Science.gov (United States)

    Matsumoto, Masaru; Nakajima, Wataru; Seike, Masahiro; Gemma, Akihiko; Tanaka, Nobuyuki

    2016-04-29

    Cisplatin is a highly effective anticancer drug for treatment of various tumors including non-small-cell lung cancer (NSCLC), and is especially useful in cases nonresponsive to molecular-targeted drugs. Accumulating evidence has shown that cisplatin activates the p53-dependent apoptotic pathway, but it also induces apoptosis in p53-mutated cancer cells. Here we demonstrated that DNA-damage inducible proapoptotic BH3 (Bcl-2 homology region 3)-only Bcl-2 family members, Noxa, Puma, Bim and Bid, are not involved in cisplatin-induced apoptosis in human NSCLC cell lines. In contrast, the expression of proapoptotic multidomain Bcl-2-family members, Bak and Bax, was induced by cisplatin in p53-dependent and -independent manners, respectively. Moreover, in wild-type p53-expressing cells, cisplatin mainly used the Bak-dependent apoptotic pathway, but this apoptotic pathway shifted to the Bax-dependent pathway by loss-of-function of p53. Furthermore, both Bak- and Bax-induced apoptosis was enhanced by the antiapoptotic Bcl-2 family member, Bcl-XL knockdown, but not by Mcl-1 knockdown. From this result, we tested the effect of ABT-263 (Navitoclax), the specific inhibitor of Bcl-2 and Bcl-XL, but not Mcl-1, and found that ABT-263 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells in the presence or absence of p53. These results indicate a novel regulatory system in cisplatin-induced NSCLC cell apoptosis, and a candidate efficient combination chemotherapy method against lung cancers. PMID:26996126

  19. Bromoenol Lactone, an Inhibitor of Calcium-Independent Phospholipase A2, Suppresses Carrageenan-Induced Prostaglandin Production and Hyperalgesia in Rat Hind Paw

    Science.gov (United States)

    Tsuchida, Keiichiro; Ibuki, Takae; Matsumura, Kiyoshi

    2015-01-01

    Prostaglandin (PG) E2 and PGI2 are essential to hyperalgesia in inflammatory tissues. These prostaglandins are produced from arachidonic acid, which is cleaved from membrane phospholipids by the action of phospholipase A2 (PLA2). Which isozyme of PLA2 is responsible for the cleavage of arachidonic acid and the production of prostaglandins essential to inflammation-induced hyperalgesia is not clear. In this study, we examined the effects of two PLA2 isozyme-specific inhibitors on carrageenan-induced production of PGE2 and PGI2 in rat hind paw and behavioral nociceptive response to radiant heat. Local administration of bromoenol lactone (BEL), an inhibitor of calcium-independent PLA2 (iPLA2), significantly reduced carrageenan-induced elevation of prostaglandins in the inflamed foot pad 3 h after injection. It also ameliorated the hyperalgesic response between 1 h and 3 h after carrageenan injection. On the other hand, AACOCF3, an inhibitor of cytosolic PLA2, suppressed neither prostaglandin production nor the hyperalgesic response. BEL did not suppress the mRNA levels of iPLA2β, iPLA2γ, cyclooxygenase-2, microsomal prostaglandin E synthase, prostaglandin I synthase, or proinflammatory cytokines in the inflamed foot pad, indicating that BEL did not suppress inflammation itself. These results suggest that iPLA2 is involved in the production of prostaglandins and hyperalgesia at the inflammatory loci. PMID:26063975

  20. Lipopolysaccharide-induced hyperalgesia of intracranial capsaicin sensitive afferents in conscious rats

    NARCIS (Netherlands)

    Kemper, RHA; Spoelstra, MB; Meijler, WJ; Ter Horst, GJ

    1998-01-01

    Migraineous and non-migraineous headache is reported to be at highest intensity after an infection. This study investigated whether activation of the immune system can induce hyperalgesia in intracranial capsaicin sensitive afferents. The effects of intraperitoneal injected lipopolysaccharides (LPS)

  1. Descending facilitatory pathways from the RVM initiate and maintain bilateral hyperalgesia after muscle insult

    OpenAIRE

    Tillu, DV; Gebhart, GF; Sluka, KA

    2007-01-01

    The rostral ventromedial medulla (RVM) is involved in facilitation of spinal nociceptive processing and generation of hyperalgesia in inflammatory and neuropathic pain models. We hypothesized that the bilateral hyperalgesia that develops after repeated intramuscular injections of acidic saline is initiated and maintained by activation of descending facilitatory pathways from the RVM. Male Sprague-Dawley rats were implanted with intracerebral guide cannulae into the nucleus raphe magnus (NRM) ...

  2. Cyclosporin inhibits hyperalgesia and edema in arthritic rats: role of the central nervous system

    Directory of Open Access Journals (Sweden)

    Francischi J.N.

    1997-01-01

    Full Text Available Since arthritis induced by Mycobacterium products (adjuvant in rats is considered to be immunologically driven, the objective of the present study was to determine if the immunosuppressor drug cyclosporin could affect hindpaw edema and joint hyperalgesia simultaneously. Female Holtzman rats (140-170 g presented hyperalgesia and edema on the 8th and 12th day following adjuvant injection. Daily systemic (oral or intramuscular administration of cyclosporin (0.5-5.0 mg kg-1 day-1 or dexamethasone (0.01-0.1 mg kg-1 day-1 for 15 days starting on day zero dose-dependently inhibited the hindpaw edema and hyperalgesia in arthritic rats. However, hyperalgesia but not edema could be detected two days after cyclosporin withdrawal. We concluded that a the continuous presence of cyclosporin is essential to reduce the development of joint hyperalgesia and that b different mechanisms underlie the appearance of hyperalgesia and edema in this model. The intracerebroventricular (icv administration of 5-50-fold smaller doses of cyclosporin (1.5-150 µg/day or dexamethasone (15 µg/day also reduced the arthritic hindpaw edema and hyperalgesia. Peripheral blood from animals injected with effective systemic cyclosporin doses showed detectable levels of the drug, whereas peripheral blood from those injected with icv cyclosporin did not, as measured by specific RIA. Our results indicate that cyclosporin administered by the central route is as effective as by the systemic route to reduce joint hyperalgesia and hindpaw edema in arthritic rats. The antiarthritic effect induced by low doses of cyclosporin in the central nervous system (CNS could be explored to avoid its often associated systemic side effects during chronic therapy. However, the mechanism(s involved in the antiarthritic response to cyclosporin in the CNS remain to be elucidated

  3. Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

    Science.gov (United States)

    Ferrari, L F; Levine, J D; Green, P G

    2016-03-11

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. PMID:26779834

  4. Morphine Induces Hyperalgesia without Involvement of μ-Opioid Receptor or Morphine-3-glucuronide

    OpenAIRE

    Swartjes, Maarten; Mooren, René A G; Waxman, Amanda R.; Arout, Caroline; van de Wetering, Koen; den Hartigh, Jan; Beijnen, Jos H.; Kest, Benjamin; Dahan, Albert

    2012-01-01

    Opioid-induced hyperalgesia (OIH) is a paradoxical increase in pain perception that may manifest during opioid treatment. For morphine, the metabolite morphine-3-glucuronide (M3G) is commonly believed to underlie this phenomenon. Here, in three separate studies, we empirically assess the role of M3G in morphine-induced hyperalgesia. In the first study, CD-1 mice injected with morphine (15 mg/kg subcutaneously) after pretreatment with the opioid receptor antagonist naltrexone (NTX) (15 mg/kg) ...

  5. Activation of β-catenin by inhibitors of glycogen synthase kinase-3 ameliorates cisplatin-induced cytotoxicity and pro-inflammatory cytokine expression in HEI-OC1 cells

    International Nuclear Information System (INIS)

    Graphical abstract: - Abstract: Cisplatin is used in the treatment of a wide variety of solid tumors, but its use is limited by its serious adverse effects, including ototoxicity. Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase that regulates a variety of cellular functions by phosphorylating its substrates. However, the otoprotective effect of GSK-3 inhibitors is poorly understood. Here, we investigated whether GSK-3 is involved in cisplatin-induced ototoxicity in HEI-OC1 cells and organs of Corti (OCs). GSK-3 inhibitors suppressed cisplatin-induced apoptosis determined by decreased p53 activity, and also decreased expression of PARP and p53 target genes such as p21 and PUMA. The effect of GSK-3 inhibitors was mediated by markedly increased nuclear β-catenin that in turn blocked nuclear translocation of NF-κB. siRNA-mediated β-catenin knockdown markedly increased the expression of NF-κB target genes, such as TNF-α and IL-6. Our data suggest that the GSK-3/β-catenin pathway may play a central role in cisplatin-mediated cytotoxicity in HEI-OC1 cells and hair cells of OCs in vitro

  6. Cisplatin induced paroxysmal supraventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Waseem Raja

    2013-01-01

    Full Text Available Cisplatin or cis-diamminedichloroplatinum (CDDP is the first member of a class of platinum-containing anti-cancer drugs that act by binding to and causing cross-linking of deoxyribonucleic acid, which ultimately triggers apoptosis. Cisplatin has a broad-spectrum antineoplastic activity against various types of human tumors. Unfortunately, the optimal usefulness of Cisplatin is limited secondary to its dose related toxicity especially nephrotoxicity. Cisplatin chemotherapy is also associated with cardiotoxic effects that may range from silent arrhythmias to heart failure and even sudden cardiac death. These effects are more pronounced when cisplatin is combined with other cardiotoxic drugs. Here, we report a case of patient of cancer lung who developed paroxysmal supraventricular tachycardia following administration of Cisplatin. A brief review of the literature follows.

  7. Cisplatin induced paroxysmal supraventricular tachycardia

    OpenAIRE

    Waseem Raja; M Hussain Mir; Imtiyaz Dar; Muzamil Ahmad Banday; Irfan Ahmad

    2013-01-01

    Cisplatin or cis-diamminedichloroplatinum (CDDP) is the first member of a class of platinum-containing anti-cancer drugs that act by binding to and causing cross-linking of deoxyribonucleic acid, which ultimately triggers apoptosis. Cisplatin has a broad-spectrum antineoplastic activity against various types of human tumors. Unfortunately, the optimal usefulness of Cisplatin is limited secondary to its dose related toxicity especially nephrotoxicity. Cisplatin chemotherapy is also associated ...

  8. Model of Hyperalgesia Associated with Lameness in Dairy Cattle

    Directory of Open Access Journals (Sweden)

    M.A. Aba

    2006-01-01

    Full Text Available The nociceptive response was evaluated in dairy cattle after injection of a solution of formalin (4% in the the external claw hoof. The nociceptive response in cows exhibited a biphasic time course behavior to pain stimulus similar to the one described in trials of formalin test in different laboratory animals. The cortisol plasma concentration after injections of formalin was high during the two phases of the pain response showing a correspondence with clinical nociceptive behaviors. The 4 % formalin injections in claw hoof in cows can be used to evaluate the possible mechanisms of anti-nociceptive drugs of central and peripheral actions. Besides, it is a reversible model; it does not need complicated equipment and it is simple to be carried out by personnel with certain experience in cow lameness. This nociceptive model might be useful to research the therapeutic role of analgesic and anti-inflammatory drugs of short half life in the modulation of hyperalgesia associated with lameness in dairy cattle.

  9. TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation

    OpenAIRE

    Walder, Roxanne Y.; Radhakrishnan, Rajan; Loo, Lipin; Rasmussen, Lynn A.; Mohapatra, Durga P.; Wilson, Steven P.; SLUKA, KATHLEEN A.

    2012-01-01

    Inflammatory thermal hyperalgesia is principally mediated through transient receptor potential vanilloid 1 (TRPV1) channels, as demonstrated by prior studies using models of cutaneous inflammation. Muscle pain is significantly different from cutaneous pain, and the involvement of TRPV1 in hyperalgesia induced by muscle inflammation is unknown. We tested whether TRPV1 contributes to the development of mechanical and heat hypersensitivity of the paw in TRPV1−/− mice after muscle inflammation. B...

  10. Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

    Science.gov (United States)

    Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung

    2014-01-01

    Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699

  11. Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars;

    2000-01-01

    We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P < 0.001), whereas ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine...

  12. Secondary Hyperalgesia Phenotypes Exhibit Differences in Brain Activation during Noxious Stimulation

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke; Mårtensson, Johan; Larsson, Henrik B W; Dahl, Jørgen Berg

    2015-01-01

    the burn-injury) (p < 0.05). After the burn-injury, we found significant differences between responders during noxious stimulation of both primary (p < 0.01) and secondary hyperalgesia (p ≤ 0.04) skin areas. A decreased volume of the right (p = 0.001) and left caudate nucleus (p = 0.01) was detected....... To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47°C, 7...... hyperalgesia areas after burn-injury. In addition, T1-weighted images were used to measure differences in gray-matter density in cortical and subcortical regions of the brain. We found significant differences in neuronal activity between high- and low-sensitization responders at baseline (before application of...

  13. Serotonin Receptor 2B Mediates Mechanical Hyperalgesia by Regulating Transient Receptor Potential Vanilloid 1.

    Science.gov (United States)

    Su, Yeu-Shiuan; Chiu, Yuan-Yi; Lin, Shih-Yuan; Chen, Chih-Cheng; Sun, Wei-Hsin

    2016-05-01

    Serotonin [5-hydroxytryptamine (5-HT)], an inflammatory mediator, contributes to inflammatory pain. The presence of multiple 5-HT subtype receptors on peripheral and central nociceptors complicates the role of 5-HT in pain. Previously, we found that 5-HT2B/2C antagonist could block 5-HT-induced mechanical hyperalgesia. However, the types of neurons or circuits underlying this effect remained unsolved. Here, we demonstrate that the Gq/11-phospholipase Cβ-protein kinase Cε (PKCε) pathway mediated by 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia in mice. Administration of a transient receptor potential vanilloid 1 (TRPV1) antagonist inhibited the 5-HT-induced mechanical hyperalgesia. 5-HT injection enhanced 5-HT- and capsaicin-evoked calcium signals specifically in isolectin B4 (IB4)-negative neurons; signals were inhibited by a 5-HT2B/2C antagonist and PKCε blocker. Thus, 5-HT2B mediates 5-HT-induced mechanical hyperalgesia by regulating TRPV1 function. PMID:26635025

  14. ASICs Do Not Play a Role in Maintaining Hyperalgesia Induced by Repeated Intramuscular Acid Injections

    Directory of Open Access Journals (Sweden)

    Mamta Gautam

    2012-01-01

    Full Text Available Repeated intramuscular acid injections produce long-lasting mechanical hyperalgesia that depends on activation of ASICs. The present study investigated if pH-activated currents in sensory neurons innervating muscle were altered in response to repeated acid injections, and if blockade of ASICs reverses existing hyperalgesia. In muscle sensory neurons, the mean acid-evoked current amplitudes and the biophysical properties of the ASIC-like currents were unchanged following acidic saline injections when compared to neutral pH saline injections or uninjected controls. Moreover, increased mechanical sensitivity of the muscle and paw after the second acid injection was unaffected by local blockade of ASICs (A-317567 in the muscle. As a control, electron microscopic analysis showed that the tibial nerve was undamaged after acid injections. Our previous studies demonstrated that ASICs are important in the development of hyperalgesia to repeated acid injections. However, the current data suggest that ASICs are not involved in maintaining hyperalgesia to repeated intramuscular acid injections.

  15. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration?

    DEFF Research Database (Denmark)

    Sjøgren, P; Thunedborg, L P; Christrup, Lona Louring;

    1998-01-01

    Recently, clinical reports have suggested a relationship between the occurrence of hyperalgesia, allodynia and/or myoclonus and treatment with high doses of morphine in humans. Although few clinical descriptions of these phenomena are available, experimental work supports the notion that high dos...

  16. Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

    Directory of Open Access Journals (Sweden)

    Picolo G.

    2002-01-01

    Full Text Available Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom. The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation.

  17. Hyperalgesia in an immobilized rat hindlimb: effect of treadmill exercise using non-immobilized limbs.

    Science.gov (United States)

    Chuganji, Sayaka; Nakano, Jiro; Sekino, Yuki; Hamaue, Yohei; Sakamoto, Junya; Okita, Minoru

    2015-01-01

    Cast immobilization of limbs causes hyperalgesia, which is a decline of the threshold of mechanical and thermal mechanical stimuli. The immobilization-induced hyperalgesia (IIH) can disturb rehabilitation and activities of daily living in patients with orthopedic disorders. However, it is unclear what therapeutic and preventive approaches can be used to alleviate IIH. Exercise that activates the descending pain modulatory system may be effective for IIH. The purpose of this study was to investigate the effects of treadmill exercise during the immobilization period, using the non-immobilized limbs, on IIH. Thirty-six 8-week-old Wistar rats were randomly divided into (1) control, (2) immobilization (Im), and (3) immobilization and treadmill exercise (Im+Ex) groups. In the Im and Im+Ex groups, the right ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for an 8-week period. In the Im+Ex group, treadmill exercise (15 m/min, 30 min/day, 5 days/week) was administered during the immobilization period while the right hindlimb was kept immobilized. Mechanical hyperalgesia was measured using von Frey filaments every week. To investigate possible activation of the descending pain modulatory system, beta-endorphin expression levels in hypothalamus and midbrain periaqueductal gray were analyzed. Although IIH clearly occurred in the Im group, the hyperalgesia was partially but significantly reduced in the Im+Ex group. Beta-endorphin, which is one of the endogenous opioids, was selectively increased in the hypothalamus and midbrain periaqueductal gray of the Im+Ex group. Our data suggest that treadmill running using the non-immobilized limbs reduces the amount of hyperalgesia induced in the immobilized limb even if it is not freed. This ameliorating effect might be due to the descending pain modulatory system being activated by upregulation of beta-endorphin in the brain. PMID:25304541

  18. Two-week cast immobilization induced chronic widespread hyperalgesia in rats.

    Science.gov (United States)

    Ohmichi, Y; Sato, J; Ohmichi, M; Sakurai, H; Yoshimoto, T; Morimoto, A; Hashimoto, T; Eguchi, K; Nishihara, M; Arai, Y-C P; Ohishi, H; Asamoto, K; Ushida, T; Nakano, T; Kumazawa, T

    2012-03-01

    It has been postulated that physical immobilization is an essential factor in developing chronic pain after trauma or surgery in an extremity. However, the mechanisms of sustained immobilization-induced chronic pain remain poorly understood. The present study, therefore, aimed to develop a rat model for chronic post-cast pain (CPCP) and to clarify the mechanism(s) underlying CPCP. To investigate the effects of cast immobilization on pain behaviours in rats, one hindlimb was immobilized for 2 weeks with a cast and remobilization was conducted for 10 weeks. Cast immobilization induced muscle atrophy and inflammatory changes in the immobilized hindlimb that began 2 h after cast removal and continued for 1 week. Spontaneous pain-related behaviours (licking and reduction in weight bearing) in the immobilized hindlimb were observed for 2 weeks, and widespread mechanical hyperalgesia in bilateral calves, hindpaws and tail all continued for 5-10 weeks after cast removal. A sciatic nerve block with lidocaine 24 h after cast removal transitorily abolished bilateral mechanical hyperalgesia in CPCP rats, suggesting that sensory inputs originating in the immobilized hindlimb contribute to the mechanism of both ipsilateral and contralateral hyperalgesia. Intraperitoneal injection of the free radical scavengers 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxy1 or N-acetylcysteine 24 h after cast removal clearly inhibited mechanical hyperalgesia in bilateral calves and hindpaws in CPCP rats. These results suggest that cast immobilization induces ischaemia/reperfusion injury in the hindlimb and consequent production of oxygen free radicals, which may be involved in the mechanism of widespread hyperalgesia in CPCP rats. PMID:22337282

  19. Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and morphine-induced hyperalgesia

    Directory of Open Access Journals (Sweden)

    Chen J

    2012-11-01

    Full Text Available Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2 DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated. Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage

  20. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng.

    Science.gov (United States)

    Yousef, Mokhtar I; Hussien, Hend M

    2015-04-01

    Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes. PMID:25640527

  1. Effect of Intraperitoneal Administered Ginseng Total Saponins on Hyperalgesia Induced by Repeated Intramuscular Injection of Acidic Saline in Rats

    OpenAIRE

    Kim, Won Joong; Kang, Hyun; Kim, Jung Eun; Choi, Geun Joo; Shin, Hwa Yong; Baek, Chong Wha; Jung, Yong Hun; Woo, Young Choel; Kim, Su Hyun; Lee, Jeong Hyuk

    2014-01-01

    The aim of this study was to assess the antinociceptive activity of ginseng total saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of acidic saline in rats and to examine the mechanisms involved. Rats were injected intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal threshold (MWT) was ass...

  2. Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

    Institute of Scientific and Technical Information of China (English)

    Tao Yi; Li Qi; Huangan Wu; Xiaopeng Ma; Huirong Liu; Xiaomei Wang

    2012-01-01

    Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu (ST25) and Shangjuxu (ST37) once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

  3. Experimental knee pain evoke spreading hyperalgesia and facilitated temporal summation of pain

    DEFF Research Database (Denmark)

    Jørgensen, Tanja Schjødt; Henriksen, Marius; Danneskiold-Samsøe, Bente; Bliddal, Henning; Graven-Nielsen, Thomas

    2013-01-01

    was induced in the infrapatellar fat pad by injection of hypertonic saline and the contralateral infrapatellar fat pad was injected with isotonic saline as control. OUTCOME MEASURES: Pressure pain thresholds, temporal summation of pressure pain, and cutaneous mechanosensitivity were assessed on three...... sensitivity. The study showed that acute knee joint pain leads to hyperalgesia and facilitated temporal summation in the infrapatellar fat pad and in muscles located distant to the injection site, in subjects with no history of knee pain....... occasions: baseline, immediately after the injection, and when pain had vanished. Assessments sites were located in the peripatellar region, vastus lateralis, and tibialis anterior muscles. RESULTS: The experimental knee pain model demonstrated 1) hyperalgesia to pressure stimulation on the infrapatellar...

  4. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

    Directory of Open Access Journals (Sweden)

    Huynh Truc

    2007-12-01

    Full Text Available Abstract Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18 that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

  5. Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury

    DEFF Research Database (Denmark)

    Pedersen, J L; Crawford, M E; Dahl, J B;

    1996-01-01

    whether a prolonged nerve block administered before a superficial burn injury could reduce local inflammation and late hyperalgesia after recovery from the block. METHODS: The effects of a preemptive saphenous nerve block on primary and secondary hyperalgesia, skin erythema, and blister formation, were......BACKGROUND: Postoperative pain relief may be improved by reducing sensitization of nociceptive pathways caused by surgical trauma. Such a reduction may depend on the timing and efficacy of analgesia and the duration of the nociceptive block versus the duration of the nociceptive input. We examined...... compared to the opposite unblocked leg for 12 h after bilateral thermal injuries (15 x 25 mm, 49 degrees C for 5 min) in 20 healthy volunteers. Recovery from the block was identified by return of sensation to cold. RESULTS: Six subjects were excluded because of insufficient initial block (2 subjects) or...

  6. Pharmacogenomic study of the role of the nociceptin/orphanin FQ receptor and opioid receptors in diabetic hyperalgesia.

    Science.gov (United States)

    Rutten, Kris; Tzschentke, Thomas M; Koch, Thomas; Schiene, Klaus; Christoph, Thomas

    2014-10-15

    Targeting functionally independent receptors may provide synergistic analgesic effects in neuropathic pain. To examine the interdependency between different opioid receptors (µ-opioid peptide [MOP], δ-opioid peptide [DOP] and κ-opioid peptide [KOP]) and the nociceptin/orphanin FQ peptide (NOP) receptor in streptozotocin (STZ)-induced diabetic polyneuropathy, nocifensive activity was measured using a hot plate test in wild-type and NOP, MOP, DOP and KOP receptor knockout mice in response to the selective receptor agonists Ro65-6570, morphine, SNC-80 and U50488H, or vehicle. Nocifensive activity was similar in non-diabetic wild-type and knockout mice at baseline, before agonist or vehicle administration. STZ-induced diabetes significantly increased heat sensitivity in all mouse strains, but MOP, DOP and KOP receptor knockouts showed a smaller degree of hyperalgesia than wild-type mice and NOP receptor knockouts. For each agonist, a significant antihyperalgesic effect was observed in wild-type diabetic mice (all Pfunctional independence, may yield an effective and favorable therapeutic analgesic profile. PMID:25169429

  7. A-Kinase Anchoring Protein Mediates TRPV1 Thermal Hyperalgesia through PKA Phosphorylation of TRPV1

    OpenAIRE

    Jeske, Nathaniel A.; Diogenes, Anibal; Ruparel, Nikita B.; Fehrenbacher, Jill C.; Henry, Michael; Akopian, Armen N.; Hargreaves, Kenneth M.

    2008-01-01

    Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-Kinase Anchoring Protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) ne...

  8. Resiniferatoxin (RTX) Causes a Uniquely Protracted Musculoskeletal Hyperalgesia in Mice by Activation of TRPV1 Receptors

    OpenAIRE

    Abdelhamid, Ramy E.; Kovács, Katalin J.; Honda, Christopher N.; Nunez, Myra G.; Larson, Alice A.

    2013-01-01

    Inactivation of TRPV1 receptors is one approach to analgesic drug development. However, TRPV1 receptors exert different effects on each modality of pain. Because muscle pain is clinically important, we compared the effect of TRPV1 ligands on musculoskeletal nociception to that on thermal and tactile nociception. Injected parenterally, capsaicin had no effect on von Frey fiber responses (tactile) but induced a transient hypothermia and hyperalgesia in both the tail flick (thermal) and grip for...

  9. Intrathecal cannabinoid-1 receptor agonist prevents referred hyperalgesia in acute acrolein-induced cystitis in rats

    OpenAIRE

    Jones, Marsha Ritter; Wang, Zun-Yi; Bjorling, Dale E

    2015-01-01

    We investigated the capacity of intrathecal arachidonyl-2’-chloroethylamide (ACEA), a cannabinoid-1 receptor (CB1R) agonist, to inhibit referred hyperalgesia and increased bladder contractility resulting from acute acrolein-induced cystitis in rats. 24 female rats were divided into 4 groups: 1) intrathecal vehicle/intravesical saline; 2) intrathecal vehicle/intravesical acrolein; 3) intrathecal ACEA/intravesical saline; and 4) intrathecal ACEA/intravesical acrolein. Bladder catheters were pla...

  10. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

    OpenAIRE

    Wienemann, Tobias; Chantelau, Ernst A; Koller, Armin

    2014-01-01

    Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy).Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral fo...

  11. Exacerbated Mechanical Hyperalgesia in Rats with Genetically Predisposed Depressive Behavior: Role of Melatonin and NMDA Receptors

    OpenAIRE

    Wang, Shuxing; Tian, Yinghong; Song, Li; Lim, Grewo; Tan, Yonghui; You, Zerong; Chen, Lucy; Mao, Jianren

    2012-01-01

    A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. In this study, we showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior ...

  12. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger;

    2011-01-01

    the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used in...... experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare)....

  13. Toxoplasma gondii Infection Promotes Neuroinflammation Through Cytokine Networks and Induced Hyperalgesia in BALB/c Mice.

    Science.gov (United States)

    Mahmoudvand, Hossein; Ziaali, Naser; Ghazvini, Hamed; Shojaee, Saeideh; Keshavarz, Hossein; Esmaeilpour, Khadijeh; Sheibani, Vahid

    2016-02-01

    We hypothesized that in Toxoplasma gondii infection, communication among immune cells promotes neuroinflammation through cytokine networks and induces pain sensitivity under conditions of neuropathic pain. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii to BALB/c mice. Amitriptyline (20 mg/kg, i.p., 1/day) administrated to animals for 7 days before behavioral tests. Pain behavioral tests including tail flick, hot plate, and formalin test were evaluated in all the groups. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were examined by real-time PCR. Results revealed that T. gondii induce hyperalgesia in the infected mice, whereas amitriptyline showed a promising effect against the hyperalgesia induced by Toxoplasma infection. The mRNA levels of the aforementioned cytokines significantly (P < 0.05) increased in the infected mice compared to the uninfected ones. Obtained findings suggested that T. gondii infection could promote neuroinflammation through cytokine networks and induced hyperalgesia in BALB/c mice, whereas amitriptyline as an analgesic drug reverses them. PMID:26490968

  14. Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay.

    Science.gov (United States)

    Kumada, A; Matsuka, Y; Spigelman, I; Maruhama, K; Yamamoto, Y; Neubert, J K; Nolan, T A; Watanabe, K; Maekawa, K; Kamioka, H; Yamashiro, T; Kuboki, T; Oguma, K

    2012-01-01

    Recent studies have shown that infraorbital nerve constriction (IoNC)-induced mechanical allodynia has been attenuated by administration of highly purified 150-kDa Botulinum neurotoxin type A (BoNT/A). Here, we extend these studies to determine whether BoNT/A could attenuate IoNC-induced symptoms of thermal hyperalgesia. Instead of testing head withdrawal thresholds, a thermal operant assay was used to evaluate cortical processing of sensory input following IoNC. In this assay, a fasted rat's desire to obtain a food reward (sweetened condensed milk) is coupled to its ability to tolerate facial contact with a warm (45 °C) thermode. Bilateral IoNC decreased the ratio of thermode contact duration/event, which is an indicative of thermal hyperalgesia. BoNT/A injection intradermally in the area of infraorbital nerve (IoN) innervation 7 days after IoNC resulted in decreased number of facial contacts and increased the ratio of contact duration/event (measured at 14 days after IoNC). The BoNT/A (2-200 pg) effects were dose dependent and statistically significant at 100 and 200 pg (P < 0·05). Complete reversal of thermal hyperalgesia symptoms was obtained with a 200-pg dose, without affecting sham rat behaviour. Off-site (neck) injection of BoNT/A did not relieve thermal hyperalgesia, while co-injection of BoNT/A with a neutralising antibody in the area of IoN innervation prevented relief of thermal hyperalgesia. Neither IoNC nor BoNT/A injection affected operant assay parameters with a 24 °C thermode, indicating selectivity of thermal hyperalgesia measurements. These results strongly suggest that intradermal injection of BoNT/A in the area of IoN innervation alleviates IoNC-induced thermal hyperalgesia in an operant assay. PMID:21793870

  15. 血栓通对顺铂肾损伤大鼠的肾功能和氧化指标的影响%Effect of Xueshuantong on Renal Function and Oxidation Indexes in Cisplatin-induced Nephroxicity Rats

    Institute of Scientific and Technical Information of China (English)

    席加喜; 刘晓霞; 杨玉芳; 张春花; 刘华钢

    2012-01-01

    目的:研究血栓通对顺铂肾损伤大鼠肾功能的保护作用和其对损伤大鼠氧化指标的影响.方法:采用顺铂(0.5 mg·kg-1)尾静脉注射的方法制造顺铂肾毒性模型.将72只大鼠随机分为6组,空白组、模型组、安磷汀阳性药物组、血栓通低剂、中、高剂量组(15.63,31.35,62.70 mg·kg-1).分别给药处理10d后,观察大鼠24 h尿蛋白量、尿N-乙酰β-D氨基葡萄糖苷酶NAG,血清中肌酐、尿素氮,肾组织匀浆中超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MAD)含量及肾组织的病理变化.结果:与模型组比较,各治疗组大鼠血肌酐、血清尿素氮,24h尿蛋白量、尿NAG的含量明显降低,肾组织匀浆中SOD活性、GSH-Px活性明显增高,MAD含量明显降低(P <0.01,P<0.05);肾脏的病理变化明显减轻.结论:血栓通能有效改善顺铂肾损伤大鼠肾功能,降低肾组织氧化水平,减轻肾脏的病理变化,对大鼠顺铂肾损伤有保护作用.%Objective: To study the protective effect of Xueshuantong against cisplatin-induced nephrotoxicity. Method; Female SD rats were randomly divided into six groups; normal saline (NS) group, model group, positive control group and the high dose group, middle dose group and low dose group of Xueshuantong, with 12 rats in each group. The model rats with nephrotoxicity were duplicated with injection of cisplatin by vena caudalis. Rats in model group, positive control group and the high dose group, middle dose group and low dose group of Xueshuantong were treated by amifostine, 0. 1 mg · kg-1, Xueshuantong, 15. 63 , 31. 35, 62.70 mg-kg-1 once a day. The changes of serum creatinine (SCr), blood urea nitrogen (BUN), W-acetyl-beta-D glucosa minidase (NAG), urine protein/24 h, the content of malondialdehyde ( MD A) and the activity of superoxide dismutase (SOD) , glutathione peroxidase (GSH-Px) were measured and renal structure was observed after 10 days of

  16. Optokinetic stimulation increases limb pain and forehead hyperalgesia in complex regional pain syndrome

    DEFF Research Database (Denmark)

    Knudsen, Lone F.; Drummond, Peter D.

    2015-01-01

    investigate the mechanisms underlying the link between sensory conflicts and pain in CRPS using optokinetic stimulation (OKS) - a method known to induce motion sickness. METHODS: Twenty-one CRPS patients underwent OKS and rated symptoms of motion sickness. Patients also rated limb pain and pain...... subgroup of nauseated patients who withdrew early from OKS, hyperalgesia to pressure in the ipsilateral forehead persisted longer than in the remaining participants. Sharpness sensations remained constant at all sites. CONCLUSIONS: Sensory conflicts may facilitate pain in CRPS by activating the mechanisms...

  17. Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans

    DEFF Research Database (Denmark)

    Andersen, H.; Arendt-Nielsen, L.; Svensson, P.; Danneskiold-Samsoe, B.; Graven-Nielsen, T.

    2008-01-01

    longus and at the web between 1st and 2nd metatarsal (central involvement). One day after the NGF/control injections, hypertonic saline (0.5 ml, 5.8%) was injected into the left and right TA to study the pain response to chemical stimulation of the hyperalgesic muscle tissue. Scores on a modified Likert......Intramuscular injection of nerve growth factor (NGF) has been shown to induce long-term sensitisation and time-dependent hyperalgesia indicating potential involvement of both central and peripheral pain mechanisms. This double-blind placebo-controlled study was designed to describe the spatial...

  18. Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

    DEFF Research Database (Denmark)

    O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas;

    2007-01-01

    demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus and...... in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the...

  19. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars;

    2000-01-01

    We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments....... Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following...... were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the...

  20. A PROSPECTIVE OBSERVATIONAL STUDY TO COMPARE THE ANTIEMETIC EFFICACY AND SAFETY PROFILE OF TWO COMBINATIONS NAMELY ONDANSETRON-DEXAMETHASONE VERSUS PALONOSETRON-DEXAMETHASONE IN PROPHYLAXIS OF CISPLATIN INDUCED EMESIS

    Directory of Open Access Journals (Sweden)

    Sneha Prabh

    2016-04-01

    Full Text Available BACKGROUND Chemotherapy Induced Nausea and Vomiting (CINV are among the most distressing symptoms for cancer patients and preventing this can lead to a better treatment outcome. Serotonin (5-HT3 receptor antagonists in combination with Dexamethasone remains the mainstay of treatment in chemotherapy-induced emesis. The purpose of this study is to compare the antiemetic efficacy and safety profile of Ondansetron, a first generation 5-HT3 receptor antagonist versus Palonosetron, a second generation 5-HT3 receptor antagonist, both in combination with Dexamethasone, in Cisplatin-induced emesis. This prospective observational study done over a period of 1 year included 120 adult patients scheduled for their first cycle of Cisplatin based chemotherapy regimen in a tertiary care centre of Kerala. These patients were divided into two groups of 60 patients each; group 1 received Ondansetron (8 mg with Dexamethasone (8 mg and group 2 received Palonosetron (0.25 mg with Dexamethasone (8 mg combinations both intravenously 30 minutes prior to Cisplatin administration. Efficacy of two regimens were compared in terms of complete response rate [CR rate: no emesis and no significant nausea (nausea ˂3 in nausea scale] between two groups, in acute (0-24 hours and delayed (˃24-120 hours phases of 1st and 2nd cycles of Cisplatin chemotherapy. Other parameters that were assessed include number of emetic episodes, frequency of nausea and treatment related adverse effects in both the groups. Nausea and vomiting was assessed using Multinational association of supportive care in cancer Antiemetic Tool (MAT. Results were analysed using Chi-square test. Analysis showed that Palonosetron-Dexamethasone combination was found to be more effective in preventing CINV in terms of CR rate and significantly higher responses were seen in delayed phases of both 1st (73.3% vs 50%, P value=0.009 and 2nd (78.3% vs 55%, P value=0.007 cycles of Cisplatin chemotherapy. When individual

  1. Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Woolf Clifford J

    2005-12-01

    Full Text Available Abstract Background Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia. To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.

  2. Role of spinal glial cells in bee-toxin-induced spontaneous pain, hyperalgesia, and inflammation

    Directory of Open Access Journals (Sweden)

    Yao LU

    2012-08-01

    Full Text Available Objective To observe the effects of intrathecal injection of fluorocitrate, a glial metabolism inhibitor, on bee-toxin-induced spontaneous pain, hyperalgesia and inflammatory response. Methods Forty adult male SD rats with intrathecal catheterization were randomly divided into five groups (8 each: (1 bee-toxin alone group; (2 vehicle (solvent group; (3 low dose (1nmol fluorocitrate group; (4 middle dose (10nmol fluorocitrate group; (5 high dose (50nmol fluorocitrate group. After the measurement of rat paw withdrawal mechanical threshold (PWMT and paw volume (PV, the drug or vehicle was administered intrathecally. Twenty minutes later, bee-toxin (0.2mg/50μl was intraplantarly injected into the left hind paw of every rat, and spontaneous flinching reflexes (SFR were observed instantly for 1 hour. Two hours later, PWMT and PV were measured again. Results Intraplantar injection of bee-toxin into one hind paw of rat induced persistent SFR lasting for 1 hour, with PWMT decreased and PV increased in the injected paw. Compared with control group, pretreatment with intrathecal injection of fluorocitrate produced a significant inhibition of bee-toxin-induced persistent SFR (P < 0.05, P < 0.01, decreased the PWMT in a dose-dependent manner (P < 0.05, but it had no effect on bee-toxin-induced paw edema. Conclusion Activation of spinal glial cells may participate in bee-toxin-induced spontaneous pain and mechanical hyperalgesia, but not inflammatory response.

  3. Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

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    Theresa Alexandra Mattioli

    Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

  4. Self-reported recovery is associated with improvement in localized hyperalgesia among adolescent females with patellofemoral pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Roos, Ewa Maria; Olesen, Jens Lykkegaard; Rasmussen, Sten; Arendt-Nielsen, Lars

    2016-01-01

    female adolescents. Changes in localised and distal hyperalgesia from baseline to follow-up were compared to self-reported recovery. Adolescents were categorized as recovered if they rated themselves as "completely recovered" or "strongly recovered" (category 1 or 2) on a 7-point Likert scale. RESULTS...

  5. A possible correlation between oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats.

    Science.gov (United States)

    Chow, Lok-Hi; Tao, Pao-Luh; Chen, Jin-Chung; Liao, Ruey-Ming; Chang, En-Pei; Huang, Eagle Yi-Kung

    2013-01-01

    In our previous study, we showed that intrathecal (i.t.) administration of angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor, attenuated inflammatory hyperalgesia in rats. Using the plantar test in rats with carrageenan-induced paw inflammation, we investigated the possible mechanism(s) of this effect. Because i.t. oxytocin was reported to produce a dose-dependent anti-hyperalgesia in rats with inflammation, we speculate that there is a possible correlation between oxytocin-induced and Ang IV-induced anti-hyperalgesia. Using i.t. co-administered atosiban (oxytocin receptor antagonist), the anti-hyperalgesia by Ang IV was completely abolished. This indicated that oxytocin could be the major IRAP substrate responsible for the anti-hyperalgesia by Ang IV. When Ang IV was co-administered with a low dose of oxytocin, there was a significant enhancing effect of Ang IV on oxytocin-induced anti-hyperalgesia. In recent reports, electrical stimulation on the paraventricular hypothalamic nucleus (PVN) was proved to increase oxytocin release at the spinal cord. Our results also showed that Ang IV could prolong the anti-hyperalgesia induced by PVN stimulation. This suggests a possible protective effect of Ang IV on endogenous oxytocin degradation/dysfunctioning. Moreover, we examined the local effect of intraplantarly injected Ang IV in the same model. Our results showed no effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may not regulate the peripheral inflammatory process. Overall, our study suggests that Ang IV may act through the inhibition of the activity of IRAP to reduce the degradation of oxytocin at the spinal cord, thereby leading to anti-hyperalgesia in rats with inflammation. PMID:23142109

  6. BK channels in microglia are required for morphine-induced hyperalgesia.

    Science.gov (United States)

    Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L; Nakata, Takahiro; Wu, Zhou; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi

    2016-01-01

    Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca(2+)-activated K(+) (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance. PMID:27241733

  7. Pharmacological inhibition of eicosanoid synthesis and hyperalgesia in yeast-injected rat paws

    International Nuclear Information System (INIS)

    Brewer's yeast caused an inflammation characterized by edema and hyperalgesia when injected into the hindpaw of a rat. These events were temporally distinct and each was associated with increases of specific arachidonic and oxygenation products. As determined by radioimmunoassay (RIA) on whole paw lipid extracts, the 5-lipoxygenase (5-LO) products, leukotrienes C4 and D4 and 5-hydroxyeicosatetraendic acid (5-HETE) were synthesized concurrently with the onset of edema (maximal at 15 minutes after yeast injection). The hyperalgesic phase of the inflammation (3-4 hr after yeast injection) was associated with increased tissue levels of the cyclooxygenase (CO) products, prostaglandin E2 and thromboxane B2 (TXB2) as well as increases in levels of the 5-LO products, leukotriene B4 (LTB4) and 5-HETE. Pharmacological agents modulated the synthesis of eicosanoids and suppressed the hyperalgesic response

  8. Is mechanism and symptom-based analgesia an answer to opioid-Induced hyperalgesia?

    Directory of Open Access Journals (Sweden)

    Mayank Gupta

    2015-01-01

    Full Text Available "Cancer Pain" and "Pain in cancer patient" are not synonymous. Opioid-induced Hyperalgesia (OIH is a paradoxical state of nociceptive sensitization caused by exposure to opioids. Neuropathic pain is only partially responsive to opioids; injudicious increase in dose of opioids in neuropathic pain may not only result in inadequate pain relief but also OIH. Majority of literature on OIH is in non-cancer pain with systemic use of opioids. We describe the development and successful treatment of OIH in a 55-year-old male patient with Small cell Carcinoma Lung. Opioid tapering, rotation, systemic desensitization helps in combatting OIH. The use of anti-neuropathic adjuvant analgesics helps not only in preventing and treating OIH but also in understanding putative mechanisms underlying neuropathic pain and OIH.

  9. Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing

    DEFF Research Database (Denmark)

    Larsen, Peter; Elsøe, Rasmus; Graven-Nielsen, Thomas;

    2016-01-01

    OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months...... postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed...... bilaterally by pain pressure thresholds (PPTs). RESULTS: The mean age at the time of fracture was 42.9 years. Twelve months after surgery, the pain intensity for worst pain during the last 24 hours was 1.8 ± 2.7 cm. The PPTs progressively increased from 6 weeks after surgery to 12 months postoperatively for...

  10. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

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    Tobias Wienemann

    2014-11-01

    Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

  11. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

    Science.gov (United States)

    Wienemann, Tobias; Chantelau, Ernst A.; Koller, Armin

    2014-01-01

    Introduction and objective Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). Design and methods A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®). Results In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Conclusion Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking. PMID:25397867

  12. Nocebo hyperalgesia: contributions of social observation and body-related cognitive styles

    Science.gov (United States)

    Vögtle, Elisabeth; Kröner-Herwig, Birgit; Barke, Antonia

    2016-01-01

    Purpose Recently, it has been shown that nocebo hyperalgesia can be acquired through observational learning. The aim of this study was to investigate socially induced nocebo hyperalgesia and its relationship with pain catastrophizing, somatic complaints, hypochondriacal concerns, and empathy. Participants and methods Ninety-seven women (43.1±15.5 years) were randomly assigned to one of the two conditions. Participants in the nocebo condition (NC) watched a video in which a female model displayed more pain when an ointment was applied and less pain when no ointment was applied. In the control condition (CC), the model demonstrated low pain with and without the ointment. Subsequently, all participants received three pressure pain stimuli (60 seconds) on each hand. On one hand, the ointment was applied prior to the stimulation. The order of the stimulation of the fingers (middle, index, or ring finger), the side of ointment application (left or right hand), and the side with which the stimulation began were randomized within each group and balanced across the groups. Depending on the randomization, the pressure pain application started with or without ointment and on the left or right hand. Pain ratings on a numerical rating scale (0–10) were collected. In addition, the participants completed questionnaires regarding body-related cognitive styles and empathy. Results There was a significant difference in the pain ratings between the CC and the NC. The effect of ointment application was also significant, but no interaction between condition and ointment application was found. Only in the CC did the nocebo response correlate with hypochondriacal concerns and somatic complaints. Conclusion Application of an ointment as well as the observation of a model demonstrating more pain after a treatment produced elevated pain ratings. Cognitive styles were not related to the socially induced nocebo response, but were related to the nocebo response in the CC.

  13. Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia

    OpenAIRE

    Chen, Yumei; Zhu, Bo; Zhang, Hongping; Ding, Ding; Liu, Xishi; Guo, Sun-Wei

    2014-01-01

    We have previously reported that induction of adenomyosis in mice results in progressive hyperalgesia, uterine hyperactivity, and elevated plasma corticosterone levels and that epigallocatechin-3-gallate (EGCG) treatment dose dependently suppressed myometrial infiltration and improved generalized hyperalgesia. In this study, we examined whether adenomyosis induced in mice results in the loss of GABAergic inhibition as manifested by the diminished glutamate decarboxylase (GAD) 65-expressing ne...

  14. Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin (Corilagin) Rich Extracts of Phyllanthus amarus in Carrageenan-induced Thermal and Mechanical Chronic Muscle Hyperalgesia.

    Science.gov (United States)

    Chopade, Atul R; Sayyad, F J

    2015-08-01

    The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. PMID:25974715

  15. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization

    OpenAIRE

    Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

    2016-01-01

    Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1wee...

  16. Effect of Electroacupuncture on Visceral Hyperalgesia, Serotonin and Fos Expression in an Animal Model of Irritable Bowel Syndrome

    OpenAIRE

    Wu, Justin CY; Ziea, Eric TC; Lao, Lixing; Lam, Emma FC; Chan, Catherine SM; Liang, Angela YQ; Chu, Sunny LH; Yew, David TW; Berman, Brian M; Sung, Joseph JY

    2010-01-01

    Background/Aims While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. Methods Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another gro...

  17. Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis

    OpenAIRE

    Fu, Weisi; Taylor, Bradley K.

    2015-01-01

    Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. 4 weeks after induction of experimental autoimmune encephalomyelitis, we found that intrathecal administration of JWH-133 (10–100 μg...

  18. Chronic pain in patients with the hypermobility type of Ehlers-Danlos syndrome: evidence for generalized hyperalgesia.

    Science.gov (United States)

    Rombaut, Lies; Scheper, Mark; De Wandele, Inge; De Vries, Janneke; Meeus, Mira; Malfait, Fransiska; Engelbert, Raoul; Calders, Patrick

    2015-06-01

    Chronic widespread pain is highly present in patients with the Ehlers-Danlos syndrome hypermobility type (EDS-HT), but up to now, evidence for generalized hyperalgesia is lacking. The aim of this study is to investigate whether pressure pain thresholds (PPTs) at both symptomatic and asymptomatic body areas differ in EDS-HT patients compared to healthy subjects. Twenty-three women with EDS-HT and 23 gender- and age-matched healthy controls participated. All subjects marked on Margolis Pain Diagram where they felt pain lasting longer than 24 h in the past 4 weeks. Then, they completed several questionnaires assessing pain cognitions, fatigue, disability, and general health status, in order to take the possible influence of these factors on PPTs into account. Patients also completed a form concerning the type of pain they experienced. Thereupon, a blinded researcher assessed PPTs at 14 body locations on the trunk and extremities. PPTs were compared for the two complete groups. In addition, PPTs of patients and controls who did not report pain in a respective zone were compared. PPTs of the patients were significantly lower compared to those of the control group, also when pain-free samples per zone were compared. The mean (SD) PPT was 2.9 (1.62) kg/cm(2) in the EDS-HT patients and 5.2 (1.88) kg/cm(2) in the controls (P pain component was likely present. This study provides evidence for the existence of hyperalgesia even in asymptomatic areas (generalized secondary hyperalgesia). The generalized hyperalgesia may represent the involvement of a sensitized central nervous system, which inquires an adapted pain management for this patient group. PMID:24487572

  19. Anti-Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro-Inflammatory Mediators.

    Science.gov (United States)

    Singh, Ajeet Kumar; Vinayak, Manjula

    2016-07-01

    Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti-hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c-Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL-1β, TNF-α and IL-6 as well as inflammatory enzymes COX-2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX-2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti-nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27060370

  20. Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.

    Science.gov (United States)

    Dolan, Sharron; Gunn, Mark Donald; Crossan, Claire; Nolan, Andrea Mary

    2011-09-01

    This study set out to characterize the contribution of group III metabotropic glutamate receptor 7 activation to nociceptive behaviour and mechanical hypersensitivity in a novel formalin test in sheep. The mGlu receptor 7 allosteric agonist, N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082; 2-20 mM), the nonselective group III mGlu receptor agonist L-(+)-2-amino-4-phosphonobutyric acid (0.2-20 mM) and drug vehicle were injected intrathecally into naive subjects (n=7 per group), or 5 min preformalin (3%; 0.2 ml)/saline injection (intradermal), into the lower forelimb of adult female sheep (n=5-7 per group). Forelimb withdrawal thresholds to noxious mechanical stimulation and pain behaviours (time spent nonweight bearing or flinching) were assessed for up to 180 min. Formalin induced a characteristic biphasic pain-behaviour response and mechanical hyperalgesia between 1-5 and 30-120 min postinjection. Treatment with AMN082, but not L-(+)-2-amino-4-phosphonobutyric acid significantly inhibited both early and late phase formalin-induced hyperalgesia and pain behaviours. AMN082 also induced a rapid but short lasting analgesia in naive subjects. These data suggest that enhancing endogenous metabotropic glutamate receptor 7 activity in spinal cord, using the novel allosteric modulator, AMN082, blocks pain and hyperalgesia, and may be of therapeutic benefit for the treatment of inflammatory pain. PMID:21597362

  1. Telemetric assessment of referred vaginal hyperalgesia and the effect of Indomethacin in a rat model of endometriosis

    Directory of Open Access Journals (Sweden)

    NataliaDmitrieva

    2012-08-01

    Full Text Available Symptoms of endometriosis, among others, include pelvic/abdominal and muscle pain. Non-steroidal anti-inflammatory agents are first-line treatment for this pain. Similar to women, rats with surgically-induced endometriosis (ENDO, but not its surgical control, exhibit vaginal hyperalgesia, which in rats is evidenced by a decreased threshold for the visceromotor response (VMR induced by vaginal distention. Here we assess the VMR in rats with implanted probes that telemetrically transmit EMG activity from the abdominal muscle. The feasibility and sensitivity of this technique for monitoring the VMR threshold across the estrous cycle and the influence of Indomethacin on ENDO-induced vaginal hyperalgesia were evaluated. VMR thresholds in response to vaginal distention with an infusion pump were measured in different estrous stages. Indomethacin (5 or 10 mg/kg i.p.or s.c. was injected in proestrous rats and 40-60 min later the VMR threshold was measured. The VMR threshold varied across the estrous cycle only in ENDO rats, being lowest in proestrus. Indomethacin increased this threshold in proestrous ENDO rats. These results show that telemetric assessment of the VMR is a sensitive tool, suitable for long-term studies in conscious rats. The results with this technique also suggest that ENDO-associated vaginal hyperalgesia involves COX activity, the feature that also underlies inflammatory pains.

  2. Nocebo hyperalgesia: contributions of social observation and body-related cognitive styles

    Directory of Open Access Journals (Sweden)

    Vögtle E

    2016-04-01

    Full Text Available Elisabeth Vögtle,1 Birgit Kröner-Herwig,1 Antonia Barke21Department of Clinical Psychology and Psychotherapy, Georg-Elias-Müller-Institute for Psychology, University of Göttingen, Göttingen, 2Department of Psychology, Division of Clinical Psychology and Psychotherapy, Philipps University Marburg, Marburg, Germany Purpose: Recently, it has been shown that nocebo hyperalgesia can be acquired through observational learning. The aim of this study was to investigate socially induced nocebo hyperalgesia and its relationship with pain catastrophizing, somatic complaints, hypochondriacal concerns, and empathy. Participants and methods: Ninety-seven women (43.1±15.5 years were randomly assigned to one of the two conditions. Participants in the nocebo condition (NC watched a video in which a female model displayed more pain when an ointment was applied and less pain when no ointment was applied. In the control condition (CC, the model demonstrated low pain with and without the ointment. Subsequently, all participants received three pressure pain stimuli (60 seconds on each hand. On one hand, the ointment was applied prior to the stimulation. The order of the stimulation of the fingers (middle, index, or ring finger, the side of ointment application (left or right hand, and the side with which the stimulation began were randomized within each group and balanced across the groups. Depending on the randomization, the pressure pain application started with or without ointment and on the left or right hand. Pain ratings on a numerical rating scale (0–10 were collected. In addition, the participants completed questionnaires regarding body-related cognitive styles and empathy. Results: There was a significant difference in the pain ratings between the CC and the NC. The effect of ointment application was also significant, but no interaction between condition and ointment application was found. Only in the CC did the nocebo response correlate with

  3. Ameliorative effect of Armillariella tabescens on cisplatin-induced gastrointestinal tract reaction in the rat%亮菌对顺铂化疗所诱发胃肠道反应的防治效果

    Institute of Scientific and Technical Information of China (English)

    杜静; 李平; 孙鑫; 张梅

    2011-01-01

    kaolin, food, water and body weight. Results 24-72 h after cisplatin administration, in the middle dose Armillariella tabescens group, the high dose Armillariella tabeseens group and the ondansetron group, the kaolin intake was significantly lower than that in the model group, respectively (P < 0.05). The most significant difference was between the high dose Armillariella tabeecens group [(0.58 ±0.23)g/24 h]and the control group [(2. 16 ±0.98) g/24 h] at 24 h after cisplatin administration. The variables, such as consumption of food during 48-72 h ( P < 0.05 ), water during 48-72 h ( P < 0. 05 ), and body weight at 72 h (P <0.05) in the middle dose Armillariella tabescens group were significantly higher than those in the model group, but no statistically significant difference between the ondansetron group and the model group (P > 0. 05 ). Conclusions Armillariella tabescens can effectively inhibit the cisplatin-induced pica response, and the middle dose Armillariella tabescens group is significantly better than the model group in improving the food intake reduction, water intake reduction and body weight loss.

  4. An investigation of the antinociceptive effects of Riluzole in hyperalgesia models of mice

    Institute of Scientific and Technical Information of China (English)

    Xiaoping Xia; Zhenliang Ma; Yinming Zeng

    2006-01-01

    Objective: To investigate the antinociceptive effects of Riluzole administered intraperitoneally in three hyperalgesia model of mice. Methods: Antinociceptive tests in C57BL mice were investigated with formalin test、acetic acid induced writhing test and tail-immersion test. The effects of intraperitoneally Riluzole 2 mg/kg、4 mg/kg and 8 mg/kg on the pain threshold were observed. Result: We found that i.p. treatment with Riluzole (4 mg/kg and 8 mg/kg) blocked the second phase flinching behavior compared with vehicle (P < 0.05), but not during the first phase in the formalin test. In addition to the formalin test, Riluzole at different dose (from 2 to 8 mg/kg) attenuated acetic acid induced writhing response when compared to vehicle group (P < 0.05). In the tail-immersion test, Riluzole at the highest dose (8 mg/kg) caused significant increase in tail flick response latency as compared to vehicle animals or compared with Baseline (P < 0.05). Conclusion: Our results suggest that glutamate release inhibitor Riluzole can attenuate nociceptive behavior and has differrent antinociceptive characteristic according to the various pain models.

  5. Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.

    Science.gov (United States)

    Johansson, B; Halldner, L; Dunwiddie, T V; Masino, S A; Poelchen, W; Giménez-Llort, L; Escorihuela, R M; Fernández-Teruel, A; Wiesenfeld-Hallin, Z; Xu, X J; Hårdemark, A; Betsholtz, C; Herlenius, E; Fredholm, B B

    2001-07-31

    Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A(1)R (A(1)R(-/-)). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R. In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A(1)Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important. PMID:11470917

  6. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats.

    Science.gov (United States)

    Liu, Yu-Ting; Shao, Yen-Wen; Yen, Chen-Tung; Shaw, Fu-Zen

    2014-05-28

    Fibromyalgia is a prevalent disorder characterized by chronic widespread pain (CWP) and complex comorbid symptoms. A CWP model is developed through repeated unilateral intramuscular injections of acid saline resulting in bilateral mechanical hyperalgesia in rats. The present study aims to evaluate whether both anxious and depressive comorbidities exist in this acid-induced pain model, similarly to patients with CWP syndromes. The anxiety-like behaviors were evaluated using the open field and elevated plus maze tests, and depression-like behaviors were measured by the forced swimming, sucrose consumption, and sucrose preference tests. The pain group receiving acidic saline displayed significantly lower paw withdrawal thresholds for 4weeks than animals in the vehicle group after repetitive intramuscular injections. The pain group showed a significantly shorter duration of exploring the central zone of the open field and the open arms of the elevated plus maze compared to the vehicle group. The pain group had a significantly lower preference for and consumption of the hedonic sucrose. Moreover, rats with chronic pain showed significantly longer immobility than the vehicle group in the forced swimming test. The results indicate that psychiatric behaviors are exacerbated in the CWP model. This study provides evidence for the validity of the acid-induced pain model analogous to patients with CWP syndromes. PMID:24726391

  7. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas;

    2000-01-01

    The present study examined distribution and duration of muscle hyperalgesia to pressure stimuli after intramuscular bolus-infusions of serotonin (5-HT, 20 nmol) and bradykinin (BKN, 10 nmol) in 10 volunteers. Infusions were given into the tibialis anterior (TA) muscle over 20 s with an inter-infusions...... interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer......, 40, and 60 min after infusions. The VAS-peak after BKN was significantly higher (P<0.05) compared with 5-HT and the second infusion of NaCl. The duration of the increase in VAS after 5-HT+BKN was significantly longer (P<0.05) compared with the infusions of NaCl. The local pain area after infusion of...

  8. Auraptenol attenuates vincristine-induced mechanical hyperalgesia through serotonin 5-HT1A receptors.

    Science.gov (United States)

    Wang, Yunfei; Cao, Shu-e; Tian, Jianmin; Liu, Guozhe; Zhang, Xiaoran; Li, Pingfa

    2013-01-01

    Common chemotherapeutic agents such as vincristine often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is refractory to common analgesics and represents a challenging clinical issue. Angelicae dahuricae radix is an old traditional Chinese medicine with demonstrated analgesic efficacy in humans. However, the active component(s) that attribute to the analgesic action have not been identified. This work described the anti-hyperalgesic effect of one coumarin component, auraptenol, in a mouse model of chemotherapeutic agent vincristine-induced neuropathic pain. We reported that auraptenol dose-dependently reverted the mechanical hyperalgesia in mice within the dose range of 0.05-0.8 mg/kg. In addition, the anti-hyperalgesic effect of auraptenol was significantly blocked by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). Within the dose range studied, auraptenol did not significantly alter the general locomotor activity in mice. Taken together, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust analgesic efficacy in mice. These data support further studies to assess the potential of auraptenol as a novel analgesic for the management of neuropathic pain. PMID:24287473

  9. Atenolol Reduces Leishmania major-Induced Hyperalgesia and TNF-α Without Affecting IL-1β or Keratinocyte Derived Chemokines (KC)

    Science.gov (United States)

    Karam, Marc C.; Merckbawi, Rana; Salman, Sara; Mobasheri, Ali

    2016-01-01

    Infection with a high dose of the intracellular parasitic protozoan Leishmania major induces a sustained hyperalgesia in susceptible BALB/c mice accompanied by up-regulation of the pro-inflammatory cytokines IL-1β and IL-6. Interleukin-13 (IL-13) has been shown to reduce this hyperalgesia (despite increased levels of IL-6) and the levels of IL-1β during and after the treatment period. These findings favor the cytokine cascade leading to the production of sympathetic amines (involving TNF-α and KC) over prostaglandins (involving IL-lβ and IL-6) as the final mediators of hyperalgesia. The aim of this study was to investigate the effect of daily treatment with the β-blockers atenolol on L. major-induced inflammation in mice with respect to hyperalgesia as well as the levels of TNF-α and KC (the analog of IL-8 in mice). Our data demonstrates that atenolol is able to reduce the L. major induced sustained peripheral hyperalgesia, which does not seem to involve a direct role for neither IL-lβ nor KC. Moreover, our results show that TNF-α may play a pivotal and direct role in sensitizing the peripheral nerve endings (nociceptors) since its level was reduced during the period of atenolol treatment, which correlates well with the reduction of the observed peripheral, but not central, hyperalgesia. These findings contribute to a better understanding of the cytokine cascade leading to hyperalgesia and may lead to the development of new and more efficient medications for many types of pain. PMID:26913003

  10. Atenolol Reduces Leishmania major-Induced Hyperalgesia and TNF-α Without Affecting IL-1β or Keratinocyte Derived Chemokines (KC).

    Science.gov (United States)

    Karam, Marc C; Merckbawi, Rana; Salman, Sara; Mobasheri, Ali

    2016-01-01

    Infection with a high dose of the intracellular parasitic protozoan Leishmania major induces a sustained hyperalgesia in susceptible BALB/c mice accompanied by up-regulation of the pro-inflammatory cytokines IL-1β and IL-6. Interleukin-13 (IL-13) has been shown to reduce this hyperalgesia (despite increased levels of IL-6) and the levels of IL-1β during and after the treatment period. These findings favor the cytokine cascade leading to the production of sympathetic amines (involving TNF-α and KC) over prostaglandins (involving IL-lβ and IL-6) as the final mediators of hyperalgesia. The aim of this study was to investigate the effect of daily treatment with the β-blockers atenolol on L. major-induced inflammation in mice with respect to hyperalgesia as well as the levels of TNF-α and KC (the analog of IL-8 in mice). Our data demonstrates that atenolol is able to reduce the L. major induced sustained peripheral hyperalgesia, which does not seem to involve a direct role for neither IL-lβ nor KC. Moreover, our results show that TNF-α may play a pivotal and direct role in sensitizing the peripheral nerve endings (nociceptors) since its level was reduced during the period of atenolol treatment, which correlates well with the reduction of the observed peripheral, but not central, hyperalgesia. These findings contribute to a better understanding of the cytokine cascade leading to hyperalgesia and may lead to the development of new and more efficient medications for many types of pain. PMID:26913003

  11. The relationship of bone-tumor-induced spinal cord astrocyte activation and aromatase expression to mechanical hyperalgesia and cold hypersensitivity in intact female and ovariectomized mice.

    Science.gov (United States)

    Smeester, B A; O'Brien, E E; Michlitsch, K S; Lee, J-H; Beitz, A J

    2016-06-01

    Recently, our group established a relationship between tumor-induced spinal cord astrocyte activation and aromatase expression and the development of bone tumor nociception in male mice. As an extension of this work, we now report on the association of tumor-induced mechanical hyperalgesia and cold hypersensitivity to changes in spinal cord dorsal horn GFAP and aromatase expression in intact (INT) female mice and the effect of ovariectomy on these parameters. Implantation of fibrosarcoma cells produced robust mechanical hyperalgesia in INT animals, while ovariectomized (OVX) females had significantly less mechanical hyperalgesia. Cold hypersensitivity was apparent by post-implantation day 7 in INT and OVX females compared to their saline-injected controls and increased throughout the experiment. The decrease in mechanical hyperalgesia in OVX females was mirrored by significant decreases in spinal astrocyte activity in laminae I-II, III-IV, V-VI and X and aromatase expression in laminae V-VI and X in the dorsal horn of tumor-bearing animals. Administration of the aromatase inhibitor letrozole reduced tumor-induced hyperalgesia in INT females only suggesting that the tumor-induced increase in aromatase expression and its associated increase in spinal estrogen play a role in the development of bone tumor-induced hyperalgesia. Finally, intrathecal (i.t.) administration of 17β-estradiol caused a significant increase in tumor-induced hyperalgesia in INT tumor-bearing females. Since i.t. 17β-estradiol increases tumor pain and ovariectomy significantly decreases tumor pain, as well as spinal aromatase, estrogen may play a critical role in the spinal cord response to the changing tumor environment and the development of tumor-induced nociception. PMID:26995084

  12. Effects of systemic non-steroidal anti-inflammatory drugs on nociception during tail ischaemia and on reperfusion hyperalgesia in rats.

    Science.gov (United States)

    Gelgor, L.; Butkow, N.; Mitchell, D.

    1992-01-01

    1. We have investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) on nociception during ischaemia and on reperfusion hyperalgesia in rats. 2. We induced tail ischaemia in conscious rats by applying a tourniquet at the base of the tail until the rats exhibited co-ordinated escape behaviour when we released the tourniquet. 3. We assessed hyperalgesia by measuring the tail flick latency following tail immersion in water at 49 degrees C, before applying and immediately after releasing the tourniquet, and then at 30 min intervals for 2 h. 4. Intraperitoneal injection of NSAIDs prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia, nor on tail flick latency in the absence of prior ischaemia. However all the drugs attenuated reperfusion hyperalgesia in a log dose-dependent manner. Doses required to abolish hyperalgesia, were indomethacin 5 mg kg-1, diclofenac sodium 42 mg kg-1, ibuprofen 54 mg kg-1, dipyrone 168 mg kg-1 and paracetamol 170 mg kg-1. 5. We conclude that the mechanisms underlying nociception during ischaemia are not the same as those underlying reperfusion hyperalgesia. Moreover our procedure provides a rapid and more humane method for measuring the antinociceptive potency of NSAIDs. PMID:1559131

  13. Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

    Directory of Open Access Journals (Sweden)

    Marco Sisignano

    Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

  14. L-Tetrahydropalmatine alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice.

    Science.gov (United States)

    Zhou, Hai-Hui; Wu, Dan-Lian; Gao, Li-Yan; Fang, Yun; Ge, Wei-Hong

    2016-05-01

    Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund's adjuvant. To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund's adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg). Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor-mediated dopaminergic transmission. PMID:26981712

  15. Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats

    Directory of Open Access Journals (Sweden)

    Hofmann Cane

    2011-07-01

    Full Text Available Abstract Painful stimuli during neonatal stage may affect brain development and contribute to abnormal behaviors in adulthood. Very few specific therapies are available for this developmental disorder. A better understanding of the mechanisms and consequences of painful stimuli during the neonatal period is essential for the development of effective therapies. In this study, we examined brain reactions in a neonatal rat model of peripheral inflammatory pain. We focused on the inflammatory insult-induced brain responses and delayed changes in behavior and pain sensation. Postnatal day 3 pups received formalin injections into the paws once a day for 3 days. The insult induced dysregulation of several inflammatory factors in the brain and caused selective neuronal cell death in the cortex, hippocampus and hypothalamus. On postnatal day 21, rats that received the inflammatory nociceptive insult exhibited increased local cerebral blood flow in the somatosensory cortex, hyperalgesia, and decreased exploratory behaviors. Based on these observations, we tested recombinant human erythropoietin (rhEPO as a potential treatment to prevent the inflammatory pain-induced changes. rhEPO treatment (5,000 U/kg/day, i.p., coupled to formalin injections, ameliorated neuronal cell death and normalized the inflammatory response. Rats that received formalin plus rhEPO exhibited normal levels of cerebral blood flow, pain sensitivity and exploratory behavior. Treatment with rhEPO also restored normal brain and body weights that were reduced in the formalin group. These data suggest that severe inflammatory pain has adverse effects on brain development and rhEPO may be a possible therapy for the prevention and treatment of this developmental disorder.

  16. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

    Directory of Open Access Journals (Sweden)

    Nicholas S Gregory

    Full Text Available Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X and acid sensing ion channels (ASICs on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive or more than the sum of individual effects (synergistic is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm, lactate (10mM, and acidic pH (pH 6.0 produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol, on the other hand, showed no enhanced effects when combined with lactate (10mM or acidic pH (pH 6.0, i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

  17. Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice

    Directory of Open Access Journals (Sweden)

    Bian Xiling

    2011-10-01

    Full Text Available Abstract Background Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia. Results Using a forebrain specific αCaMKII promoter, we established a line of transgenic (Tg mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p. injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine. Conclusions Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.

  18. GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.

    Science.gov (United States)

    Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A; Lydic, Ralph

    2014-07-01

    The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (-18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss. PMID:24674578

  19. Warming Moxibustion Relieves Chronic Visceral Hyperalgesia in Rats: Relations to Spinal Dynorphin and Orphanin-FQ System

    OpenAIRE

    Li Qi; Hui-Rong Liu; Tao Yi; Lu-Yi Wu; Xi-Ru Liu; Chen Zhao; Yin Shi; Xiao-Peng Ma; Huan-Gan Wu

    2013-01-01

    As a twin therapy of acupuncture in traditional Chinese medicine, moxibustion has shown its effects in relieving abdominal pain in irritable bowel syndrome (IBS) patients and IBS rat models, but its mechanisms are largely unknown. In this paper, we determined the role of spinal dynorphin and orphanin-FQ system in analgesic effect of warming moxibustion (WM) on chronic visceral hyperalgesia (CVH) in IBS-like rat model. Here, we show that (1) repeated WM at bilateral ST25 and ST37 acupoints mar...

  20. Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα.

    Science.gov (United States)

    Zhang, Yanan; Song, Chengwei; Li, Haiou; Hou, Jingdong; Li, Dongliang

    2016-06-01

    Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a

  1. Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents

    OpenAIRE

    Patwardhan, Amol M.; Akopian, Armen N.; Ruparel, Nikita B.; Diogenes, Anibal; Weintraub, Susan T; Uhlson, Charis; Murphy, Robert C.; Hargreaves, Kenneth M.

    2010-01-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is the principal detector of noxious heat in the peripheral nervous system. TRPV1 is expressed in many nociceptors and is involved in heat-induced hyperalgesia and thermoregulation. The precise mechanism or mechanisms mediating the thermal sensitivity of TRPV1 are unknown. Here, we have shown that the oxidized linoleic acid metabolites 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE) are formed in mouse and rat skin biopsies b...

  2. Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats.

    Science.gov (United States)

    Li, Zhen; Li, Chenhong; Yin, Pingping; Wang, Zaijie Jim; Luo, Fang

    2016-10-01

    Opioid-induced hyperalgesia (OIH) is a less-studied phenomenon that has been reported in both preclinical and clinical studies. Although the underlying cause is not entirely understood, OIH is a real-life problem that affects millions of patients on a daily basis. Research has implicated the important contribution of Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) to OIH at the level of spinal nociceptors. To expand our understanding of the entire brain circuitry driving OIH, in this study we investigated the role of CaMKIIα in the laterocapcular division of the central amygdala (CeLC), the conjunctive point between the spinal cord and rostro-ventral medulla. OIH was produced by repeated fentanyl administration in the rat. Correlating with the development of mechanical allodynia and thermal hyperalgesia, CaMKIIα activity was significantly elevated in the CeLC in OIH. In addition, the frequency and amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in CeLC neurons were significantly increased in OIH. 2-[N-(2-hidroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, a CaMKIIα inhibitor, dose dependently reversed sensory hypersensitivity, activation of CeLC CaMKIIα, and mEPSCs in OIH. Taken together, our data for the first time implicate a critical role of CeLC CaMKIIα in OIH. PMID:27451410

  3. Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2.

    Science.gov (United States)

    Liu, Beiying; Qin, Feng

    2016-04-12

    Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia. PMID:27074678

  4. Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats.

    Science.gov (United States)

    Li, Zhi; Zhang, Xiao-Jun; Xu, Hong-xi; Sung, Joseph J Y; Bian, Zhao-xiang

    2009-03-15

    This study aimed to investigate the underlying mechanism of protease-activated receptor-2 (PAR-2) agonist-induced visceral hyperalgesia. Male Sprague-Dawley rat pups were submitted to colonic injection of PAR-2 agonist for 6 consecutive days. The visceral sensitivity to colorectal distention was evaluated by electromyography. The enterochromaffin (EC) cell number, 5-HT content and tryrptophan hydroxylase (TPH) protein expression were detected with immunohistochemistry, fluorescent measurement and Western blot analysis. PAR-2 agonist induced a significant increase of visceral nociceptive response to colorectal distention and a series of neurochemical changes in rat colon, including proliferation of EC cells, increased 5-HT content and enhanced TPH expression. Expression of PAR-2 in EC cells was reported for the first time. Further, selective 5-HT(3) receptor antagonist alosteron significantly inhibited PAR-2-induced visceral hyperalgesia. The enhanced 5-HT signaling is likely responsible for the visceral hyperalgesia induced by PAR-2 agonist. Interruption of this pathway is a possible target for the treatment of visceral hyperalgesia in gastrointestinal diseases. PMID:19374846

  5. TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation

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    Wang Juan

    2011-05-01

    Full Text Available Abstract Background The discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous and noxious heat sensitivity remains in TRPV1 knockout animals. Here we investigated the role of two related channels, TRPV3 and TRPV4, in these capacities. We studied TRPV3 knockout animals on both C57BL6 and 129S6 backgrounds, as well as animals deficient in both TRPV3 and TRPV4 on a C57BL6 background. Additionally, we assessed the contributions of TRPV3 and TRPV4 to acute heat nociception and inflammatory heat hyperalgesia during inhibition of TRPV1. Results TRPV3 knockout mice on the C57BL6 background exhibited no obvious alterations in thermal preference behavior. On the 129S6 background, absence of TRPV3 resulted in a more restrictive range of occupancy centered around cooler floor temperatures. TRPV3 knockout mice showed no deficits in acute heat nociception on either background. Mice deficient in both TRPV3 and TRPV4 on a C57BL6 background showed thermal preference behavior similar to wild-type controls on the thermal gradient, and little or no change in acute heat nociception or inflammatory heat hyperalgesia. Masking of TRPV1 by the TRPV1 antagonist JNJ-17203212 did not reveal differences between C57BL6 animals deficient in TRPV3 and TRPV4, compared to their wild-type counterparts. Conclusions Our results support the notion that TRPV3 and TRPV4 likely make limited and strain-dependent contributions to innocuous warm temperature perception or noxious heat sensation, even when TRPV1 is masked. These findings imply the existence of other significant mechanisms for heat perception.

  6. Caspase Activation of p21-Activated Kinase 2 Occurs During Cisplatin-Induced Apoptosis of SH-SY5Y Neuroblastoma Cells and in SH-SY5Y Cell Culture Models of Alzheimer’s and Parkinson’s Disease

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    Jerry W. Marlin

    2010-04-01

    Full Text Available p21-activated kinase 2 (PAK-2 appears to have a dual function in the regulation of cell survival and cell death. Activation of full-length PAK-2 by the p21 G-proteins Rac or Cdc42 stimulates cell survival. However, PAK-2 is unique among the PAK family because it is also activated through proteolytic cleavage by caspase 3 or similar caspases to generate the constitutively active PAK-2p34 fragment. Caspase activation of PAK-2 correlates with the induction of apoptosis in response to many stimuli and recombinant expression of PAK-2p34 has been shown to stimulate apoptosis in several human cell lines. Here, we show that caspase activation of PAK-2 also occurs during cisplatin-induced apoptosis of SH-SY5Y neuroblastoma cells as well as in SH-SY5Y cell culture models for Alzheimer’s and Parkinson’s disease. Inhibition of mitochondrial complex I or of ubiquitin/proteasome-mediated protein degradation, which both appear to be involved in Parkinson’s disease, induce apoptosis and caspase activation of PAK-2 in SH-SY5Y cells. Overexpression of the amyloid precursor protein, which results in accumulation and aggregation of β-amyloid peptide, the main component of β-amyloid plaques in Alzheimer’s disease, also induces apoptosis and caspase activation of PAK-2 in SH-SY5Y cells. Expression of the PAK-2 regulatory domain inhibits caspase-activated PAK-2p34 and prevents apoptosis in 293T human embryonic kidney cells, indicating that caspase activation of PAK-2 is directly involved in the apoptotic response. This is the first evidence that caspase activation of PAK-2 correlates with apoptosis in cell culture models of Alzheimer’s and Parkinson’s disease and that selective inhibition of caspase-activated PAK-2p34 could prevent apoptosis.

  7. Tratamento farmacológico da hiperalgesia experimentalmente induzida pelo núcleo pulposo Pharmacologic treatment of hyperalgesia experimentally induced by nucleus pulposus

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    André Luiz de Souza Grava

    2010-01-01

    Full Text Available OBJETIVO: Avaliar o efeito de drogas anti-inflamatórias (dexametasona, indometacina, atenolol, indometacina e atenolol e analgésica (morfina sobre a hiperalgesia experimentalmente induzida pelo núcleo pulposo em contato com o gânglio da raiz dorsal de L5. MÉTODOS: Trinta ratos Wistar machos com peso de 220 a 250g foram utilizados no estudo. A indução da hiperalgesia foi realizada por meio do contato de fragmento de núcleo pulposo retirado da região sacrococcígea e colocado sobre o gânglio da raiz dorsal de L5. Os 30 animais foram divididos em grupos experimentais de acordo com a droga utilizada. As drogas foram administradas durante duas semanas a partir da realização do procedimento cirúrgico para a indução da hiperalgesia. A hiperalgesia mecânica e térmica foram avaliadas por meio do teste da pressão constante da pata, von Frey eletrônico e Hargraves por um período de sete semanas. RESULTADOS: A maior redução da hiperalgesia foi observada no grupo de animais tratados pela morfina, seguido pela dexametasona, indometacina e atenolol. A redução da hiperalgesia foi observada após a interrupção da administração das drogas, com exceção do grupo de animais tratados com morfina, nos quais ocorreu aumento da hiperalgesia após a interrupção do tratamento. CONCLUSÕES: A hiperalgesia induzida pelo contato do núcleo pulposo com o gânglio da raiz dorsal pode ser reduzida com a administração de anti-inflamatórios e analgésicos, tendo sido observado a maior redução da hiperalgesia com a administração da morfina e dexametasona.OBJECTIVE: To evaluate the effect of antiinflammatory (dexamethasone, indomethacin, atenolol, indomethacin and atenolol and analgesic drugs (morphine on hyperalgesia experimentally induced by nucleus pulposus (NP contact with the L5- dorsal root ganglion (DRG. METHODS: Thirty male Wistar rats with weights ranging from 220 to 250 g were used in the study. The hyperalgesia was induced by

  8. Co-induction of cyclooxyenase-2 and early growth response gene (Egr-1 in spinal cord in a clinical model of persistent inflammation and hyperalgesia

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    Dolan Sharron

    2011-11-01

    Full Text Available Abstract Background This study characterised the effects of persistent peripheral inflammation of the foot on pain and spinal cord expression of cyclooxygenase-1 and -2 (COX-1 and COX-2 and early growth response gene 1 (Egr-1, known markers of neuronal plasticity, in a clinical model of naturally-occurring inflammatory disease and hyperalgesia in sheep ('footrot', before and after routine treatment (parenteral treatment with antibiotics and antiseptic footbathing. The temporal pattern of expression of COX-1, COX-2 and Egr-1 mRNA and protein were analysed using real-time PCR and Western blotting. Results Animals affected with persistent peripheral inflammation displayed significant hyperalgesia and lameness (a proxy indicator of spontaneous pain restricted to the inflamed limb. Hyperalgesia and lameness were significantly attenuated 1 day after treatment, and resolved further by day 7 and day 3, respectively. COX-2 but not COX-1, protein expression was up-regulated in spinal cord from lame animals on day 0, before treatment. Following treatment and attenuation of pain behaviours, levels of COX-2 returned to control levels. Significant induction of Egr-1 mRNA and protein were observed in spinal cord from lame animals. Three days after treatment, levels of Egr-1 mRNA returned to control levels, however, Egr-1 protein remained elevated. Conclusion Elevated levels of spinal COX-2 and Egr-1 protein correlate with the presence of pain and hyperalgesia, and may underlie persistent pain, although a direct causal link has still to be established. Understanding the temporal pattern of expression of key mediators in clinical pain states may lead to better strategies to manage pain.

  9. Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder

    OpenAIRE

    Lai, H. Henry; Qiu, Chang-Shen; Crock, Lara W.; Morales, Maria Elena P.; Ness, Tim J.; Gereau, Robert W.

    2011-01-01

    Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord following innocuous and noxious distention of the inflamed (cyclophosphamide- treated) and non-inflamed uri...

  10. Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons.

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    Masaya Watanabe

    Full Text Available The Cav3.2 isoform of the T-type calcium channel is expressed in primary sensory neurons of the dorsal root ganglion (DRG, and these channels contribute to nociceptive and neuropathic pain in rats. However, there are conflicting reports on the roles of these channels in pain processing in rats and mice. In addition, the function of T-type channels in persistent inflammatory hyperalgesia is poorly understood. We performed behavioral and comprehensive histochemical analyses to characterize Cav3.2-expressing DRG neurons and examined the regulation of T-type channels in DRGs from C57BL/6 mice with carrageenan-induced inflammatory hyperalgesia. We show that approximately 20% of mouse DRG neurons express Cav3.2 mRNA and protein. The size of the majority of Cav3.2-positive DRG neurons (69 ± 8% ranged from 300 to 700 μm2 in cross-sectional area and 20 to 30 μm in estimated diameter. These channels co-localized with either neurofilament-H (NF-H or peripherin. The peripherin-positive cells also overlapped with neurons that were positive for isolectin B4 (IB4 and calcitonin gene-related peptide (CGRP but were distinct from transient receptor potential vanilloid 1 (TRPV1-positive neurons during normal mouse states. In mice with carrageenan-induced inflammatory hyperalgesia, Cav3.2 channels, but not Cav3.1 or Cav3.3 channels, were upregulated in ipsilateral DRG neurons during the sub-acute phase. The increased Cav3.2 expression partially resulted from an increased number of Cav3.2-immunoreactive neurons; this increase in number was particularly significant for TRPV1-positive neurons. Finally, preceding and periodic intraplantar treatment with the T-type calcium channel blockers mibefradil and NNC 55-0396 markedly reduced and reversed mechanical hyperalgesia during the acute and sub-acute phases, respectively, in mice. These data suggest that Cav3.2 T-type channels participate in the development of inflammatory hyperalgesia, and this channel might play an

  11. Warming Moxibustion Relieves Chronic Visceral Hyperalgesia in Rats: Relations to Spinal Dynorphin and Orphanin-FQ System

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    Li Qi

    2013-01-01

    Full Text Available As a twin therapy of acupuncture in traditional Chinese medicine, moxibustion has shown its effects in relieving abdominal pain in irritable bowel syndrome (IBS patients and IBS rat models, but its mechanisms are largely unknown. In this paper, we determined the role of spinal dynorphin and orphanin-FQ system in analgesic effect of warming moxibustion (WM on chronic visceral hyperalgesia (CVH in IBS-like rat model. Here, we show that (1 repeated WM at bilateral ST25 and ST37 acupoints markedly attenuated the abdominal withdrawal reflex scores in CVH rats; (2 intrathecal administration of κ receptor antagonist prior to WM significantly attenuated the WM analgesia and dynorphinA (1-17 enhanced the WM analgesia. WM significantly reinforced the upregulation of spinal dynorphin mRNA/protein and κ receptor mRNA levels in CVH rats; (3 intrathecal administration of orphanin-FQ receptor antagonist prior to WM significantly attenuated the WM analgesia and orphanin-FQ enhanced the WM analgesia. WM reinforced the upregulation of spinal orphanin-FQ mRNA/protein and orphanin-FQ receptor mRNA levels in CVH rats. These results suggest that moxibustion may relieve CVH at least in part by activating spinal dynorphin and orphanin-FQ system.

  12. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Cotrim, Ana P. [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yoshikawa, Masanobu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa (Japan); Sunshine, Abraham N.; Zheng Changyu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2012-07-15

    Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

  13. Cisplatin-induced Casepase-3 activation in different tumor cells

    Science.gov (United States)

    Shi, Hua; Li, Xiao; Su, Ting; Zhang, Yu-Hai

    2008-12-01

    Apoptosis plays an essential role in normal organism development which is one of the main types of programmed cell death to help tissues maintain homeostasis. Defective apoptosis can result in cell accumulation and therefore effects on tumor pathogenesis, progression and therapy resistance. A family of proteins, known as caspases, is typically activated in the early stages of apoptosis. Therefore, studying the kinetics of activation of caspases induced by antitumor drugs can contribute to antitumor drug discovery and explanation of the molecular mechanisms. This paper detected the Caspase-3 activity induced by cisplatin in human adenoid cystic carcinoma cell line (ACC-M), human hepatocellular liver carcinoma cell line (HepG2) and human epithelial carcinoma cell line (Hela) with stably expressing ECFP-DEVDDsRed (CD3) probe, a fluorescent probe consisting of Enhanced Cyan Fluorescent Protein (ECFP), red fluorescent protein (DsRed) and a linker with a recognition site of Caspase-3, by using the capillary electrophoresis (CE) and fluorescence resonance energy transfer (FRET) imaging system. Under the same concentration of cisplatin, ACC-M cells responded the most rapidly, and then HepG2 cells and Hela cells, respectively, in the early 30 hours. Later, HepG2 cells represented acceleration in the Caspase-3 activation speed and reached full activation the earliest comparing to other two cell types. The results demonstrated that ACC-M cell is more sensitive than the other two cell types under the treatment of cisplatin.

  14. Cisplatin-induced downregulation of OCTN2 affects carnitine wasting

    OpenAIRE

    Lancaster, Cynthia; Hu, Chaoxin; Franke, Ryan; Filipski, Kelly; Orwick, S.J.; Chen, Zhaoyuan; Zuo, Zhili; Loos, Walter; Sparreboom, Alex

    2010-01-01

    textabstractPurpose: Carnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function. Experimental Design: Excretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration. The transport of carnitine was assessed ...

  15. Sappanone A protects mice against cisplatin-induced kidney injury.

    Science.gov (United States)

    Kang, Lin; Zhao, Huanfen; Chen, Chen; Zhang, Xiuzhi; Xu, Mingtang; Duan, Huijun

    2016-09-01

    Cisplatin (CP) is an anti-cancer drug that often causes nephrotoxicity due to enhanced inflammatory response and oxidative stress. Sappanone A (SA), a homoisoflavanone isolated from the heartwood of Caesalpinia sappan, has been known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the protective effects and mechanism of SA on CP-induced kidney injury in mice. The results showed that treatment of SA improved CP-induced histopathalogical injury and renal dysfunction. SA also inhibited CP-induced MPO, MDA, TNF-α and IL-1β production and up-regulated the activities of SOD and GSH-PX decreased by CP. SA significantly inhibited the apoptosis rate of kidney tissues induced by CP. Furthermore, SA was found to inhibit CP-induced NF-κB activation. Treatment of SA up-regulated the expression of Nrf2 and HO-1 in a dose-dependent manner. In vitro, SA dose-dependently inhibited CP-induced TNF-α and IL-1β production and NF-κB activation in HK-2 cells. In conclusion, these results suggested that SA inhibited CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation. SA was a potential therapeutic drug for treating CP-induced kidney injury. PMID:27318179

  16. Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

    International Nuclear Information System (INIS)

    Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. Methods and Materials: Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

  17. Genetic risk factors of cisplatin induced ototoxicity in adult patients.

    Science.gov (United States)

    Talach, T; Rottenberg, J; Gal, B; Kostrica, R; Jurajda, M; Kocak, I; Lakomy, R; Vogazianos, E

    2016-01-01

    Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001). PMID:26774148

  18. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  19. Real-time monitoring of cisplatin-induced cell death.

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    Hamed Alborzinia

    Full Text Available Since the discovery of cisplatin more than 40 years ago and its clinical introduction in the 1970s an enormous amount of research has gone into elucidating the mechanism of action of cisplatin on tumor cells. With a novel cell biosensor chip system allowing continuous monitoring of respiration, glycolysis, and impedance we followed cisplatin treatment of different cancer cell lines in real-time. Our measurements reveal a first effect on respiration, in all cisplatin treated cell lines, followed with a significant delay by interference with glycolysis in HT-29, HCT-116, HepG2, and MCF-7 cells but not in the cisplatin-resistant cell line MDA-MB-231. Most strikingly, cell death started in all cisplatin-sensitive cell lines within 8 to 11 h of treatment, indicating a clear time frame from exposure, first response to cisplatin lesions, to cell fate decision. The time points of most significant changes were selected for more detailed analysis of cisplatin response in the breast cancer cell line MCF-7. Phosphorylation of selected signal transduction mediators connected with cellular proliferation, as well as changes in gene expression, were analyzed in samples obtained directly from sensor chips at the time points when changes in glycolysis and impedance occurred. Our online cell biosensor measurements reveal for the first time the time scale of metabolic response until onset of cell death under cisplatin treatment, which is in good agreement with models of p53-mediated cell fate decision.

  20. Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

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    Wen Yeong-Ray

    2010-10-01

    Full Text Available Abstract Background Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood. Results A decrease in paw withdrawal latency (PWL after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1 and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK activity after reinflammation. Conclusions Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.

  1. Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord.

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    Kenji W Ruiz-Miyazawa

    Full Text Available Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH levels, superoxide anion, tumor necrosis factor alpha (TNF-α and interleukin 1 beta (IL-1β levels, as well as nuclear factor kappa B (NF-κB activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases, as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

  2. Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

    Science.gov (United States)

    Ruiz-Miyazawa, Kenji W.; Zarpelon, Ana C.; Pinho-Ribeiro, Felipe A.; Pavão-de-Souza, Gabriela F.; Casagrande, Rubia; Verri, Waldiceu A.

    2015-01-01

    Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels. PMID:25822523

  3. Exercise preconditioning reduces neonatal incision surgery-induced enhanced hyperalgesia via inhibition of P38 mitogen-activated protein kinase and IL-1β, TNF-α release.

    Science.gov (United States)

    Gong, Xingrui; Jiang, Jing; Zhang, Mazhong

    2016-08-01

    Neonatal surgery leads to enhanced hyperalgesia to noxious stimulation in adulthood via a mechanism caused by enhanced phosphorylated (p)-p38 expression in microglia. We tested the effect of exercise on reducing enhanced hypersensitivity primed by neonatal incision surgery. Adult female Wistar rats, with or without neonatal incision surgery at postnatal day (P) 3, received right hind paw plantar incision surgery under anesthesia at P44. The rats performed wheel-running exercise from P22 to P41. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured and ipsilateral spinal cords were collected for protein quantification. For PWT and PWL, exercise reduced the pain index after incision surgery at P44 in rats with neonatal surgery (Pexercise suppressed P-p38 expression relative to adult rats without neonatal surgery (Pexercise reduced IL-1β and TNF-α (PExercise preconditioning is an effective approach to reducing enhanced adult hyperalgesia primed by neonatal surgery. The mechanism may be explained by exercise-induced inhibition of P-p38 activation and IL-1β, TNF-α release. PMID:27235543

  4. The Relationship between Mechanical Hyperalgesia Assessed by Manual Tender Point Examination and Disease Severity in Patients with Chronic Widespread Pain: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Kirstine Amris

    2014-01-01

    Full Text Available The clinical utility of tender point (TP examination in patients reporting chronic widespread pain (CWP is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a large number of disease variables became consistently significant explanatory factors, whereas none of the disease variables reached a significance level in the continuum model. These results support the premise that the presence of mechanical hyperalgesia influences symptomatology in CWP and that the severity of clinical expression is related to a threshold of TPs, rather than being part of a continuum.

  5. 鸡矢藤注射液和野木瓜注射液对大鼠足底皮下化学组织损伤诱致自发痛、痛敏和炎症的作用%Effects of intravenous Injections Paederiae and Stauntonia on spontaneous pain, hyperalgesia and inflammation induced by cutaneous chemical tissue injury in the rat

    Institute of Scientific and Technical Information of China (English)

    彭小莉; 高喜玲; 陈军; 黄熙; 陈会生

    2003-01-01

    -induced persistent spontaneous pain-related responses ( PSPR), primary thermal/mechanical hyperalgesia and inflammation in conscious rats. Injection of bee venom ( BV, 0.1 mg, 50 μl) into the plantar surface of one hind paw resulted in not only a 1-h monophasic PSPR such as flinching reflex in the injected paw and a subsequent period of 3 -4 days primary heat and mechanical hyperalgesia, but also a marked sign of inflammation, including redness and swelling of the plantar surface in the injected paw. Intraplantar injection of formalin produced two phases of PSPR as reported previously. Systemic pre-treatment with three doses of IP (0. 32, 1.6 and 9.0ml/kg, 500% ) or IS (0.32, 1.6 and 9.0 ml/kg, 250% ) produced a dose-dependent suppression of the BV- or formalin-induced flinching reflex of 1 h time course as compared with the saline control group. Post-treatment with IP or IS 5 min after BV injection also produced a significant suppression of the flinching reflex in both BV test and formalin test respectively, as compared with the control group. However, neither pre- nor post-treatment with IP or IS produced any significantly suppressive effect on the BV-induced primary heat and mechanical hyperalgesia and inflammation. The analgesia produced by IP or IS was not mediated by the endogenous opioid receptors since naloxone, a non-selective opioid receptor antagonist, had no reversal effect on the IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest that IP or IS might prevent and relieve clinical persistent spontaneous pain, but without any anti-nociceptive and anti-inflammatory effects on the primary heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses. The BV test might be a useful model of pain to evaluate and screen anti-nociceptive and anti-inflammatory effects of certain compounds of the Chinese medicinal herbs on the pathological origins of pain.

  6. P2X₇ receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

    Science.gov (United States)

    Liu, Shuangmei; Shi, Qingming; Zhu, Qicheng; Zou, Ting; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Wu, Qin; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Lv, Qiulan; Zou, Lifang; Zhang, Xi; Ying, Mofeng; Li, Guodong; Liang, Shangdong

    2015-06-01

    Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor. PMID:25527178

  7. 鞘内注射孤啡肽对大鼠足底注入蜜蜂毒诱致长时程自发痛、痛敏和炎症的不同效果%Differential actions of intrathecal nociceptin on persistent spontaneous nociception, hyperalgesia and inflammation produced by subcutaneous bee venom injection in conscious rats

    Institute of Scientific and Technical Information of China (English)

    孙焱芫; 罗层; 李震; 陈军

    2004-01-01

    为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用.结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30 nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6and57±11%(三个剂量vs对照,P<0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响.CompB(30 nmo1)可完全翻转10 nmol孤啡肽对自发缩足反射的抑制作用.鞘内单次或重复注射孤啡肽(10 nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用.本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响.%Nociceptin is an endogenous ligand for the opioid receptor-like 1 (ORL1) receptor. The present study was designed to investigate spinal actions of nociceptin on the spontaneous nociception, hyperalgesia and inflammation induced by subcutaneous bee venom injection.Subcutaneous injection of bee venom into one hindpaw of conscious rat produced a persistent spontaneous nociception followed by a longlasting primary heat and mechanical hyperalgesia as well as local inflammation. Compared with the pre-saline group, pretreatment with intrathecal injection of three doses (3, 10 and 30 nmol) of nociceptin produced significant suppression on the spontaneous paw flinching reflex.The inhibitory rates were 37 ± 7, 43±6 and 57 ± 11%, respectively, which were enhanced with an increase in the concentration of nociceptin

  8. District heating

    International Nuclear Information System (INIS)

    The papers presented at this meeting dealt with an international comparison of district heating, the Swiss district heating network, political aspects of nuclear district heating, nuclear and non-nuclear sources for district heating. 17 figs., 6 tabs

  9. Heat Waves

    Science.gov (United States)

    Heat Waves Dangers we face during periods of very high temperatures include: Heat cramps: These are muscular pains and spasms due ... that the body is having trouble with the heat. If a heat wave is predicted or happening… - ...

  10. Antinociceptive Effect of Vardenafil on Carrageenan-Induced Hyperalgesia in Rat: involvement of Nitric Oxide/Cyclic Guanosine Monophosphate/Calcium Channels Pathway.

    Science.gov (United States)

    Gediz, Ezgi İkiz; Nacitarhan, Cahit; Minareci, Edibe; Sadan, Gulay

    2015-01-01

    In this study, we aimed to investigate the peripheral antinociception effects of specific phosphodiesterase 5 (PDE-5) inhibitor vardenafil on carrageenan-induced nociception in rats, and the role of calcium besides the L-arginine- nitric oxide (NO)- cyclic guanosine monophophate (cGMP) pathway in these effects. Hyperalgesia was induced by the intraplantar injection of 0.1 mL fresh carrageenan solution to right hind-paw whereas, saline as a vehicle of carrageenan was injected to the left paw. This procedure was used for measuring mechanic nociception pressure via an analgesimeter. Pressure which produced nociception was measured before (0 minute) and after(15, 30, 60 and 120 minutes) carrageenan injection. Local administration of vardenafil produced a dose-dependent antinociceptive effect. Pretreatment with N(W)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), oxadiazolo (4, 3, a) quinoxalin -1-one (ODQ, inhibitor of guanylyl cyclase) or A23187 (calcium ionophore) decreased the effect of vardenafil. In contrast, L-arginine (nitric oxide donor) seemed to potentiate the vardenafil-induced antinociception. Our results suggest that phosphodiesterase type-5 inhibitor vardenafil may offer a new therapeutic tool to treat pain. It's effect was probably result from L-arginine/NO-cGMP pathway activation and Ca + 2 channels are also involved. PMID:26664380

  11. Induction of Hyperalgesia in Pigs through Blocking Low Hydraulic Resistance Channels and Reduction of the Resistance through Acupuncture: A Mechanism of Action of Acupuncture

    Directory of Open Access Journals (Sweden)

    Wei-Bo Zhang

    2013-01-01

    Full Text Available According to the classic theory of Chinese medicine, pain is due to the blockage in meridian channels, and acupuncture was invented to treat pain by “dredging” the channels. To test the theory, a hyperalgesia model was made by injecting hydrogel into low hydraulic resistance channel (LHRC in 12 anaesthetized minipigs. Tail-flick threshold and ear-flick threshold were measured using a thermal radiation dolorimeter, and relative flick threshold (RFT was calculated. Hydraulic resistance (HR was measured with a biological HR measuring instrument on low HR points on LHRC and on control points with higher HR located outside LHRC; readings were recorded before, during, and after acupuncture treatment. RFT decreased after blocking the LRHC and was still significantly decreased 2 days and 4 days afterwards. No significant changes occurred when injecting saline into the same points or injecting gel into points outside the channel. Subsequent acupuncture reduced HR on LRHC along meridians but had no significant effect on sites with higher HR located outside LHRC. One of the mechanisms of action of acupuncture treatment for chronic pain may be that acupuncture affects peripheral tissue by reducing the HR in LHRC along meridians, improving the flow of interstitial fluid and removing algogenic substances and thereby relieving pain.

  12. Peripheral G protein-coupled inwardly rectifying potassium (GIRK) channels are involved in delta opioid receptor-mediated anti-hyperalgesia in rat masseter muscle

    Science.gov (United States)

    Chung, Man-Kyo; Cho, Yi Sul; Bae, Young Chul; Lee, Jongseok; Zhang, Xia; Ro, Jin Y.

    2014-01-01

    Background Although the efficacy of peripherally administered opioid has been demonstrated in preclinical and clinical studies, the underlying mechanisms of its anti-hyperalgesic effects are poorly understood. G protein-coupled inwardly rectifying potassium (GIRK) channels are linked to opioid receptors in the brain. However, the role of peripheral GIRK channels in analgesia induced by peripherally administered opioid, especially in trigeminal system, is not clear. Methods Expression of GIRK subunits in rat trigeminal ganglia (TG) was examined with RT-PCR, western blot and immunohistochemistry. Chemical profiles of GIRK expressing neurons in TG were further characterized. Behavioral and Fos experiments were performed to examine the functional involvement of GIRK channels in delta opioid receptor (DOR)-mediated anti-hyperalgesia under an acute myositis condition. Results TG expressed mRNA and proteins for GIRK1 and GIRK2 subunits. Majority of GIRK1- and GIRK2-expressing neurons were non-peptidergic afferents. Inhibition of peripheral GIRK using Tertiapin-Q (TPQ) attenuated anti-nociceptive effects of peripherally administered DOR agonist, DPDPE, on mechanical hypersensitivity in masseter muscle. Furthermore, TPQ attenuated the suppressive effects of peripheral DPDPE on neuronal activation in the subnucleus caudalis of the trigeminal nucleus (Vc) following masseteric injection of capsaicin. Conclusions Our data indicate that peripheral DOR agonist-induced suppression of mechanical hypersensitivity in the masseter muscle involves the activity of peripheral GIRK channels. These results could provide a rationale for developing a novel therapeutic approach using peripheral GIRK channel openers to mimic or supplement the effects of peripheral opioid agonist. PMID:23740773

  13. Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia

    Directory of Open Access Journals (Sweden)

    Kobayashi Kimiko

    2008-04-01

    Full Text Available Abstract Background Honeybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK in the generation of BV-induced pain hypersensitivity. Results We found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38 was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn. Conclusion The results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.

  14. Heat Stress

    Science.gov (United States)

    ... Publications and Products Programs Contact NIOSH NIOSH HEAT STRESS Recommend on Facebook Tweet Share Compartir NEW Criteria ... hot environments may be at risk of heat stress. Exposure to extreme heat can result in occupational ...

  15. Prediction of postoperative pain by preoperative nociceptive responses to heat stimulation

    DEFF Research Database (Denmark)

    Werner, Mads U; Duun, Preben; Kehlet, Henrik

    2004-01-01

    with development of significant hyperalgesia. There was a significant correlation between preoperative pain ratings during the burn injury and early (0-2 days, area under the curve) and late (3-10 days, area under the curve) postoperative dynamic pain ratings during limb movement. CONCLUSION: The......BACKGROUND: Despite major advances in the understanding of the neurobiologic mechanisms of pain, the wide variation in acute pain experience has not been well explained. Therefore, the authors investigated the potential of a preoperatively induced heat injury to predict subsequent postoperative...... results of this study suggest that the pain response to a preoperative heat injury may be useful in research in predicting the intensity of postoperative pain. These findings may have important implications to identify patients at risk for development of chronic pain and to stratify individuals for...

  16. Heat pumps

    CERN Document Server

    Macmichael, DBA

    1988-01-01

    A fully revised and extended account of the design, manufacture and use of heat pumps in both industrial and domestic applications. Topics covered include a detailed description of the various heat pump cycles, the components of a heat pump system - drive, compressor, heat exchangers etc., and the more practical considerations to be taken into account in their selection.

  17. Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

    Directory of Open Access Journals (Sweden)

    Masocha Willias

    2010-12-01

    Full Text Available Abstract Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p. to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg had no significant activity, minocycline (25 to 100 mg/kg produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg and a selective COX-2 inhibitor, CAY10404 (10 mg/kg had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg or minocycline (50 mg/kg did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH limb paw pressure ratios and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg or

  18. Heat pumps

    CERN Document Server

    Brodowicz, Kazimierz; Wyszynski, M L; Wyszynski

    2013-01-01

    Heat pumps and related technology are in widespread use in industrial processes and installations. This book presents a unified, comprehensive and systematic treatment of the design and operation of both compression and sorption heat pumps. Heat pump thermodynamics, the choice of working fluid and the characteristics of low temperature heat sources and their application to heat pumps are covered in detail.Economic aspects are discussed and the extensive use of the exergy concept in evaluating performance of heat pumps is a unique feature of the book. The thermodynamic and chemical properties o

  19. Heat Pipes

    Science.gov (United States)

    1996-01-01

    Heat Pipes were originally developed by NASA and the Los Alamos Scientific Laboratory during the 1960s to dissipate excessive heat build- up in critical areas of spacecraft and maintain even temperatures of satellites. Heat pipes are tubular devices where a working fluid alternately evaporates and condenses, transferring heat from one region of the tube to another. KONA Corporation refined and applied the same technology to solve complex heating requirements of hot runner systems in injection molds. KONA Hot Runner Systems are used throughout the plastics industry for products ranging in size from tiny medical devices to large single cavity automobile bumpers and instrument panels.

  20. Heat management

    International Nuclear Information System (INIS)

    The conference was based on the Heat Management Ordinance of December 1991 which requires the establishment of heat use concepts for many plants that are subject to licensing. For an industrial enterprises, a good heat use concept is also an energy concept. The papers and discussions of the conference discussed the practical implementation of the Heat Management Ordinance in industrial enterprises and the consequences for licensing practice. Examples of specific plants were presented. The 16 conference papers are available as separate entries on this database. (orig./HP)

  1. Heat pipes

    CERN Document Server

    Dunn, Peter D

    1994-01-01

    It is approximately 10 years since the Third Edition of Heat Pipes was published and the text is now established as the standard work on the subject. This new edition has been extensively updated, with revisions to most chapters. The introduction of new working fluids and extended life test data have been taken into account in chapter 3. A number of new types of heat pipes have become popular, and others have proved less effective. This is reflected in the contents of chapter 5. Heat pipes are employed in a wide range of applications, including electronics cooling, diecasting and injection mo

  2. Magnetar heating

    CERN Document Server

    Beloborodov, Andrei M

    2016-01-01

    We examine four candidate mechanisms that could explain the high surface temperatures of magnetars. (1) Heat flux from the liquid core heated by ambipolar diffusion. It could sustain the observed surface luminosity $L_s\\approx 10^{35}$ erg s$^{-1}$ if core heating offsets neutrino cooling at a temperature $T_{\\rm core}>6\\times 10^8$ K. This scenario is viable if the core magnetic field exceeds $10^{16}$ G, the magnetar has mass $M10^{16}$ G varying on a 100 meter scale could provide $L_s\\approx 10^{35}$ erg s$^{-1}$. (4) Bombardment of the stellar surface by particles accelerated in the magnetosphere. This mechanism produces hot spots on magnetars. Observations of transient magnetars show evidence for external heating.

  3. Attenuation of cisplatin induced ototoxicity by sound preonditioning through NO pathway

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective:To explore the protective effect of sound preconditioning against ototoxicity induced by cisplatin and its possible mechanism with respect to the nitric oxide (NO) pathway. Methods:Albino guinea pigs were divided into silent control, CDDP,sound preconditioning and sound preconditioning+CDDP groups. The animals of the CDDP group were injected with cisplatin intravenously 8 mg/kg b.w. The animals in the sound preconditioning were exposed to white noise at 85dB SPL, 5h/d, for 10 d (sound preconditioning). The animals in the sound preconditioning+CDDP group were treated with sound preconditioning first and then administrated with cisplatin intravenously 8 mg/kg b.w. Hearing thresholds of auditory brainstem responses (ABRs) of all animals were measured to evaluate hearing function. Hair cell loss was estimated via surface preparation. Cochlear tissue was assayed for measurement of NO level and immunohistochemistry method was used for inducible nitric oxide synthase (iNOS) analysis. Results:There was no significant difference between the silent control and sound preconditioning animals with respect to either functional or histological measures. Among the animals in the CDDP group, there was a significant elevation of threshold at the high test frequencies after administration compared with the silent control group (P<0.05). Morphological examination showed that there was obvious loss of the OHC, especially in the third row of the basal turn. The NO level and immunoreactivity to iNOS in this group were higher and more intensive than those of the silent control group (P<0.05). The ABR thresholds in the sound preconditioning + CDDP group were much lower than those of the CDDP group (P<0.05). Slight sporadic loss of OHC was found in this group. The immunoreactivity to iNOS and the level of NO in cochlea decreased significantly compared with the CDDP group (P<0. 05). Conclusion:It is suggested that sound preconditioning, to some extent, provides protective effect against ototoxicity of cisplatin. The excess synthesis of NO induced by the over-expressed of iNOS may be involved in the CDDP induced ototoxicity. The possible mechanism is related to suppression of the NO pathway.

  4. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

    Science.gov (United States)

    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. PMID:26522737

  5. Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Kim, Tae-Won; Song, In-Bae; Lee, Hong-Ki; Lim, Jong-Hwan; Cho, Eun-Sang; Son, Hwa-Young; Park, Sang-Jin; Kim, Jong-Woo; Yun, Hyo-In

    2012-12-01

    Platycodin D (PD) is well known as a potent triterpenoid saponin having various pharmacological activities isolated from the root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5 mg/kg) treated group. PD was given for three consecutive days before CDDP injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in CDDP alone treated mice were decreased to normal range by pretreatment with PD. It also decreased nitric oxide (NO) and lipid peroxidation with increased antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in PD pretreated mice. In histopathological examination, pretreatment with PD showed ameliorated renal injury such as intraluminal cast formation and epithelial desquamation. Furthermore, over-expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP-induced nephrotoxicity. PMID:22617354

  6. Cisplatin-induced ototoxicity : Morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?

    NARCIS (Netherlands)

    Cardinaal, RM; de Groot, JCMJ; Huizing, EH; Veldman, JE; Smoorenburg, GF

    2000-01-01

    Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infr

  7. C-phycocyanin prevents cisplatin-induced mitochondrial dysfunction and oxidative stress.

    Science.gov (United States)

    Fernández-Rojas, Berenice; Rodríguez-Rangel, Daniela Sarai; Granados-Castro, Luis Fernando; Negrette-Guzmán, Mario; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Molina-Jijón, Eduardo; Reyes, José L; Zazueta, Cecilia; Pedraza-Chaverri, José

    2015-08-01

    The potential of C-phycocyanin (C-PC) to prevent cisplatin (CP)-induced kidney mitochondrial dysfunction was determined in CD-1 male mice. The CP-induced mitochondrial dysfunction was characterized by ultrastructural abnormalities and by decrease in the following parameters in isolated kidney mitochondria: adenosine diphosphate (ADP)-induced oxygen consumption (state 3), respiratory control ratio, ADP/oxygen (ADP/O) ratio, adenosine triphosphate synthesis, membrane potential, calcium retention, glutathione (GSH) content, and activity of respiratory complex I, aconitase, catalase, and GSH peroxidase. These mitochondria also showed increase in hydrogen peroxide production, malondialdehyde, and 3-nitrotyrosine protein adducts content. The above-described changes, as well as CP-induced nephrotoxicity, were attenuated in mice pretreated with a single injection of C-PC. Our data suggest that the attenuation of mitochondrial abnormalities is involved in the protective effect of C-PC against CP-induced nephrotoxicity. This is the first demonstration that C-PC pretreatment prevents CP-induced mitochondrial dysfunction in mice. PMID:25971372

  8. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer12

    OpenAIRE

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A.; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I.; Roesler, Rafael; Jacques E Nör

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we...

  9. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    OpenAIRE

    Carolina Nör; Zhaocheng Zhang; Warner, Kristy A.; Lisiane Bernardi; Fernanda Visioli; Helman, Joseph I.; Rafael Roesler; Jacques E Nör

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we...

  10. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2014-01-01

    Full Text Available Cisplatin (CisPt is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.

  11. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yafei [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Brott, David [Patient Safety, AstraZeneca R and D Wilmington, DE 19850 (United States); Luo, Wenli [Discovery Statistics, AstraZeneca R and D Waltham, MA 02451 (United States); Gangl, Eric [DMPK, AstraZeneca R and D Waltham, MA 02451 (United States); Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Valentin, Jean-Pierre [Global Safety Assessment, AstraZeneca R and D Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States)

    2013-05-01

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.

  12. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    International Nuclear Information System (INIS)

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development

  13. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Cetin, Damla; Hacımuftuoglu, Ahmet; Tatar, Abdulgani; Turkez, Hasan; Togar, Basak

    2016-08-01

    Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro. PMID:26199062

  14. Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Bolisetty, Subhashini; Traylor, Amie; Joseph, Reny; Zarjou, Abolfazl; Agarwal, Anupam

    2016-03-01

    Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. The beneficial effects of HO-1 expression are not merely due to degradation of the pro-oxidant heme but are also credited to the by-products that have potent, protective effects, including antioxidant, anti-inflammatory, and prosurvival properties. This is well reflected in the preclinical animal models of injury in both renal and nonrenal settings. However, excessive accumulation of the by-products can be deleterious and lead to mitochondrial toxicity and oxidative stress. Therefore, use of the HO system in alleviating injury merits a targeted approach. Based on the higher susceptibility of the proximal tubule segment of the nephron to injury, we generated transgenic mice using cre-lox technology to enable manipulation of HO-1 (deletion or overexpression) in a cell-specific manner. We demonstrate the validity and feasibility of these mice by breeding them with proximal tubule-specific Cre transgenic mice. Similar to previous reports using chemical modulators and global transgenic mice, we demonstrate that whereas deletion of HO-1, specifically in the proximal tubules, aggravates structural and functional damage during cisplatin nephrotoxicity, selective overexpression of HO-1 in proximal tubules is protective. At the cellular level, cleaved caspase-3 expression, a marker of apoptosis, and p38 signaling were modulated by HO-1. Use of these transgenic mice will aid in the evaluation of the effects of cell-specific HO-1 expression in response to injury and assist in the generation of targeted approaches that will enhance recovery with reduced, unwarranted adverse effects. PMID:26672618

  15. The effect of Ginkgo extract EGb761 in cisplatin-induced peripheral neuropathy in mice

    International Nuclear Information System (INIS)

    Neuroprotective effect of Ginkgo biloba extract EGb761 in cisplatin (cis-diamminedi-chloroplatinum, or CDDP)-induced peripheral neuropathy was investigated. Swiss albino mice were treated with CDDP, 2 mg/kg ip twice a week for nine times. One group of the animals also received EGb761 in the drinking water at an estimated dosage of 100 mg/kg per day. Two other groups received vehicle (control) or EGb761 only. Development of neuropathy was evaluated with changes in sensory nerve conduction velocity (NCV). Following the treatments, dorsal root ganglia (DRGs) were microscopically examined and some were cultured for 3 days. EGb761 proved effective in preventing the reduction in NCV (P < 0.0001) caused by CDDP. CDDP caused a decrease in the number of migrating cells (P < 0.01) and in the length of outgrowing axons (P < 0.01) while EGb761 treatment prevented the latter. CDDP led to smaller nuclear and somatic sizes in neurons (P < 0.01), while with EGb761 co-administration, both were close to control values. Animals having EGb761 only had similar results with controls. In conclusion, EGb761 was found to be effective in preventing some functional and morphological deteriorations in CDDP-induced peripheral neuropathy

  16. Possible Protective Effect of Sertraline against Cisplatin-Induced Ototoxicity: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Murat Ozturk

    2013-01-01

    Full Text Available Background/Objective. Cisplatin is a widely used chemotherapeutic agent, but its ototoxicity side effect can occur in the majority of patients. Lots of agents were tried to prevent this, but there is not a routine treatment modality yet. The aim of this study was to evaluate the otoprotective effect of sertraline, which is an antidepressant with neuroprotective effects, against cisplatin, in rats. Design. Experimental animal study. Material and Methods. Forty-eight rats were randomly separated in two groups as groups I and II. Group I was identified as the control group and only a single dose of intraperitoneal cisplatin was administered. In group II, in addition to cisplatin, sertraline was administered to the rats through an oral cannula for ten-day period. Distortion product otoacoustic emission measurements were performed at the first day and the 10th day. Results. When the ototoxicity rates after cisplatin in group I and group II in distortion product otoacoustic emission measurements were compared, it was statistically significantly lower in group II in frequencies of 5652, 6165, 6726, 7336, and 7996 Hz (. Conclusion. Sertraline seems to have a protective effect on cisplatin ototoxicity and could be used to prevent the ototoxicity and also to treat the depression that occurred in cancer patients together.

  17. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer

    Directory of Open Access Journals (Sweden)

    Tomohiko Sasaki

    2016-01-01

    Conclusion: Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure.

  18. Voluntary Exercise Prevents Cisplatin-Induced Muscle Wasting during Chemotherapy in Mice

    OpenAIRE

    Pernille Hojman; Jonas Fjelbye; Bo Zerahn; Jesper F Christensen; Christine Dethlefsen; Lonkvist, Camilla K.; Claus Brandt; Hanne Gissel; Bente Klarlund Pedersen; Julie Gehl

    2014-01-01

    Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatm...

  19. Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

    OpenAIRE

    Choi, Dae Eun; Jeong, Jin Young; Lim, Beom Jin; Lee, Kang Wook; Shin, Young-Tai; Na, Ki-Ryang

    2009-01-01

    Background/Aims Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. Methods Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hour...

  20. Ameliorative effect of selenium in cisplatin-induced testicular damage in rats.

    Science.gov (United States)

    Simsek, Nejdet; Koc, Akif; Karadeniz, Ali; Yildirim, Mehmet Erol; Celik, Hüseyin Tuğrul; Sari, Erhan; Kara, Adem

    2016-04-01

    In this study, we investigated the protective effect of selenium (Se) on cisplatin (Cis) induced testicular damage using histopathological, immunohistochemical and biochemical approaches. Twenty-one male Wistar rats were equally divided into three groups of seven rats each: control (C), Cis, and Cis+Se. Cis and Cis+Se group rats received Cis at a dose of 12mg/kg b.w./day, intraperitoneally for 3 consecutive days. Cis+Se group rats received selenium via oral gavage 3mg/kg/day (twice-a day as 1.5mg/kg) until 11th consecutive days starting at 5 days before cisplatin injection. C group received only 0.9% NaCl intraperitoneally and orally at same time and at equal volume. After the treatment, the histopathological, immunohistochemical and biochemical examinations were performed. In seminiferous tubules of Cis treated rats were observed the most consistent findings characterized with vacuolization, desquamation, disorganization, and also was a considerable reduction in elongated spermatids, however the Cis+Se group exhibited improved histopathologic changes. In the immunohistochemical examinations, caspase-3 immunopositive cells displayed higher in the Cis group according to C and Cis+Se groups. Bcl-2 and NF-κB staining revealed a moderate number in the C group and significantly fewer in the Cis group compared to the Cis+Se groups. Additionally, MDA levels were also significantly increased in the Cis group in comparison to Control group, but pretreatment with selenium prevented elevation of MDA levels significantly in Cis+Se group rats. This study indicates that Cis-treatment induced testicular apoptosis and lipid peroxidation, and combined treatment with selenium prevented severity of the toxicity in rats. PMID:26920108

  1. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

    OpenAIRE

    Uribe, Phillip M.; Mueller, Melissa A.; Gleichman, Julia S.; Kramer, Matthew D.; Qi Wang; Martha Sibrian-Vazquez; Strongin, Robert M.; Peter S Steyger; Douglas A Cotanche; Matsui, Jonathan I.

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under ...

  2. Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats

    OpenAIRE

    S. Noori; Mahboob, Tabassum

    2010-01-01

    Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Carnosine is a naturally occurring dipeptide and has a scavenging property. The aim of present study was to assess the lipid peroxidation and antioxidant enzymes in association with oxidative stress in cisplatin -treated and 10 subsequent doses of carnosine-pretreated rats. 24 male Albino Wistar rats, were randomly divided into four groups (n=6). Group I remains untreated; Group II received Cisplatin (3 mg ...

  3. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    Energy Technology Data Exchange (ETDEWEB)

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Shahverdi, Ahmad Reza [Department of Pharmaceutical Biotechnology and Biotechnology Research Centre, Faculty of Pharmacy, TUMS, Tehran (Iran, Islamic Republic of); Ahmadi, Abbas [Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia (Iran, Islamic Republic of); Baeeri, Maryam; Mohammadirad, Azadeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ► Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ► Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ► CIS-exposure induces oxidative sperm DNA damage and impairs steroidogenesis. ► Nano-Se retained sperm quality against CIS-induced free radicals toxic stress.

  4. δ-阿片受体抑制阿片诱发痛觉过敏的研究进展%The role of δ- opioid receptor in the inhibition of opioid induced hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    李依泽; 王海云; 王国林

    2012-01-01

    Background Opioids are the most powerful analgesics for the treatment of moderate to severe pain.Although opioids have analgesic effect,they have many side effects at the same time.Long term opioids exposure can induce hyperalgesia and tolerance.Moreover,increasing the dose of opioids,paradoxically,aggravates the hyperalgesia and tolerance,causing a vicious cycle.The use of opioids,therefore,is largely limited in the clinical setting. Objective The relevant literatures involved in the role of δ-opioid receptors in the attenuation of opioid induced hyperalgesia (OIH) in recent years were summarized,which helps readership to update the latest information about this topic. Content The structure,distribution,physiological function and the progress of antihyperalgesic effect of δ-opioid receptors were reviewed in this article.Those researches suggest that OIH and tolerance can be attenuated by the inhibition of δ-opioid receptor phosphorylation,knocking out δ-opioid receptor coding genes and the application of δ-opioid receptor antagonists. Trend Since the antihyperalgesia effect of δ-opioid receptor is widely acknowledged,δ- opioid receptor may become a new target to relieve pain in the clinical setting.%背景 阿片类药物是治疗中、重度疼痛的主要药物,长时间应用可出现阿片诱发的痛觉过敏和耐受,而增加药物剂量可造成更严重的痛觉过敏和耐受,从而形成恶性循环,很大程度上限制了阿片类药物在临床工作中的应用.目的 通过对近年δ-阿片受体在痛觉过敏中所起作用的研究进行总结,帮助读者了解国外相关研究的最新趋势和进展.内容 就δ-阿片受体的结构、分布、生理功能和δ-阿片受体的抗痛觉过敏作用的研究进展进行综述.得出如下结论,通过抑制δ-阿片受体磷酸化、敲除δ-阿片受体编码基因和应用δ-阿片受体拮抗剂等方法,可抑制痛觉过敏和耐受的形成.趋向 随着越来越多的学者对

  5. Heat Rash or Prickly Heat (Miliaria Rubra)

    Science.gov (United States)

    ... rash and rashes clinical tools newsletter | contact Share | Heat Rash or Prickly Heat (Miliaria Rubra) Information for adults A A A ... bumps can suddenly occur, as seen here. Overview Heat rash (miliaria rubra), also known as prickly heat, ...

  6. Post heat shock tolerance: a neuroimmunological anti-inflammatory phenomenon

    Directory of Open Access Journals (Sweden)

    Jazani Nima

    2009-03-01

    Full Text Available Abstract We previously showed that the progression of burn-induced injury was inhibited by exposing the peripheral area of injured skin to sublethal hyperthermia following the burn. We called this phenomenon post-heat shock tolerance. Here we suggest a mechanism for this phenomenon. Exposure of the peripheral primary hyperalgesic/allodynic area of burned skin to local hyperthermia (45°C, 30 seconds, which is a non-painful stimulus for normal skin, results in a painful sensation transmitted by nociceptors. This hyperthermia is too mild to induce any tissue injury, but it does result in pain due to burn-induced hyperalgesia/allodynia. This mild painful stimulus can result in the induction of descending anti-nociceptive mechanisms, especially in the adjacent burned area. Some of these inhibitory mechanisms, such as alterations of sympathetic outflow and the production of endogenous opioids, can modify peripheral tissue inflammation. This decrease in burn-induced inflammation can diminish the progression of burn injury.

  7. Heat exchanger

    International Nuclear Information System (INIS)

    A heat exchanger having primary and secondary conduits in heat-exchanging relationship is described comprising: at least one serpentine tube having parallel sections connected by reverse bends, the serpentine tube constituting one of the conduits; a group of open-ended tubes disposed adjacent to the parallel sections, the open-ended tubes constituting the other of the conduits, and forming a continuous mass of contacting tubes extending between and surrounding the serpentine tube sections; and means securing the mass of tubes together to form a predetermined cross-section of the entirety of the mass of open-ended tubes and tube sections

  8. Monopole heat

    International Nuclear Information System (INIS)

    Upper bounds on the flux of monopoles incident on the Earth with velocity -5 c(1016 GeV m-1) and on the flux of monopoles incident on Jupiter with velocity -3 c(1016 GeV m-1), are derived. Monopoles moving this slowly lose sufficient energy to be stopped, and then catalyse nucleon decay, releasing heat. The limits are obtained by requiring the rate of energy release from nucleon decay to be less than the measured amount of heat flowing out from the surface of the planet. (U.K.)

  9. Heat transfer

    CERN Document Server

    Holman, J P

    2010-01-01

    As one of the most popular heat transfer texts, Jack Holman's "Heat Transfer" is noted for its clarity, accessible approach, and inclusion of many examples and problem sets. The new tenth edition retains the straight-forward, to-the-point writing style while covering both analytical and empirical approaches to the subject. Throughout the book, emphasis is placed on physical understanding while, at the same time, relying on meaningful experimental data in those situations that do not permit a simple analytical solution. New examples and templates provide students with updated resources for computer-numerical solutions.

  10. Heat exchanger

    International Nuclear Information System (INIS)

    A heat exchanger of the straight tube type is described in which different rates of thermal expansion between the straight tubes and the supply pipes furnishing fluid to those tubes do not result in tube failures. The supply pipes each contain a section which is of helical configuration

  11. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... for signs of heat stroke or exhaustion. Heat Stroke and Exhaustion Symptoms of early heat exhaustion symptoms ... heavy sweating; nausea; and giddiness. Symptoms of heat stroke (late stage of heat illness) include flushed, hot, ...

  12. Heat Exchanger

    International Nuclear Information System (INIS)

    A liquid metal heated tube and shell heat exchanger where straight tubes extend between upper and lower tube sheets. In order to prevent thermal stress problems, one tube sheet is fixed to the shell, and the other tube sheet is sealed to the shell by means of a flexible bellows. In the event of a catastrophic bellows failure, a housing that utilizes a packing gland sliding seal is used to enclose and back-up the bellows. Also, a key and slot arrangement is provided for preventing relative rotation between the shell and tube sheet which could damage the bellows and cause failure thereof. This exchanger is seen to be of use in sodium cooled reactors between the liquid sodium circuit on the steam generator

  13. 'Heat Dome' Heats Up United States

    Science.gov (United States)

    ... news/fullstory_160028.html 'Heat Dome' Heats Up United States Much of the country to be under ... As a massive "heat dome" stretches across the United States this week, sending temperatures and humidity levels ...

  14. Heating systems for heating subsurface formations

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Scott Vinh (Houston, TX); Vinegar, Harold J. (Bellaire, TX)

    2011-04-26

    Methods and systems for heating a subsurface formation are described herein. A heating system for a subsurface formation includes a sealed conduit positioned in an opening in the formation and a heat source. The sealed conduit includes a heat transfer fluid. The heat source provides heat to a portion of the sealed conduit to change phase of the heat transfer fluid from a liquid to a vapor. The vapor in the sealed conduit rises in the sealed conduit, condenses to transfer heat to the formation and returns to the conduit portion as a liquid.

  15. Heat transfer

    CERN Document Server

    Jorge, Kubie; Thomas, Grassie

    2012-01-01

    A core task of engineers is to analyse energy related problems. The analytical treatment is usually based on principles of thermodynamics, fluid mechanics and heat transfer, but is increasingly being handled computationally.This unique resource presents a practical textbook, written for both undergraduates and professionals, with a series of over 60 computer workbooks on an accompanying CD.The book emphasizes how complex problems can be deconstructed into a series of simple steps. All thermophysical property computations are illustrated using diagrams within text and on the compani

  16. Heat pipes

    CERN Document Server

    Dunn, Peter D

    1982-01-01

    A comprehensive, up-to-date coverage of the theory, design and manufacture of heat pipes and their applications. This latest edition has been thoroughly revised, up-dated and expanded to give an in-depth coverage of the new developments in the field. Significant new material has been added to all the chapters and the applications section has been totally rewritten to ensure that topical and important applications are appropriately emphasised. The bibliography has been considerably enlarged to incorporate much valuable new information. Thus readers of the previous edition, which has established

  17. Radiofrequency plasma heating: proceedings

    International Nuclear Information System (INIS)

    The conference proceedings include sessions on Alfven Wave Heating, ICRF Heating and Current Drive, Lower Hybrid Heating and Current Drive, and ECRF Heating. Questions of confinement, diagnostics, instabilities and technology are considered. Individual papers are cataloged separately

  18. Heat-Related Illnesses

    Science.gov (United States)

    ... Emergencies A-Z Share this! Home » Emergency 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at ... about heat cramps and heat stroke and exhaustion. Heat Cramps Symptoms include muscle spasms, usually in the ...

  19. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... Emergencies A-Z Share this! Home » Emergency 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at ... about heat cramps and heat stroke and exhaustion. Heat Cramps Symptoms include muscle spasms, usually in the ...

  20. Low temperature nuclear heat

    Energy Technology Data Exchange (ETDEWEB)

    Kotakorpi, J.; Tarjanne, R. (comps.)

    1977-08-01

    The meeting was concerned with the use of low grade nuclear heat for district heating, desalination, process heat, and agriculture and aquaculture. The sessions covered applications and demand, heat sources, and economics.

  1. Segmented heat exchanger

    Science.gov (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann

    2010-12-14

    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  2. Heat pumps in district heating networks

    DEFF Research Database (Denmark)

    Ommen, Torben Schmidt; Markussen, Wiebke Brix; Elmegaard, Brian

    In the current Danish energy system, the majority of electricity and heat is produced in combined heat and power plants. With increasing shares of intermittent renewable power production, it becomes a challenging task to match power and heat production, as heat demand and production capacity...... constraints limit the power plants. Efficient heat pumps can be used to decouple the constraints of electricity and heat production, while maintaining the high energy efficiency needed to match the politically agreed carbon emission goals. The requirements in terms of COP, location, capacity and economy...... and strategic planning in the energy sector. The paper presents a case study of optimal implementation of heat pumps in the present energy system of the Copenhagen area. By introduction of the correct capacity of heat pumps, a 1,6 % reduction in fuel consumption for electricity and heat production can...

  3. Heat pump technology

    CERN Document Server

    Von Cube, Hans Ludwig; Goodall, E G A

    2013-01-01

    Heat Pump Technology discusses the history, underlying concepts, usage, and advancements in the use of heat pumps. The book covers topics such as the applications and types of heat pumps; thermodynamic principles involved in heat pumps such as internal energy, enthalpy, and exergy; and natural heat sources and energy storage. Also discussed are topics such as the importance of the heat pump in the energy industry; heat pump designs and systems; the development of heat pumps over time; and examples of practical everyday uses of heat pumps. The text is recommended for those who would like to kno

  4. Cryogenic heat transfer

    CERN Document Server

    Barron, Randall F

    2016-01-01

    Cryogenic Heat Transfer, Second Edition continues to address specific heat transfer problems that occur in the cryogenic temperature range where there are distinct differences from conventional heat transfer problems. This updated version examines the use of computer-aided design in cryogenic engineering and emphasizes commonly used computer programs to address modern cryogenic heat transfer problems. It introduces additional topics in cryogenic heat transfer that include latent heat expressions; lumped-capacity transient heat transfer; thermal stresses; Laplace transform solutions; oscillating flow heat transfer, and computer-aided heat exchanger design. It also includes new examples and homework problems throughout the book, and provides ample references for further study.

  5. Heat Rash or Prickly Heat (Miliaria Rubra)

    Science.gov (United States)

    ... heat rash consist of controlling heat and humidity. Acetaminophen or ibuprofen can help to reduce fever. Remove ... without any sweat. Your child may complain of dizziness, nausea, weakness, headache, confusion, or difficulty breathing. This ...

  6. Multidimensional Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten

    1998-01-01

    Analytical theory of multidimensional heat conduction. General heat conduction equation in three dimensions. Steay state, analytical solutions. The Laplace equation. Method of separation of variables. Principle of superposition. Shape factors. Transient, multidimensional heat conduction....

  7. Oscillating heat pipes

    CERN Document Server

    Ma, Hongbin

    2015-01-01

    This book presents the fundamental fluid flow and heat transfer principles occurring in oscillating heat pipes and also provides updated developments and recent innovations in research and applications of heat pipes. Starting with fundamental presentation of heat pipes, the focus is on oscillating motions and its heat transfer enhancement in a two-phase heat transfer system. The book covers thermodynamic analysis, interfacial phenomenon, thin film evaporation,  theoretical models of oscillating motion and heat transfer of single phase and two-phase flows, primary  factors affecting oscillating motions and heat transfer,  neutron imaging study of oscillating motions in an oscillating heat pipes, and nanofluid’s effect on the heat transfer performance in oscillating heat pipes.  The importance of thermally-excited oscillating motion combined with phase change heat transfer to a wide variety of applications is emphasized. This book is an essential resource and learning tool for senior undergraduate, gradua...

  8. Heat Cramps, First Aid

    Science.gov (United States)

    ... rashes clinical tools newsletter | contact Share | Heat Cramps, First Aid A A A Heat cramp signs and symptoms ... if later stages of heat illness are suspected. First Aid Guide Use a combination of the following measures, ...

  9. Heat Exhaustion, First Aid

    Science.gov (United States)

    ... rashes clinical tools newsletter | contact Share | Heat Exhaustion, First Aid A A A Heat exhaustion signs and symptoms ... specific to the other stages of heat illness. First Aid Guide Use a combination of the following measures ...

  10. Solar heat storages in district heating networks

    Energy Technology Data Exchange (ETDEWEB)

    Ellehauge, K. (Ellehauge og Kildemoes, AArhus (DK)); Engberg Pedersen, T. (COWI A/S, Kgs. Lyngby (DK))

    2007-07-15

    This report gives information on the work carried out and the results obtained in Denmark on storages for large solar heating plants in district heating networks. Especially in Denmark the share of district heating has increased to a large percentage. In 1981 around 33% of all dwellings in DK were connected to a district heating network, while the percentage in 2006 was about 60% (in total 1.5 mio. dwellings). In the report storage types for short term storage and long term storages are described. Short term storages are done as steel tanks and is well established technology widely used in district heating networks. Long term storages are experimental and used in connection with solar heating. A number of solar heating plants have been established with either short term or long term storages showing economy competitive with normal energy sources. Since, in the majority of the Danish district heating networks the heat is produced in co-generation plants, i.e. plants producing both electricity and heat for the network, special attention has been put on the use of solar energy in combination with co-generation. Part of this report describes that in the liberalized electricity market central solar heating plants can also be advantageous in combination with co-generation plants. (au)

  11. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    Hansen, Kenneth; Connolly, David; Lund, Henrik;

    2015-01-01

    The cost of heat savings in buildings increase as more heat savings are achieved due to the state of the building stock and hence, alternatives other than savings typically become more economically feasible at a certain level of heat reductions. It is important to identify when the cost of heat s...

  12. Transient Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten

    1998-01-01

    Analytical theory of transient heat conduction.Fourier's law. General heat conducation equation. Thermal diffusivity. Biot and Fourier numbers. Lumped analysis and time constant. Semi-infinite body: fixed surface temperature, convective heat transfer at the surface, or constant surface heat flux...

  13. The Gravitational Heat Exchanger

    OpenAIRE

    De Aquino, Fran

    2015-01-01

    The heat exchangers are present in many sectors of the economy. They are widely used in Refrigerators, Air-conditioners, Engines, Refineries, etc. Here we show a heat exchanger that works based on the gravity control. This type of heat exchanger can be much more economic than the conventional heat exchangers.

  14. Nature's Heat Exchangers.

    Science.gov (United States)

    Barnes, George

    1991-01-01

    Discusses the heat-transfer systems of different animals. Systems include heat conduction into the ground, heat transferred by convection, heat exchange in lizards, fish and polar animals, the carotid rete system, electromagnetic radiation from animals and people, and plant and animal fiber optics. (MDH)

  15. Heat Pipe Planets

    Science.gov (United States)

    Moore, William B.; Simon, Justin I.; Webb, A. Alexander G.

    2014-01-01

    When volcanism dominates heat transport, a terrestrial body enters a heat-pipe mode, in which hot magma moves through the lithosphere in narrow channels. Even at high heat flow, a heat-pipe planet develops a thick, cold, downwards-advecting lithosphere dominated by (ultra-)mafic flows and contractional deformation at the surface. Heat-pipes are an important feature of terrestrial planets at high heat flow, as illustrated by Io. Evidence for their operation early in Earth's history suggests that all terrestrial bodies should experience an episode of heat-pipe cooling early in their histories.

  16. The Heat Is On

    OpenAIRE

    Brian Hill

    2014-01-01

    Qualification in track and field events involves runners competing against individuals within their heat and runners in other heats. Given that the heats are run sequentially, runners in each heat have different information about their competitors. Using data on track and field events from 2001-2011, this article examines whether an individual’s placement in a specific heat and their peers affect their performance and qualification probability. Results indicate that runners’ times and qua...

  17. [Heat waves: health impacts].

    Science.gov (United States)

    Marto, Natália

    2005-01-01

    During the summer of 2003, record high temperatures were reported across Europe, causing thousands of casualties. Heat waves are sporadic recurrent events, characterised by intense and prolonged heat, associated with excess mortality and morbidity. The most frequent cause of death directly attributable to heat is heat stroke but heat waves are known to cause increases in all-cause mortality, specially circulatory and respiratory mortality. Epidemiological studies demonstrate excess casualties cluster in specific risk groups. The elderly, those with chronic medical conditions and the socially isolated are particularly vulnerable. Air conditioning is the strongest protective factor against heat-related disorders. Heat waves cause disease indirectly, by aggravating chronic disorders, and directly, by causing heat-related illnesses (HRI). Classic HRI include skin eruptions, heat cramps, heat syncope, heat exhaustion and heat stroke. Heat stroke is a medical emergency characterised by hyperthermia and central nervous system dysfunction. Treatment includes immediate cooling and support of organ-system function. Despite aggressive treatment, heat stroke is often fatal and permanent neurological damage is frequent in those who survive. Heat related illness and death are preventable through behavioural adaptations, such as use of air conditioning and increased fluid intake. Other adaptation measures include heat emergency warning systems and intervention plans and environmental heat stress reduction. Heat related mortality is expected to rise as a consequence of the increasing proportion of elderly persons, the growing urban population, and the anticipated increase in number and intensity of heat waves associated with global warming. Improvements in surveillance and response capability may limit the adverse health conditions of future heat waves. It is crucial that health professionals are prepared to recognise, prevent and treat HRI and learn to cooperate with local health

  18. Introduction to heat transfer

    CERN Document Server

    SUNDÉN, B

    2012-01-01

    Presenting the basic mechanisms for transfer of heat, Introduction to Heat Transfer gives a deeper and more comprehensive view than existing titles on the subject. Derivation and presentation of analytical and empirical methods are provided for calculation of heat transfer rates and temperature fields as well as pressure drop. The book covers thermal conduction, forced and natural laminar and turbulent convective heat transfer, thermal radiation including participating media, condensation, evaporation and heat exchangers.

  19. Open district heating and marginal cost based heat pricing

    OpenAIRE

    Mäkelä, Henri

    2014-01-01

    Currently, an increasing usage of individual heating systems such as heat pumps and solar heat collectors, pose a challenge to the district heating market. However, individual heating technologies together with industrial processes produce excess heat, which can be utilized in district heating. The usage of excess heat can be seen as an opportuni-ty for new business strategies in district heating. The objective of this thesis was to simulate hourly district heat production in an open dist...

  20. Basic heat transfer

    CERN Document Server

    Bacon, D H

    2013-01-01

    Basic Heat Transfer aims to help readers use a computer to solve heat transfer problems and to promote greater understanding by changing data values and observing the effects, which are necessary in design and optimization calculations.The book is concerned with applications including insulation and heating in buildings and pipes, temperature distributions in solids for steady state and transient conditions, the determination of surface heat transfer coefficients for convection in various situations, radiation heat transfer in grey body problems, the use of finned surfaces, and simple heat exc

  1. Microscale Regenerative Heat Exchanger

    Science.gov (United States)

    Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

    2006-01-01

    The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

  2. Plasma heat pump and heat engine

    International Nuclear Information System (INIS)

    A model system where cold charged particles are locally confined in a volume VP within a warm plasma of volume V (VPE. The law of thermodynamics involving PE and an equation of state for PE are obtained. It is shown that the expansion/compression of electrostatic fields associated with charged particles is a new mechanism that converts mechanical work into plasma heat and vice versa. Two applications of this theory are, first we propose a pumping device which heats plasmas by an adiabatic/isothermal compression of fields. Heating power ranging from a few hundred watts to a few kilowatts is possible with the present day technology. Second, we discuss the feasibility of constructing an electrostatic heat engine which converts plasma heat into mechanical work via plasma electric fields. Effects of PE are shown to be observable in colloidal solutions.

  3. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... 911 What To Do In A Medical Emergency Childhood Emergencies Careers in Emergency Medicine Seconds Save Lives ... or exhaustion. Heat Stroke and Exhaustion Symptoms of early heat exhaustion symptoms include cool, moist, pale or ...

  4. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... for Disasters Communication With Your Family And Your Doctor About Your Wishes Visiting the ER Who Takes ... 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at Mercy Health System in Chesterfield, Missouri Heat- ...

  5. Heat Wave Safety Checklist

    Science.gov (United States)

    ... itself. ❏ Signs of heat stroke include hot, red skin which may be dry or moist; changes in consciousness; vomiting; and high body temperature. ❏ Heat stroke is life-threatening. Call 9-1-1 or ...

  6. Salix to heat glasshouses

    Energy Technology Data Exchange (ETDEWEB)

    Tremeer, R.

    1993-12-31

    A wood chip heating plant supplied by short rotation coppice and existing woodland and hedges is used to heat glass houses. The reasons for changing to wood-fuel are developed in the paper. (TEC). 1 fig.

  7. Convective heat transfer

    CERN Document Server

    Kakac, Sadik; Pramuanjaroenkij, Anchasa

    2014-01-01

    Intended for readers who have taken a basic heat transfer course and have a basic knowledge of thermodynamics, heat transfer, fluid mechanics, and differential equations, Convective Heat Transfer, Third Edition provides an overview of phenomenological convective heat transfer. This book combines applications of engineering with the basic concepts of convection. It offers a clear and balanced presentation of essential topics using both traditional and numerical methods. The text addresses emerging science and technology matters, and highlights biomedical applications and energy technologies. What’s New in the Third Edition: Includes updated chapters and two new chapters on heat transfer in microchannels and heat transfer with nanofluids Expands problem sets and introduces new correlations and solved examples Provides more coverage of numerical/computer methods The third edition details the new research areas of heat transfer in microchannels and the enhancement of convective heat transfer with nanofluids....

  8. Radial heat flux transformer

    Science.gov (United States)

    Basiulis, A.; Buzzard, R. J.

    1971-01-01

    Unit moves heat radially from small diameter shell to larger diameter shell, or vice versa, with negligible temperature drop, making device useful wherever heating or cooling of concentrically arranged materials, substances, and structures is desired.

  9. Regenerative heat sources for heating networks

    International Nuclear Information System (INIS)

    The ambitious goal, the German Federal Government has set itself, to reduce the emissions of greenhouse gases by 80% to 95% by the year 2050. As there are currently more than half of German energy consumption for the production of heat is required, big contributions to climate protection can be expected from this area if more renewable heat sources are used. Renewable heat sources such as bioenergy, solar thermal and geothermal energy in particular can be provided as compared to fossil fuels with significantly lower specific CO2 emissions. Objectives in the heating market and scenarios for the transformation of the heat sector have been elaborated in the BMU Lead Study 2011. The main pillar of this scenario is the reduction of final energy consumption for heat by the energy-efficient renovation of existing buildings and further increasing demands on the energetic quality of new buildings. To cover the remaining energy demand, a focus is on the expansion of heating networks based on renewable energies.

  10. Action of (R)-sila-venlafaxine and reboxetine to antagonize cisplatin-induced acute and delayed emesis in the ferret

    International Nuclear Information System (INIS)

    The chemotherapeutic drug cisplatin is associated with severe gastrointestinal toxicity that can last for several days. A recent strategy to treat the nausea and emesis includes the combination of a 5-HT3 receptor antagonist, a glucocorticoid, and an NK1 receptor antagonist. The present studies explore the use of the selective noradrenaline reuptake inhibitors, (R)-sila-venlafaxine, (R,R)-reboxetine and (S,S)-reboxetine to prevent cisplatin (5 mg/kg, i.p.)-induced acute (0-24 h) and delayed (24-72 h) emesis in ferrets. The positive control regimen of ondansetron and dexamethasone, both at 1 mg/kg/8 h, reduced acute and delayed emesis by 100 (P 0.05). In conclusion, the studies provide the first evidence for an anti-emetic potential of noradrenaline reuptake inhibitors to reduce chemotherapy-induced acute and delayed emesis

  11. Protective effect of hydroalcoholic extract of tribulus terrestris on cisplatin induced renal tissue damage in male mice

    OpenAIRE

    Amir Raoofi; Mozafar Khazaei; Ali Ghanbari

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg ...

  12. Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

    OpenAIRE

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extr...

  13. Protective effect of hydroalcoholic extract of tribulus terrestris on cisplatin induced renal tissue damage in male mice

    Directory of Open Access Journals (Sweden)

    Amir Raoofi

    2015-01-01

    Full Text Available Background: According beneficial effects of Tribulus terrestris (TT extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS (EBEWE Pharma, Unterach, Austria induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6. The first group (control was treated with normal saline (0.9% NaCl and experimental groups with CIS (E1, CIS + 100 mg/kg extract of TT (E2, CIS + 300 mg/kg extract of TT (E3, CIS + 500 mg/kg extract of TT (E4 intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey′s post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman′s capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  14. Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy

    Directory of Open Access Journals (Sweden)

    Egensperger Rupert

    2009-07-01

    Full Text Available Abstract Background Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG cells leading to sensory polyneuropathy (PNP. We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden. Results A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s ± 1,68 m/s; cisplatin + rhEPO 49,66 m/s ± 1,26 m/s; control 55,01 m/s ± 1,88 m/s; p Conclusion The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.

  15. Reduction of cisplatin-induced nephrotoxicity in vivo by selenomethionine: the effect on cisplatin-DNA adducts.

    Science.gov (United States)

    García Sar, Daniel; Montes-Bayón, Maria; Blanco González, Elisa; Sierra Zapico, Luisa M; Sanz-Medel, Alfredo

    2011-06-20

    Cisplatin is one of the most effective chemotherapeutic agents, although its clinical use is limited by severe renal toxicity. This toxicity seems to be related to the accumulation of the drug in kidney tissues, leading to renal failure. For this reason, several compounds have been evaluated to ameliorate the nephrotoxicity induced by cisplatin. In the present investigation, we report the effect of the oral administration of selenomethionine before intraperitoneal cisplatin treatment. The preadministration of this Se species has been shown to have an important effect in reducing renal damage induced by cisplatin by increasing the excreted urea and improving creatinine clearance. Quantification of the level of DNA--cisplatin adducts in kidney and liver tissues was carried out by postcolumn isotope dilution analysis using liquid chromatography-inductively coupled plasma (LC-ICP-MS) as speciation set up. The level of DNA--cisplatin adducts in rats given Se-methionine in the drinking water before cisplatin administration was considerably lower in kidney tissues with respect to the animals drinking only water. Such effects were not observed in liver tissue. Initial speciation studies of Pt and Se conducted in kidney tissues of exposed animals by HPLC-ICP-MS have revealed the presence of cisplatin as part of a complex with Se-methionine, which can be eventually excreted into urine. This Pt--Se complex could explain the observed reduction of the kidney damage in Se-methionine-treated animals. PMID:21491944

  16. Cisplatin-Induced DNA Damage Activates Replication Checkpoint Signaling Components that Differentially Affect Tumor Cell SurvivalS⃞

    OpenAIRE

    Wagner, Jill M.; Karnitz, Larry M.

    2009-01-01

    Cisplatin and other platinating agents are some of the most widely used chemotherapy agents. These drugs exert their antiproliferative effects by creating intrastrand and interstrand DNA cross-links, which block DNA replication. The cross-links mobilize signaling and repair pathways, including the Rad9-Hus1-Rad1-ATR-Chk1 pathway, a pathway that helps tumor cells survive the DNA damage inflicted by many chemotherapy agents. Here we show that Rad9 and ATR play critical r...

  17. Mutations in cockayne syndrome-associated genes (Csa and Csb) predispose to cisplatin-induced hearing loss in mice

    NARCIS (Netherlands)

    R.N. Rainey (Robert N.); S.-Y. Ng (Sum-Yan); J. Llamas (Juan); G.T.J. van der Horst (Gijsbertus); N. Segil (Neil)

    2016-01-01

    textabstractCisplatin is a common and effective chemotherapeutic agent, yet it often causes permanent hearing loss as a result of sensory hair cell death. The causes of sensitivity to DNA-damaging agents in nondividing cell populations, such as cochlear hair and supporting cells, are poorly understo

  18. The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect

    Directory of Open Access Journals (Sweden)

    Farzaneh Ashrafi

    2012-01-01

    Results: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated was significantly higher compared with the positive control group (Group 4, P < 0.05. The increase in blood urea nitrogen (BUN and creatinine (Cr levels in serum in Group 1 were more than those in other groups ( P < 0.05. No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05. Conclusion: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

  19. An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced acute and delayed emesis in the ferret.

    OpenAIRE

    Rudd, J. A.; Naylor, R. J.

    1996-01-01

    1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of ondansetron and dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg kg-1, i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60-76 and 73-84%. On the third da...

  20. Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells.

    Science.gov (United States)

    Velma, Venkatramreddy; Dasari, Shaloam R; Tchounwou, Paul B

    2016-01-01

    Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 µM using HL-60 cells as a test model. We investigated cisplatin effects at the molecular level using RNA sequencing, cell cycle analysis, and apoptotic assay after 24, 48, 72, and 96 hours of treatment. The results show that many genes responsible for molecular and cellular functions were significantly altered. Cisplatin treatment also caused the cells to be arrested at the DNA synthesis phase, and as the time increases, the cells gradually accumulated at the sub-G1 phase. Also, as the dose increases, a significant number of cells entered into the apoptotic and necrotic stages. Altogether, the data show that low doses of cisplatin significantly impact the viability of HL-60 cells, through modulation of gene expression, cell cycle, and apoptosis. PMID:27594783

  1. Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Guan-gui Chen

    2015-01-01

    Full Text Available Polyethyleneimine-polyethylene glycol (PEI-PEG, a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

  2. Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets

    OpenAIRE

    Santiago, Maria José; Fernández, Sarah Nicole; Lázaro, Alberto; González, Rafael; Urbano, Javier; López, Jorge; Solana, Maria José; Toledo, Blanca; del Castillo, Jimena; Tejedor, Alberto; López-Herce, Jesús

    2016-01-01

    Objective To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. Methods Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared betw...

  3. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  4. Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats

    OpenAIRE

    Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Ashrafi, Farzaneh

    2013-01-01

    Background Cisplatin (CP) therapy as the most common potent chemotherapeutic process is accompanied by nephrotoxicity. The diabetic state may protect rat kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the glucose level in diabetic animals. Objectives Current study was planned to investigate the effect of oral administration of magnesium supplementation on CP-induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats. Materials and Methods Male...

  5. Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK

    OpenAIRE

    Pereira, Lorena; Igea, Ana; Canovas, Begoña; Dolado, Ignacio; Nebreda, Angel R

    2013-01-01

    The p38 MAPK pathway is an important regulator of many cellular responses. It is well established that p38 MAPK signalling negatively regulates epithelial cell transformation, but enhanced p38 MAPK activity has been also correlated with bad clinical prognosis in some tumour types. Here, we provide genetic and pharmacological evidence showing that p38 MAPK inhibition cooperates with the chemotherapeutic agent cisplatin to kill tumour cells. We show that p38 MAPK inhibition results in ROS upreg...

  6. Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Lisá, Věra; Malík, Radek; Kozáková, Hana; Šedo, A.

    2003-01-01

    Roč. 18, č. 3 (2003), s. 687-693. ISSN 0213-3911 R&D Projects: GA ČR GA301/02/0962 Institutional research plan: CEZ:AV0Z5020903; CEZ:AV0Z5011922 Keywords : glioma * cisplatin * gamma-glutamytranspeptidase Subject RIV: FD - Oncology ; Hematology Impact factor: 1.830, year: 2003

  7. Heat exchanger design

    OpenAIRE

    Loukota, Martin

    2014-01-01

    This bachelor thesis solves design of a heat exchanger for hot water boiler with gasification chamber for preheating the combustion air with the heat of the combustion products. Calculation values were experimentally measured. Thesis contains brief description of the shell and tube heat exchanger, stoichiometric combustion calculation, geometrical dimensions design of the heat exchanger, pressure loss and thermal performance calculation. It also includes drawings of the designed exchanger.

  8. Estimation of Heating Device‘s Convective Heat Transfer of Heat Supply Systems with Rotational Heat Generator

    Directory of Open Access Journals (Sweden)

    A. Nesenchuk

    2014-09-01

    Full Text Available In this article, on the base of heat exchange analysis in heat supply systems with rotational heat generator, a calculated formula for estimation of heat transfer from the surface of heating device is obtained, taking into account its probability (random orientation in space. It is shown the most probable position of heating devices in heating system of mobile object.

  9. Estimation of Heating Device‘s Convective Heat Transfer of Heat Supply Systems with Rotational Heat Generator

    OpenAIRE

    A. Nesenchuk; I. Iokova; T. Rizova; P. Lasij; D. Shklovchik; Z. Aidarova

    2014-01-01

    In this article, on the base of heat exchange analysis in heat supply systems with rotational heat generator, a calculated formula for estimation of heat transfer from the surface of heating device is obtained, taking into account its probability (random) orientation in space. It is shown the most probable position of heating devices in heating system of mobile object.

  10. Liquid heat capacity lasers

    Science.gov (United States)

    Comaskey, Brian J.; Scheibner, Karl F.; Ault, Earl R.

    2007-05-01

    The heat capacity laser concept is extended to systems in which the heat capacity lasing media is a liquid. The laser active liquid is circulated from a reservoir (where the bulk of the media and hence waste heat resides) through a channel so configured for both optical pumping of the media for gain and for light amplification from the resulting gain.

  11. Heat roadmap China

    DEFF Research Database (Denmark)

    Xiong, Weiming; Wang, Yu; Mathiesen, Brian Vad;

    2015-01-01

    District heating is regarded as a key element of energy saving actions in the Chinese national energy strategy, while space heating in China is currently still dominated by coal boilers. However, there is no existing quantitative study to analyse the future heat strategy for China. Therefore, it ...

  12. Urban heat island

    Science.gov (United States)

    Kim, Hongsuk H.

    1991-01-01

    The phenomenon of urban heat island was investigated by the use of LANDSAT Thematic Mapper data sets collected over the metropolitan area of Washington DC (U.S.). By combining the retrieved spectral albedos and temperatures, urban modification on radiation budgets of five surface categories were analyzed. The surface radiation budget imagery of the area show that urban heating is attributable to a large heat flux from the rapidly heating surfaces of asphalt, bare soil and short grass. In summer, symptoms of diurnal heating begin to appear by mid morning and can be about 10 degrees warmer than nearby woodlands in summer.

  13. Ground Source Heat Pumps

    OpenAIRE

    Lale Valizade

    2013-01-01

    A heat pump is a device that is able to transfer heat from one fluid at a lower temperature to another at a higher temperature. Ground source heat pumps are generally classified by the type of ground loop. The coefficient of performance (COP) is used to define the heating performance of heat pumps. Both the COP and EER values are valid only at the specific test conditions used in the rating. A ground source pump could reach 450%, compared with an efficient gas boiler of 90% obviously this is ...

  14. Single Electrode Heat Effects

    DEFF Research Database (Denmark)

    Jacobsen, Torben; Broers, G. H. J.

    1977-01-01

    The heat evolution at a single irreversibly working electrode is treated onthe basis of the Brønsted heat principle. The resulting equation is analogous to the expression for the total heat evolution in a galvanic cellwith the exception that –DeltaS is substituted by the Peltier entropy, Delta......SP, of theelectrode reaction. eta is the overvoltage at the electrode. This equation is appliedto a high temperature carbonate fuel cell. It is shown that the Peltier entropyterm by far exceeds the heat production due to the irreversible losses, and thatthe main part of heat evolved at the cathode is...

  15. Comparison of heat transfer efficiency between heat pipe and tube bundles heat exchanger

    OpenAIRE

    Wu Zhao-Chun; Zhu Xiang-Ping

    2015-01-01

    A comparison of heat transfer efficiency between the heat pipe and tube bundles heat exchanger is made based on heat transfer principle and the analysis of thermal characteristics. This paper argues that although heat pipe has the feature of high axial thermal conductivity, to those cases where this special function of heat transfer is unnecessary, heat pipe exchanger is not a high efficient heat exchanger when it is just used as a conventional heat exchang...

  16. Space Heating Equipment

    Energy Technology Data Exchange (ETDEWEB)

    Rafferty, Kevin D.

    1998-01-01

    The performance evaluation of space heating equipment for a geothermal application is generally considered from either of two perspectives: (a) selecting equipment for installation in new construction, or (b) evaluating the performance and retrofit requirements of an existing system. With regard to new construction, the procedure is relatively straightforward. Once the heating requirements are determined, the process need only involve the selection of appropriately sized hot water heating equipment based on the available water temperature. It is important to remember that space heating equipment for geothermal applications is the same equipment used in non-geothermal applications. What makes geothermal applications unique is that the equipment is generally applied at temperatures and flow rates that depart significantly from traditional heating system design. This chapter presents general considerations for the performance of heating equipment at non-standard temperature and flow conditions, retrofit of existing systems, and aspects of domestic hot water heating.

  17. District heating versus local heating - Social supportability

    International Nuclear Information System (INIS)

    District heating, DH, is an energy source which can provide a cost-effective, environmentally friendly source of heat and power for cities, but only in the case of well running systems, with reasonable technological losses. The benefits of DH system are well known: environmental friendly, energy security, economic and social advantages. DH already covers 60% of heating and hot water needs in transition economies. Today, 70 % of Russian, Latvian and Belarus homes use DH, and heating accounts for one-third of total Russian energy consumption. Yet a large number of DH systems in the region face serious financial, marketing or technical problems because of the policy framework. How can DH issues be best addressed in national and local policy? What can governments do to create the right conditions for the sustainable development of DH while improving service quality? What policies can help capture the economic, environmental and energy security benefits of co-generation and DH? To address these questions, the International Energy Agency (IEA) hosted in 2002 and 2004 conference focusing on the crucial importance of well-designed DH policies, for exchanging information on policy approaches. The conclusions of the conference have shown that 'DH systems can do much to save energy and boost energy security, but stronger policy measures are needed to encourage wise management and investment. With a stronger policy framework, DH systems in formerly socialist countries could save the equivalent of 80 billion cubic meters of natural gas a year through supply side efficiency improvements. This is greater than total annual natural gas consumption in Italy'. More efficient systems will also decrease costs, reducing household bills and making DH competitive on long-term. This paper presents the issues: -Theoretical benefits of the district heating and cooling systems; - Municipal heating in Romania; - Technical and economic problems of DH systems and social supportability; - How

  18. Absorption heat pumps

    Science.gov (United States)

    Huhtinen, M.; Heikkilae, M.; Andersson, R.

    1987-03-01

    The aim of the study was to analyze the technical and economic feasibility of absorption heat pumps in Finland. The work was done as a case study: the technical and economic analyses have been carried out for six different cases, where in each the suitable size and type of the heat pump plant and the auxiliary components and connections were specified. The study also detailed the costs concerning the procurement, installation and test runs of the machinery, as well as the savings in energy costs incurred by the introduction of the plant. Conclusions were drawn of the economic viability of the applications studied. The following cases were analyzed: heat recovery from flue gases and productin of district heat in plants using peat, natural gas, and municipal wastes as a fuel. Heat recovery in the pulp and paper industry for the upgrading of pressure of secondary steam and for the heating of white liquor and combustion and drying the air. Heat recovery in a peat-fulled heat and power plant from flue gases that have been used for the drying of peat. According to the study, the absorption heat pump suits best to the production of district heat, when the heat source is the primary energy is steam produced by the boiler. Included in the flue as condensing is the purification of flue gases. Accordingly, benefit is gained on two levels in thick applications. In heat and power plants the use of absorption heat pumps is less economical, due to the fact that the steam used by the pump reduces the production of electricity, which is rated clearly higher than heat.

  19. Experimental research on heat transfer in a coupled heat exchanger

    OpenAIRE

    Liu Yin; Ma Jing; Zhou Guang-Hui; Guan Ren-Bo

    2013-01-01

    The heat exchanger is a devise used for transferring thermal energy between two or more different temperatures. The widespreadly used heat exchanger can only achieve heat exchange between two substances. In this paper, a coupled heat exchanger is proposed, which includes a finned heat exchanger and a double pipe heat exchanger, for multiple heat exchange simultaneously. An experiment is conducted, showing that the average heating capacity increases more tha...

  20. Heat pipe cooling system with sensible heat sink

    Science.gov (United States)

    Silverstein, Calvin C.

    1988-01-01

    A heat pipe cooling system which employs a sensible heat sink is discussed. With this type of system, incident aerodynamic heat is transported via a heat pipe from the stagnation region to the heat sink and absorbed by raising the temperature of the heat sink material. The use of a sensible heat sink can be advantageous for situations where the total mission heat load is limited, as it is during re-entry, and a suitable radiation sink is not available.

  1. 24 CFR 3280.506 - Heat loss/heat gain.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Heat loss/heat gain. 3280.506... URBAN DEVELOPMENT MANUFACTURED HOME CONSTRUCTION AND SAFETY STANDARDS Thermal Protection § 3280.506 Heat loss/heat gain. The manufactured home heat loss/heat gain shall be determined by methods outlined...

  2. Optimization of Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Ivan Catton

    2010-10-01

    The objective of this research is to develop tools to design and optimize heat exchangers (HE) and compact heat exchangers (CHE) for intermediate loop heat transport systems found in the very high temperature reator (VHTR) and other Generation IV designs by addressing heat transfer surface augmentation and conjugate modeling. To optimize heat exchanger, a fast running model must be created that will allow for multiple designs to be compared quickly. To model a heat exchanger, volume averaging theory, VAT, is used. VAT allows for the conservation of mass, momentum and energy to be solved for point by point in a 3 dimensional computer model of a heat exchanger. The end product of this project is a computer code that can predict an optimal configuration for a heat exchanger given only a few constraints (input fluids, size, cost, etc.). As VAT computer code can be used to model characteristics )pumping power, temperatures, and cost) of heat exchangers more quickly than traditional CFD or experiment, optimization of every geometric parameter simultaneously can be made. Using design of experiment, DOE and genetric algorithms, GE, to optimize the results of the computer code will improve heat exchanger disign.

  3. Heating load, heating-load density and COP optimizations of an endoreversible air heat-pump

    International Nuclear Information System (INIS)

    The finite-time thermodynamic performance has been studied of an endoreversible air heat-pump with constant-temperature heat-reservoirs. The heating load, the coefficient of performance (COP), and the heating-load density, i.e. the ratio of heating load to the maximum specific volume in the cycle, are the optimization objectives. The analytical formulae relating the heating load and pressure-ratio, between the COP and pressure-ratio, as well as between the heating-load density and pressure-ratio are derived assuming heat resistance losses occur in the hot- and cold-side heat-exchangers. The influences of the effectiveness of the heat-exchangers and the heat-reservoir temperature-ratio on the heating load, the COP and the heating-load density are analyzed. The cycle performance optimizations are performed by searching the optimal distribution of heat conductance of the hot- and cold-side heat-exchangers for the fixed total heat-exchanger inventory. The influences of some design parameters, including heat-capacity rate of the working fluid, heat-reservoir temperature-ratio and heat-exchanger inventory on the optimal distribution of heat conductance, the maximum heating load and the maximum heating-load density are indicated by numerical examples. The different results obtained from the heating-load optimization and the heating-load density optimization are shown. The air heat-pump design, with heat-loading density optimization, leads to smaller size equipment

  4. Silicon Heat Pipe Array

    Science.gov (United States)

    Yee, Karl Y.; Ganapathi, Gani B.; Sunada, Eric T.; Bae, Youngsam; Miller, Jennifer R.; Beinsford, Daniel F.

    2013-01-01

    Improved methods of heat dissipation are required for modern, high-power density electronic systems. As increased functionality is progressively compacted into decreasing volumes, this need will be exacerbated. High-performance chip power is predicted to increase monotonically and rapidly with time. Systems utilizing these chips are currently reliant upon decades of old cooling technology. Heat pipes offer a solution to this problem. Heat pipes are passive, self-contained, two-phase heat dissipation devices. Heat conducted into the device through a wick structure converts the working fluid into a vapor, which then releases the heat via condensation after being transported away from the heat source. Heat pipes have high thermal conductivities, are inexpensive, and have been utilized in previous space missions. However, the cylindrical geometry of commercial heat pipes is a poor fit to the planar geometries of microelectronic assemblies, the copper that commercial heat pipes are typically constructed of is a poor CTE (coefficient of thermal expansion) match to the semiconductor die utilized in these assemblies, and the functionality and reliability of heat pipes in general is strongly dependent on the orientation of the assembly with respect to the gravity vector. What is needed is a planar, semiconductor-based heat pipe array that can be used for cooling of generic MCM (multichip module) assemblies that can also function in all orientations. Such a structure would not only have applications in the cooling of space electronics, but would have commercial applications as well (e.g. cooling of microprocessors and high-power laser diodes). This technology is an improvement over existing heat pipe designs due to the finer porosity of the wick, which enhances capillary pumping pressure, resulting in greater effective thermal conductivity and performance in any orientation with respect to the gravity vector. In addition, it is constructed of silicon, and thus is better

  5. Electricity and heat production

    International Nuclear Information System (INIS)

    Bohunice NPPs fulfilled planned power supply to 103.4% in 1997 having supplied 9,968,758 MWh to the national power grid. Bohunice NPPs power generation reached 10,796,904 MWh which represented 51% share of Slovak power stations plc power generation and 44% of national power generation. Total Bohunice NPPs production represented 178,715,793 MWh of power since the start-up of their WWER 440 units. Together with the A-1 plant it represented 180,180,372 MWh in total since the Bohunice site had been commissioned. Heat supply for heating purposes to the town of Trnava was reliable and met customer's requirements representing the amount of 1,003,500 GJ of heat, which was by 221,173 GJ less than in 1996. The heat supply to Trnava decreased due to the heat line from 13 May to 3 October 1997, due to starting the heat line to the towns of Hlohovec and Leopoldov up, and due to warmer weather during the heating season. The heat supply to Trnava represented 8,787,323 GJ since the Bohunice-Trnava heat line had been started up (December 1997). The Heat Transmission Plant Jaslovske Bohunice caught 65,687 GJ of heat last year which represented 310,982 GJ since its start-up (November 1992). Total heat supply from nuclear sources for heating purposes was 1,691,052 GJ in 1997, which represented 16,495,333 GJ since the Transmission Plant had been started up. Performance indicators from the beginning of operation to the end of 1997 and performance indicators in 1997 as well as operation history of Bohunice 1 - 4 reactor are presented

  6. Heat transfer from oriented heat exchange areas

    Science.gov (United States)

    Vantuch, Martin; Huzvar, Jozef; Kapjor, Andrej

    2014-03-01

    This paper deals with the transfer of heat-driven heat transfer surface area in relation to the construction of the criterion equation for "n" horizontal pipe one about another. On the bases of theoretical models have been developed for calculating the thermal performance of natural convection by Churilla and Morgan, for various pipe diameters and temperatures. These models were compared with models created in CFD-Fluent Ansys the same boundary conditions. The aim of the analyse of heat and fluxional pipe fields "n" pipes one about another at natural convection is the creation of criterion equation on the basis of which the heat output of heat transfer from pipe oriented areas one above another with given spacing could be quantified. At presence a sum of criterion equations exists for simple geometrical shapes of individual oriented geometrical areas but the criterion equation which would consider interaction of fluxional field generated by free convection from multiple oriented areas is not mentioned in standardly accessible technical literature and other magazine publications.

  7. Floor heating maximizes residents` comfort

    Energy Technology Data Exchange (ETDEWEB)

    Tirkkanen, P.; Wikstroem, T.

    1996-11-01

    Storing heat in floors by using economical night-time electricity does not increase the specific consumption of heating. According to studies done by IVO, the optimum housing comfort is achieved if the room is heated mainly by means of floor heating that is evened out by window or ceiling heating, or by a combination of all three forms of heating. (orig.)

  8. Support for heat exchangers

    International Nuclear Information System (INIS)

    The very large heat exchangers which are typical of many nuclear power plants place great demands on their supports. The support here described is for a vertical heat exchanger. A convex Lubrit plate allows a certain amount of transverse and rotational movement of the heat exhanger relative to the foundation. Taps engaging in the support surface of the heat exchanger and between the support box and the concrete foundation ensure that relative movement is restricted to those surfaces where it is intended. A steel box structure embedded in the concrete foundation dissipates heat transferred through the support system and avoids overheating the concrete. Horizontal stays support the heat exchanger against the concrete walls. (JIW)

  9. HEAT TRANSFER FLUIDS

    OpenAIRE

    Lenert, Andrej; Nam, Youngsuk; Wang, Evelyn N.

    2012-01-01

    The choice of heat transfer fluids has significant effects on the performance, cost, and reliability of solar thermal systems. In this chapter, we evaluate existing heat transfer fluids such as oils and molten salts based on a new figure of merit capturing the combined effects of thermal storage capacity, convective heat transfer characteristics, and hydraulic performance of the fluids. Thermal stability, freezing point, and safety issues are also discussed. Through a comparative analysis, we...

  10. Convection heat transfer

    CERN Document Server

    Bejan, Adrian

    2013-01-01

    Written by an internationally recognized authority on heat transfer and thermodynamics, this second edition of Convection Heat Transfer contains new and updated problems and examples reflecting real-world research and applications, including heat exchanger design. Teaching not only structure but also technique, the book begins with the simplest problem solving method (scale analysis), and moves on to progressively more advanced and exact methods (integral method, self similarity, asymptotic behavior). A solutions manual is available for all problems and exercises.

  11. Mechanisms of Coronal Heating

    Indian Academy of Sciences (India)

    S. R. Verma

    2006-06-01

    The Sun is a mysterious star. The high temperature of the chromosphere and corona present one of the most puzzling problems of solar physics. Observations show that the solar coronal heating problem is highly complex with many different facts. It is likely that different heating mechanisms are at work in solar corona. Recent observations show that Magnetic Carpet is a potential candidate for solar coronal heating.

  12. NCSX Plasma Heating Methods

    Energy Technology Data Exchange (ETDEWEB)

    H.W. Kugel; D. Spong; R. Majeski; M. Zarnstorff

    2003-02-28

    The NCSX (National Compact Stellarator Experiment) has been designed to accommodate a variety of heating systems, including ohmic heating, neutral-beam injection, and radio-frequency. Neutral beams will provide one of the primary heating methods for NCSX. In addition to plasma heating, beams are also expected to provide a means for external control over the level of toroidal plasma rotation velocity and its profile. The plan is to provide 3 MW of 50 keV balanced neutral-beam tangential injection with pulse lengths of 500 msec for initial experiments, and to be upgradeable to pulse lengths of 1.5 sec. Subsequent upgrades will add 3 MW of neutral-beam injection. This Chapter discusses the NCSX neutral-beam injection requirements and design issues, and shows how these are provided by the candidate PBX-M (Princeton Beta Experiment-Modification) neutral-beam injection system. In addition, estimations are given for beam-heating efficiencies, scaling of heating efficiency with machine size an d magnetic field level, parameter studies of the optimum beam-injection tangency radius and toroidal injection location, and loss patterns of beam ions on the vacuum chamber wall to assist placement of wall armor and for minimizing the generation of impurities by the energetic beam ions. Finally, subsequent upgrades could add an additional 6 MW of radio-frequency heating by mode-conversion ion-Bernstein wave (MCIBW) heating, and if desired as possible future upgrades, the design also will accommodate high-harmonic fast-wave and electron-cyclotron heating. The initial MCIBW heating technique and the design of the radio-frequency system lend themselves to current drive, so that if current drive became desirable for any reason only minor modifications to the heating system described here would be needed. The radio-frequency system will also be capable of localized ion heating (bulk or tail), and possibly ion-Bernstein-wave-generated sheared flows.

  13. Heat and thermodynamics

    CERN Document Server

    Saxena, A K

    2014-01-01

    Heat and thermodynamics aims to serve as a textbook for Physics, Chemistry and Engineering students. The book covers basic ideas of Heat and Thermodynamics, Kinetic Theory and Transport Phenomena, Real Gases, Liquafaction and Production and Measurement of very Low Temperatures, The First Law of Thermodynamics, The Second and Third Laws of Thermodynamics and Heat Engines and Black Body Radiation. KEY FEATURES Emphasis on concepts Contains 145 illustrations (drawings), 9 Tables and 48 solved examples At the end of chapter exercises and objective questions

  14. Counterflow Regolith Heat Exchanger

    Science.gov (United States)

    Zubrin, Robert; Jonscher, Peter

    2013-01-01

    A problem exists in reducing the total heating power required to extract oxygen from lunar regolith. All such processes require heating a great deal of soil, and the heat energy is wasted if it cannot be recycled from processed material back into new material. The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat exchanger with internal and external augers attached to the inner rotating tube to move the regolith. Hot regolith in the outer tube is moved in one direction by a right-hand - ed auger, and the cool regolith in the inner tube is moved in the opposite direction by a left-handed auger attached to the inside of the rotating tube. In this counterflow arrangement, a large fraction of the heat from the expended regolith is transferred to the new regolith. The spent regolith leaves the heat exchanger close to the temperature of the cold new regolith, and the new regolith is pre-heated close to the initial temperature of the spent regolith. Using the CoRHE can reduce the heating requirement of a lunar ISRU system by 80%, reducing the total power consumption by a factor of two. The unique feature of this system is that it allows for counterflow heat exchange to occur between solids, instead of liquids or gases, as is commonly done. In addition, in variants of this concept, the hydrogen reduction can be made to occur within the counterflow heat exchanger itself, enabling a simplified lunar ISRU (in situ resource utilization) system with excellent energy economy and continuous nonbatch mode operation.

  15. Microplate Heat Exchanger Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a microplate heat exchanger for cryogenic cooling systems used for continuous flow distributed cooling systems, large focal plane arrays, multiple...

  16. Heat Pipe Materials Compatibility

    Science.gov (United States)

    Eninger, J. E.; Fleischman, G. L.; Luedke, E. E.

    1976-01-01

    An experimental program to evaluate noncondensable gas generation in ammonia heat pipes was completed. A total of 37 heat pipes made of aluminum, stainless steel and combinations of these materials were processed by various techniques, operated at different temperatures and tested at low temperature to quantitatively determine gas generation rates. In order of increasing stability are aluminum/stainless combination, all aluminum and all stainless heat pipes. One interesting result is the identification of intentionally introduced water in the ammonia during a reflux step as a means of surface passivation to reduce gas generation in stainless-steel/aluminum heat pipes.

  17. Heat rejection system

    Science.gov (United States)

    Smith, Gregory C.; Tokarz, Richard D.; Parry, Jr., Harvey L.; Braun, Daniel J.

    1980-01-01

    A cooling system for rejecting waste heat consists of a cooling tower incorporating a plurality of coolant tubes provided with cooling fins and each having a plurality of cooling channels therein, means for directing a heat exchange fluid from the power plant through less than the total number of cooling channels to cool the heat exchange fluid under normal ambient temperature conditions, means for directing water through the remaining cooling channels whenever the ambient temperature rises above the temperature at which dry cooling of the heat exchange fluid is sufficient and means for cooling the water.

  18. Heat Capacity Analysis Report

    International Nuclear Information System (INIS)

    The purpose of this report is to provide heat capacity values for the host and surrounding rock layers for the waste repository at Yucca Mountain. The heat capacity representations provided by this analysis are used in unsaturated zone (UZ) flow, transport, and coupled processes numerical modeling activities, and in thermal analyses as part of the design of the repository to support the license application. Among the reports that use the heat capacity values estimated in this report are the ''Multiscale Thermohydrologic Model'' report, the ''Drift Degradation Analysis'' report, the ''Ventilation Model and Analysis Report, the Igneous Intrusion Impacts on Waste Packages and Waste Forms'' report, the ''Dike/Drift Interactions report, the Drift-Scale Coupled Processes (DST and TH Seepage) Models'' report, and the ''In-Drift Natural Convection and Condensation'' report. The specific objective of this study is to determine the rock-grain and rock-mass heat capacities for the geologic stratigraphy identified in the ''Mineralogic Model (MM3.0) Report'' (BSC 2004 [DIRS 170031], Table 1-1). This report provides estimates of the heat capacity for all stratigraphic layers except the Paleozoic, for which the mineralogic abundance data required to estimate the heat capacity are not available. The temperature range of interest in this analysis is 25 C to 325 C. This interval is broken into three separate temperature sub-intervals: 25 C to 95 C, 95 C to 114 C, and 114 C to 325 C, which correspond to the preboiling, trans-boiling, and postboiling regimes. Heat capacity is defined as the amount of energy required to raise the temperature of a unit mass of material by one degree (Nimick and Connolly 1991 [DIRS 100690], p. 5). The rock-grain heat capacity is defined as the heat capacity of the rock solids (minerals), and does not include the effect of water that exists in the rock pores. By comparison, the rock-mass heat capacity considers the heat capacity of both solids and pore

  19. Heat transfer dynamics

    International Nuclear Information System (INIS)

    As heat transfer technology increases in complexity, it becomes more difficult for those without thermal dynamics engineering training to choose between competitive heat transfer systems offered to meet their drying requirements. A step back to the basics of heat transfer can help professional managers and papermakers make informed decisions on alternative equipment and methods. The primary forms of heat and mass transfer are reviewed with emphasis on the basics, so a practical understanding of each is gained. Finally, the principles and benefits of generating infrared energy by combusting a gaseous hydrocarbon fuel are explained

  20. Heat pipe technology issues

    International Nuclear Information System (INIS)

    Critical high temperature, high power applications in space nuclear power designs are near the current state of the art of heat pipe technology in terms of power density, operating temperature, and lifetime. Recent heat pipe development work at Los Alamos National Laboratory has involved performance testing of typical space reactor heat pipe designs to power levels in excess of 19 kW/cm2 axially and 300 W/cm2 radially at temperatures in the 1400 to 1500 K range. Operation at conditions in the 10 kW/cm2 range has been sustained for periods of up to 1000 hours without evidence of performance degradation. The effective length for heat transport in these heat pipes was from 1.0 to 1.5 M. Materials used were molybdenum alloys with lithium employed as the heat pipe operating fluid. Shorter, somewhat lower power, molybdenum heat pipes have been life tested at Los Alamos for periods of greater than 25,000 hours at 1700 K with lithium and 20,000 hours at 15000K with sodium. These life test demonstrations and the attendant performance limit investigations provide an experimental basis for heat pipe application in space reactor design and represent the current state-of-the-art of high temperature heat pipe technology

  1. Mesoscopic photon heat transistor

    DEFF Research Database (Denmark)

    Ojanen, T.; Jauho, Antti-Pekka

    2008-01-01

    We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir-Wingreen-Landauer-typ......We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir...

  2. Introduction to Heat Pipes

    Science.gov (United States)

    Ku, Jentung

    2015-01-01

    This is the presentation file for the short course Introduction to Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. NCTS 21070-15. Course Description: This course will present operating principles of the heat pipe with emphases on the underlying physical processes and requirements of pressure and energy balance. Performance characterizations and design considerations of the heat pipe will be highlighted. Guidelines for thermal engineers in the selection of heat pipes as part of the spacecraft thermal control system, testing methodology, and analytical modeling will also be discussed.

  3. Heating uranium alloy billets

    International Nuclear Information System (INIS)

    Data were obtained for the surface heat transfer coefficient of uranium and the alloys of uranium-0.75 wt percent titanium, uranium-6 wt percent niobium, and uranium-7.5 wt percent niobium-2.5 wt percent zirconium. Samples were heated to 8500C in both a molten salt bath and an argon-purged air furnace, then the samples were cooled in air. Surface heat transfer coefficients were calculated from the experimental data for both heating and cooling of the metals. 4 fig, 4 tables

  4. Lunar Base Heat Pump

    Science.gov (United States)

    Walker, D.; Fischbach, D.; Tetreault, R.

    1996-01-01

    The objective of this project was to investigate the feasibility of constructing a heat pump suitable for use as a heat rejection device in applications such as a lunar base. In this situation, direct heat rejection through the use of radiators is not possible at a temperature suitable for lde support systems. Initial analysis of a heat pump of this type called for a temperature lift of approximately 378 deg. K, which is considerably higher than is commonly called for in HVAC and refrigeration applications where heat pumps are most often employed. Also because of the variation of the rejection temperature (from 100 to 381 deg. K), extreme flexibility in the configuration and operation of the heat pump is required. A three-stage compression cycle using a refrigerant such as CFC-11 or HCFC-123 was formulated with operation possible with one, two or three stages of compression. Also, to meet the redundancy requirements, compression was divided up over multiple compressors in each stage. A control scheme was devised that allowed these multiple compressors to be operated as required so that the heat pump could perform with variable heat loads and rejection conditions. A prototype heat pump was designed and constructed to investigate the key elements of the high-lift heat pump concept. Control software was written and implemented in the prototype to allow fully automatic operation. The heat pump was capable of operation over a wide range of rejection temperatures and cooling loads, while maintaining cooling water temperature well within the required specification of 40 deg. C +/- 1.7 deg. C. This performance was verified through testing.

  5. Passive Vaporizing Heat Sink

    Science.gov (United States)

    Knowles, TImothy R.; Ashford, Victor A.; Carpenter, Michael G.; Bier, Thomas M.

    2011-01-01

    A passive vaporizing heat sink has been developed as a relatively lightweight, compact alternative to related prior heat sinks based, variously, on evaporation of sprayed liquids or on sublimation of solids. This heat sink is designed for short-term dissipation of a large amount of heat and was originally intended for use in regulating the temperature of spacecraft equipment during launch or re-entry. It could also be useful in a terrestrial setting in which there is a requirement for a lightweight, compact means of short-term cooling. This heat sink includes a hermetic package closed with a pressure-relief valve and containing an expendable and rechargeable coolant liquid (e.g., water) and a conductive carbon-fiber wick. The vapor of the liquid escapes when the temperature exceeds the boiling point corresponding to the vapor pressure determined by the setting of the pressure-relief valve. The great advantage of this heat sink over a melting-paraffin or similar phase-change heat sink of equal capacity is that by virtue of the =10x greater latent heat of vaporization, a coolant-liquid volume equal to =1/10 of the paraffin volume can suffice.

  6. Introductory heat-transfer

    Science.gov (United States)

    Widener, Edward L.

    1992-01-01

    The objective is to introduce some concepts of thermodynamics in existing heat-treating experiments using available items. The specific objectives are to define the thermal properties of materials and to visualize expansivity, conductivity, heat capacity, and the melting point of common metals. The experimental procedures are described.

  7. Heat exchangers: operation problems

    International Nuclear Information System (INIS)

    The main operation problems for heat exchangers are fouling, corrosion, vibrations and mechanical resistance. Fouling and corrosion lead to an over dimensioning, energy consumption increase, corroded pieces change, shutdown costs. Vibrations are taken in account during the dimensioning phase of the heat exchangers. Mechanical resistance problems are, for the classical ones, described in regulation texts. (A.B.). 5 figs., 4 tabs

  8. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... So Long? Admission to the Hospital Heroes on Medicine's Front Line Observation Emergency Care Fact Sheet ... Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at Mercy Health System in Chesterfield, Missouri Heat-related illness can be ...

  9. Heat pipe technology issues

    International Nuclear Information System (INIS)

    Recent heat pipe development work at Los Alamos National Laboratory as involved performance testing of typical space reactor heat pipe designs to power levels in excess of 19 kW/cm2 axially and 300 W/cm2 radially at temperatures in the 1400 to 15000K range. Operation at conditions in the 10 kW/cm2 range has been sustained for periods of up to 1000 hours without evidence of performance degradation. The effective length for heat transport in these heat pipes was from 1.0 to 1.5 M. Materials used were molybdenum alloys with lithium employed as the heat pipe operating fluid. Shorter, somewhat lower power density, molybdenum heat pipes have been life tested at Los Alamos for periods of greater than 25,000 hours at 17000K with lithium and 20,000 hours at 15000K with sodium. These life test demonstrations and the attendant performance limit investigations provide an experimental basis for heat pipe application in space reactor design and represent the current state-of-the-art of high temperature heat pipe technology. 9 refs., 11 figs

  10. Radioisotopic heat source

    International Nuclear Information System (INIS)

    Disclosed is a radioisotopic heat source and method for a long life electrical generator. The source includes plutonium dioxide shards and yttrium or hafnium in a container of tantalum-tungsten-hafnium alloy, all being in a nickel alloy outer container, and subjected to heat treatment of from about 15700F to about 17200F for about one h

  11. Solar Heating System with Building-Integrated Heat Storage

    DEFF Research Database (Denmark)

    Heller, Alfred

    1996-01-01

    Traditional solar heating systems cover between 5 and 10% of the heat demand fordomestic hot water and comfort heating. By applying storage capacity this share can beincreased much. The Danish producer of solar heating systems, Aidt-Miljø, markets such a system including storage of dry sand heated...... by PP-pipe heat exchanger. Heat demand is reduced due to direct solar heating, and due to storage. Heat demand is reduced due to direct solar heating, due to storage and due to lower heat losses through the ground. In theory, by running the system flow backwards through the sand storage, active heating...... can be achieved.The objective of the report is to present results from measured system evaluation andcalculations and to give guidelines for the design of such solar heating systems with building integrated sand storage. The report is aimed to non-technicians. In another report R-006 the main results...

  12. Process heat reactors

    International Nuclear Information System (INIS)

    The consumption of heat, for industrial and domestic needs, takes up half of the national energy supply; direct utilization of the heat produced by nuclear reactors could therefore contribute to reduce the deficit in the energetic results. The restraints proper to heat consumption (dispersal and variety of consumers, irregular demand) involve the development of the heat transport system structures and adequate nuclear reactors. With this in view, the Commissariat a l'Energie Atomique and Technicatome are developing the CAS reactor series, pressurized water reactors (PWR), (CAS 3G reactor with a power of 420 MW.th.), and the Thermos reactor (100 MW.th.), directly conceived to produce heat at 1200C and whose technology derives from the experimental pool reactors type. In order to prove the value of the Thermos design, an experimental reactor should soon be constructed in the Saclay nuclear research centre

  13. ICRF heating in DIVA

    International Nuclear Information System (INIS)

    ICRF Heating of impurity-free tokamak plasmas has been studied in DIVA. The frequency is fixed at 25 MHz, which is a second harmonic cyclotron frequency of deuterons with a toroidal magnetic field of 16.4 kG. (1) Optimum heating conditions were investigated in varying the toroidal magnetic field B sub( t) and the proton-to-deuteron density ratio epsilon sub(p). The most favorable ion heating is observed for B sub( t) -- 18 kG and epsilon sub(p) = 5 -- 10%, which is explained by two-ion hybrid effects. (2) In heating results after improvement of the coupling structure, the ion heating efficiency is raised from 40% to almost 100%. Bulk ion temperature increased by a factor of 2.7 in application of the rf net power of 180 kW including the circuit loss. (author)

  14. Heat Pipe Systems

    Science.gov (United States)

    1993-01-01

    The heat pipe was developed to alternately cool and heat without using energy or any moving parts. It enables non-rotating spacecraft to maintain a constant temperature when the surface exposed to the Sun is excessively hot and the non Sun-facing side is very cold. Several organizations, such as Tropic-Kool Engineering Corporation, joined NASA in a subsequent program to refine and commercialize the technology. Heat pipes have been installed in fast food restaurants in areas where humid conditions cause materials to deteriorate quickly. Moisture removal was increased by 30 percent in a Clearwater, FL Burger King after heat pipes were installed. Relative humidity and power consumption were also reduced significantly. Similar results were recorded by Taco Bell, which now specifies heat pipe systems in new restaurants in the Southeast.

  15. Advanced heat pump

    Science.gov (United States)

    Ashley, Joseph L.; Matthews, John D.

    1989-09-01

    This patent application discloses a heat pump which includes a first packed bed of liquid desiccant for removing moisture from outside air in the heating mode of operation, and a pump for transferring the moisture laden desiccant to a second packed bed which humidifies condenser heated inside air by adding water vapor to the air. The first packed bed, by removing moisture from the outside air before it passes through the heat pump's evaporator coils, prevents frost from forming on the coils. In the cooling mode of operation the second packed bed of liquid desiccant removes water vapor from the air inside of the building. The moisture laden desiccant is then transferred to the first packed bed by a second pump where condenser heat transfers the moisture from the desiccant to outside air.

  16. Heat pipes and use of heat pipes in furnace exhaust

    Science.gov (United States)

    Polcyn, Adam D.

    2010-12-28

    An array of a plurality of heat pipe are mounted in spaced relationship to one another with the hot end of the heat pipes in a heated environment, e.g. the exhaust flue of a furnace, and the cold end outside the furnace. Heat conversion equipment is connected to the cold end of the heat pipes.

  17. An important feature of air heat pump cycle: Heating capacity in line with heating load

    International Nuclear Information System (INIS)

    In the conventional vapor-compression heat pumps, the heating capacity and the heating load usually vary in opposite directions, which results in a mismatch of the heating capacity and the heating load at off-design conditions. Air (reversed Brayton) cycle is a potential substitute for the conventional vapor-compression cycles. This paper proved that in theory the air heat pump cycle can make the heating capacity in line with the heating load at a stable level of heating COP (coefficient of performance). A thermodynamic model for the air heat pump cycle with practical compressor and expander was developed. The optimal heating COP and the corresponding pressure ratio were derived from the model. Then the cycle performance was analytically expressed under the optimal COP conditions. The heating capacity under different operating conditions was found in line with the heating load. Comparisons between the air heat pump cycle and two typical vapor-compression heat pump cycles were numerically done for further verification. It also turned out that the energy efficiency of air heat pump is comparable to the transcritical CO2 heat pump, particularly at large temperature difference. - Highlights: • We developed a thermodynamic model for air heat pump cycle. • The optimal COP (coefficient of performance) was derived and the corresponding cycle performance was analyzed. • Comparison of air heat pump cycle and vapor-compression cycles was numerically done. • We proved air heat pump cycle can make heating capacity in line with heating load

  18. Acoustically enhanced heat transport

    Energy Technology Data Exchange (ETDEWEB)

    Ang, Kar M.; Hung, Yew Mun; Tan, Ming K., E-mail: tan.ming.kwang@monash.edu [School of Engineering, Monash University Malaysia, 47500 Bandar Sunway, Selangor (Malaysia); Yeo, Leslie Y. [Micro/Nanophysics Research Laboratory, RMIT University, Melbourne, VIC 3001 (Australia); Friend, James R. [Department of Mechanical and Aerospace Engineering, University of California, San Diego, California 92093 (United States)

    2016-01-15

    We investigate the enhancement of heat transfer in the nucleate boiling regime by inducing high frequency acoustic waves (f ∼ 10{sup 6} Hz) on the heated surface. In the experiments, liquid droplets (deionized water) are dispensed directly onto a heated, vibrating substrate. At lower vibration amplitudes (ξ{sub s} ∼ 10{sup −9} m), the improved heat transfer is mainly due to the detachment of vapor bubbles from the heated surface and the induced thermal mixing. Upon increasing the vibration amplitude (ξ{sub s} ∼ 10{sup −8} m), the heat transfer becomes more substantial due to the rapid bursting of vapor bubbles happening at the liquid-air interface as a consequence of capillary waves travelling in the thin liquid film between the vapor bubble and the air. Further increases then lead to rapid atomization that continues to enhance the heat transfer. An acoustic wave displacement amplitude on the order of 10{sup −8} m with 10{sup 6} Hz order frequencies is observed to produce an improvement of up to 50% reduction in the surface temperature over the case without acoustic excitation.

  19. Fluidised bed heat exchangers

    International Nuclear Information System (INIS)

    Problems that have arisen during the initial stages of development of fluidised bed boilers in which heat transfer surfaces are immersed in fluidised solids are discussed. The very high heat transfer coefficients that are obtained under these conditions can be exploited to reduce the total heat transfer surface to a fraction of that in normal boilers. However, with the high heat flux levels involved, tube stressing becomes more important and it is advantageous to use smaller diameter tubes. One of the initial problems was that the pumping power absorbed by the fluidised bed appeared to be high. The relative influence of the fluidising velocity (and the corresponding bed area), tube diameter, tube spacing, heat transfer coefficient and bed temperature on pumping power and overall cost was determined. This showed the importance of close tube packing and research was undertaken to see if this would adversely affect the heat transfer coefficient. Pressure operation also reduces the pumping power. Fouling and corrosion tests in beds burning coal suggest that higher temperatures could be reached reliably and cost studies show that, provided the better refractory metals are used, the cost of achieving higher temperatures is not unduly high. It now remains to demonstrate at large scale that the proposed systems are viable and that the methods incorporated to overcome start up and part lead running problems are satisfactory. The promising role of these heat transfer techniques in other applications is briefly discussed

  20. Heat recovery apparatus

    International Nuclear Information System (INIS)

    Heat transfer is a living science and technical advances are constantly being made. However, in many cases, progress is limited by the equipment that is available on the market, rather than by knowledge of the heat transfer process. A case in point is the design of economizers: in such equipment a small quantity of water (with a relatively good heat transfer coefficient) is heated by a large quantity of low-pressure gas (with an inherently low heat transfer coefficient). As a first step in design finned tubing is used to lessen the discrepancy in coefficients. From this point, it becomes apparent that the equipment consists of a small number of tubes (to maintain good velocity on the water side) of considerable length (to provide sufficient area). In the process industries the base pressure, though low, may be in the region of 0.5 bar, and there is no convenient flue in which to place the heat recovery coil. It is therefore contained in a flat-sided enclosure, which is ill-fitted to pressure containment and is therefore reinforced with a plethora of structural sections. Such inelegant construction is quite common in North America; in Europe, cylindrical containments of vast size have been supplied for the same purposes. The real shortcoming is a successful marriage of different disciplines to produce reliable and efficient heat transfer equipment suitably contained

  1. Chapter 11. Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Rafferty, Kevin D.; Culver, Gene

    1998-01-01

    Most geothermal fluids, because of their elevated temperature, contain a variety of dissolved chemicals. These chemicals are frequently corrosive toward standard materials of construction. As a result, it is advisable in most cases to isolate the geothermal fluid from the process to which heat is being transferred. The task of heat transfer from the geothermal fluid to a closed process loop is most often handled by a plate heat exchanger. The two most common types used in geothermal applications are: bolted and brazed. For smaller systems, in geothermal resource areas of a specific character, downhole heat exchangers (DHEs) provide a unique means of heat extraction. These devices eliminate the requirement for physical removal of fluid from the well. For this reason, DHE-based systems avoid entirely the environmental and practical problems associated with fluid disposal. Shell and tube heat exchangers play only a minor role in low-temperature, direct-use systems. These units have been in common use in industrial applications for many years and, as a result, are well understood. For these reasons, shell and tube heat exchangers will not be covered in this chapter.

  2. Soil Heat Flow Model

    Science.gov (United States)

    Varas, E.; Nunez, C.; Meza, F. J.

    2008-12-01

    The Penman-Monteith method for estimating evapotranspiration (ET) has been recommended by FAO. This method requires measures of temperature, wind speed, relative humidity and heat flow in the soil. This last variable is rarely available. Soil heat flow is generally small compared to the net radiation, and many times is ignored in the energy balance. Nevertheless, the addition or subtraction of this amount in the energy balance equation should be considered for evapo-transpiration calculation. Penman-Monteith method suggests approximate estimates of soil heat flows as the difference between the maxima and minimum daily temperatures multiplied by a convenient coefficient. However, such approach ignores important variations in this parameter occurring during the day, and could influence the accuracy of the result. This work proposes to estimate soil heat flows by means of a mathematical model that includes the estimate of soil temperatures profiles and heat flows as a function of thermal properties of the soil, such as difussivity and conductivity coefficients. The model calculates soil heat flows in three stages. The first estimates hourly air temperature based on the average daily temperature and Fourier series coefficients. The obtained hourly air temperature constitutes an input variable for the second stage of the model. Surface soil temperature is assumed to be equal to air temperature. The second stage, applies heat transfer principles, using the thermal properties of the soil in order to obtain the soil temperature profile in a one meter depth soil stratum. Finally, the results of the second stage are used to calculate the hourly heat flow in the soil and compare this estimate with other methods and with measured values. Calculated hourly temperatures reproduced observed values closely. Correlation coefficients between observed and calculated values for the three summer months are 0.98, 0.96 and 0.97. Hourly soil heat fluxes are also closely estimated, showing

  3. Supply temperature control concepts in heat pump heating systems

    OpenAIRE

    Huchtemann, Kristian

    2015-01-01

    In recent years, electrically driven compression heat pumps have come to be widely used for the heating of buildings. Their efficiency strongly depends on the temperature lift which is influenced by the supply temperature of the heat sink. When used with radiator heating systems it is challenging to operate heat pumps efficiently because high supply temperatures are required. Therefore, in order to efficiently operate heat pumps, this work analyses advanced control concepts for heatpump heati...

  4. Optimal heat transport

    Science.gov (United States)

    Souza, Andre; Doering, Charles R.

    2015-11-01

    The transport of heat by buoyancy driven flows, i.e., thermal convection plays a central role in many natural phenomena and an understanding of how to control its mechanisms is relevant to many engineering applications. In this talk we will consider a variational formulation of optimal heat transport in simple geometries. Numerical results, limits on heat transport, and a comparison to Rayleigh-Bénard convection will be presented. Research supported by NSF Awards PHY-1205219, PHY-1338407, PHY-1443836, PHY-1533555 and DMS-1515161.

  5. Episodic coronal heating

    Science.gov (United States)

    Sturrock, P. A.; Dixon, W. W.; Klimchuk, J. A.; Antiochos, S. K.

    1990-01-01

    A study is made of the observational consequences of the hypothesis that there is no steady coronal heating, the solar corona instead being heated episodically, such that each short burst of heating is followed by a long period of radiative cooling. The form of the resulting contribution to the differential emission measure (DEM), and to a convenient related function (the differential energy flux, DEF) is calculated. Observational data for the quiet solar atmosphere indicate that the upper branch of the DEM, corresponding to temperatures above 100,000 K, can be interpreted in terms of episodic energy injection at coronal temperatures.

  6. Heat exchanger design handbook

    CERN Document Server

    Thulukkanam, Kuppan

    2013-01-01

    Completely revised and updated to reflect current advances in heat exchanger technology, Heat Exchanger Design Handbook, Second Edition includes enhanced figures and thermal effectiveness charts, tables, new chapter, and additional topics--all while keeping the qualities that made the first edition a centerpiece of information for practicing engineers, research, engineers, academicians, designers, and manufacturers involved in heat exchange between two or more fluids.See What's New in the Second Edition: Updated information on pressure vessel codes, manufacturer's association standards A new c

  7. Heat pump planning handbook

    CERN Document Server

    Bonin, Jürgen

    2015-01-01

    The Heat Pump Planning Handbook contains practical information and guidance on the design, planning and selection of heat pump systems, allowing engineers, designers, architects and construction specialists to compare a number of different systems and options. Including detailed descriptions of components and their functions and reflecting the current state of technology this guide contains sample tasks and solutions as well as new model calculations and planning evaluations. Also economic factors and alternative energy sources are covered, which are essential at a time of rising heat costs. T

  8. Waste heat recovery system

    International Nuclear Information System (INIS)

    Full text: The Konzen in-house designed anaerobic digester system for the POME (Palm Oil Mill Effluent) treatment process is one of the registered Clean Development Mechanism (CDM) projects in Malaysia. It is an organic wastewater treatment process which achieves excellent co-benefits objectives through the prevention of water pollution and reduction of greenhouse gas emissions, which is estimated to be 40,000 to 50,000 t-CO2 per year. The anaerobic digester was designed in mesophile mode with temperature ranging from 37 degree Celsius to 45 degree Celsius. A microorganisms growth is optimum under moderately warm temperature conditions. The operating temperature of the anaerobic digester needs to be maintained constantly. There are two waste heat recovery systems designed to make the treatment process self-sustaining. The heat recovered will be utilised as a clean energy source to heat up the anaerobic digester indirectly. The first design for the waste heat recovery system utilises heat generated from the flue gas of the biogas flaring system. A stainless steel water tank with an internal water layer is installed at the top level of the flare stack. The circulating water is heated by the methane enriched biogas combustion process. The second design utilizes heat generated during the compression process for the biogas compressor operation. The compressed biogas needs to be cooled before being recycled back into the digester tank for mixing purposes. Both the waste heat recovery systems use a design which applies a common water circulation loop and hot water tank to effectively become a closed loop. The hot water tank will perform both storage and temperature buffer functions. The hot water is then used to heat up recycled sludge from 30 degree Celsius to 45 degree Celsius with the maximum temperature setting at 50 degree Celsius. The recycled sludge line temperature will be measured and monitored by a temperature sensor and transmitter, which will activate the

  9. Episodic coronal heating

    International Nuclear Information System (INIS)

    A study is made of the observational consequences of the hypothesis that there is no steady coronal heating, the solar corona instead being heated episodically, such that each short burst of heating is followed by a long period of radiative cooling. The form of the resulting contribution to the differential emission measure (DEM), and to a convenient related function (the differential energy flux, DEF) is calculated. Observational data for the quiet solar atmosphere indicate that the upper branch of the DEM, corresponding to temperatures above 100,000 K, can be interpreted in terms of episodic energy injection at coronal temperatures. 22 refs

  10. Heat conduction in nanofluids

    Energy Technology Data Exchange (ETDEWEB)

    Wang Liqiu [Department of Mechanical Engineering, University of Hong Kong, Pokfulam Road (Hong Kong)], E-mail: lqwang@hkucc.hku.hk; Wei Xiaohao [Department of Mechanical Engineering, University of Hong Kong, Pokfulam Road (Hong Kong)

    2009-03-15

    We show that macroscale heat conduction in nanofluids is of a dual-phase-lagging type rather than the Fourier type. This leads to models for effective thermal capacity, conductivity and diffusivity of nanofluids and reveals even more anomalous thermal behavior of nanofluids than those reported in the literature. Due to the coupled conduction of the two phases, thermal waves and possibly resonance may appear in nanofluid heat conduction. Such waves and resonance are responsible for the extraordinary conductivity enhancement. The analysis and result are also valid for heat conduction in two-phase systems.

  11. Primary energy savings using heat storage for biomass heating systems

    OpenAIRE

    Mitrović Dejan M.; Janevski Jelena N.; Laković Mirjana S.

    2012-01-01

    District heating is an efficient way to provide heat to residential, tertiary and industrial users. The heat storage unit is an insulated water tank that absorbs surplus heat from the boiler. The stored heat in the heat storage unit makes it possible to heat even when the boiler is not working, thus increasing the heating efficiency. In order to save primary energy (fuel), the boiler operates on nominal load every time it is in operation (for the purpose of this research). The aim of th...

  12. Counterflow Regolith Heat Exchanger Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat...

  13. Heat Stress in Older Adults

    Science.gov (United States)

    ... Landslides Tornadoes Tsunamis Volcanoes Wildfires Winter Weather Heat Stress in Older Adults Recommend on Facebook Tweet Share ... What You Can Do for Someone With Heat Stress If you see any signs of severe heat ...

  14. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    As a consequence of global climate change, heat stress together with other abiotic stresses will remain an important determinant of future food security. Wheat (Triticum aestivum L.) is the third most important crop of the world feeding one third of the world population. Being a crop of temperate...... climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology and...... genetic determination (GD). An initial mass screening of 1,274 wheat cultivars (diverse origin) showed a GD of 8.5%. A stronger heat treatment was given in the second screening with 138 selected cultivars resulting in larger differentiation of cultivars (GD 15.4%). The GD further increased to 27.9% in the...

  15. Radiative heat transfer

    CERN Document Server

    Modest, Michael F

    2013-01-01

    The third edition of Radiative Heat Transfer describes the basic physics of radiation heat transfer. The book provides models, methodologies, and calculations essential in solving research problems in a variety of industries, including solar and nuclear energy, nanotechnology, biomedical, and environmental. Every chapter of Radiative Heat Transfer offers uncluttered nomenclature, numerous worked examples, and a large number of problems-many based on real world situations-making it ideal for classroom use as well as for self-study. The book's 24 chapters cover the four major areas in the field: surface properties; surface transport; properties of participating media; and transfer through participating media. Within each chapter, all analytical methods are developed in substantial detail, and a number of examples show how the developed relations may be applied to practical problems. It is an extensive solution manual for adopting instructors. Features: most complete text in the field of radiative heat transfer;...

  16. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... Care Fact Sheet Health & Safety Tips Campaigns SUBSCRIBE Emergencies A-Z Share this! Home » Emergency 101 Heat- ... CPR if the person becomes unconscious. READ IN EMERGENCIES A-Z Teeth (Dental Emergencies) Vomiting and Diarrhea ...

  17. Analytical heat transfer

    CERN Document Server

    Han, Je-Chin

    2012-01-01

    … it will complete my library … [and] complement the existing literature on heat transfer. It will be of value for both graduate students and faculty members.-Bengt Sunden, Lund University, Sweden

  18. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... pulse; rapid, shallow breathing; vomiting; and increased body temperature of more than 104 degrees. People with these ... loss of consciousness, vomiting or a high body temperature. For late stage heat stroke symptoms, cool the ...

  19. Heating of toroidal plasmas

    International Nuclear Information System (INIS)

    The limitations of ohmic heating in achieving the thermonuclear ignition of a low-β toroidal plasma can be overcome by using several heating methods. Such methods are: fast neutral beam injection (possibly combined with an adiabatic compression or any other means) and HF heating, the most interesting schemes being based on plasma resonances. The basic physical phenomena in each method are briefly explained and results obtained are given. A new heating scheme using an outer frequency of a few kHz is described, that makes it possible to locate the exciting coils outside the vacuum vessel (some of these coils can be that producing the vertical magnetic field for the plasma equilibrium)

  20. Policies for Renewable Heat

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    This paper builds on IEA publications, Deploying Renewables, Principles for Effective Policies and Deploying Renewables, Best and Future Policy Practice, that discuss the 'integrated policy approach,' whereby renewable energy technologies require different support policies at different stages of their maturity pathways. The paper discusses how the integrated policy approach applies to renewable heat. It attempts to provide guidance for policy-makers on renewable heat throughout the different phases of the policy lifecycle, allowing for the specific challenges of renewable heat and needs of the many stakeholders involved. Stimulating a market for heat involves challenges that are different and, often, more difficult to overcome than in the electricity and transport sectors.

  1. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... exhaustion symptoms include cool, moist, pale or flushed skin; headache; dizziness; weakness; feeling exhausted; heavy sweating; nausea; ... stage of heat illness) include flushed, hot, dry skin; fainting; a rapid, weak pulse; rapid, shallow breathing; ...

  2. Geodesics in Heat

    OpenAIRE

    Crane, Keenan; Weischedel, Clarisse; Wardetzky, Max

    2012-01-01

    We introduce the heat method for computing the shortest geodesic distance to a specified subset (e.g., point or curve) of a given domain. The heat method is robust, efficient, and simple to implement since it is based on solving a pair of standard linear elliptic problems. The method represents a significant breakthrough in the practical computation of distance on a wide variety of geometric domains, since the resulting linear systems can be prefactored once and subsequently solved in near-li...

  3. Heat Switches for ADRs

    Science.gov (United States)

    DiPirro, M. J.; Shirron, P. J.

    2014-01-01

    Heat switches are key elements in the cyclic operation of Adiabatic Demagnetization Refrigerators (ADRs). Several of the types of heat switches that have been used for ADRs are described in this paper. Key elements in selection and design of these switches include not only ON/OFF switching ratio, but also method of actuation, size, weight, and structural soundness. Some of the trade-off are detailed in this paper.

  4. Thermal radiation heat transfer

    CERN Document Server

    Howell, John R; Siegel, Robert

    2016-01-01

    Further expanding on the changes made to the fifth edition, Thermal Radiation Heat Transfer, 6th Edition continues to highlight the relevance of thermal radiative transfer and focus on concepts that develop the radiative transfer equation (RTE). The book explains the fundamentals of radiative transfer, introduces the energy and radiative transfer equations, covers a variety of approaches used to gauge radiative heat exchange between different surfaces and structures, and provides solution techniques for solving the RTE.

  5. Superradiant Quantum Heat Engine

    OpenAIRE

    Hardal, Ali Ü. C.; Müstecaplıoğlu, Özgür E.

    2015-01-01

    Scientific Reports | 5:12953 | DOI: 10.1038/srep12953 1 www.nature.com/scientificreports Superradiant Quantum Heat Engine Ali Ü. C. Hardal & Özgür E. Müstecaplıoğlu Quantum physics revolutionized classical disciplines of mechanics, statistical physics, and electrodynamics. One branch of scientific knowledge however seems untouched: thermodynamics. Major motivation behind thermodynamics is to develop eficient heat engines. Technology has a trend to miniaturize engines, ...

  6. Conducting the Heat

    Science.gov (United States)

    2003-01-01

    Heat conduction plays an important role in the efficiency and life span of electronic components. To keep electronic components running efficiently and at a proper temperature, thermal management systems transfer heat generated from the components to thermal surfaces such as heat sinks, heat pipes, radiators, or heat spreaders. Thermal surfaces absorb the heat from the electrical components and dissipate it into the environment, preventing overheating. To ensure the best contact between electrical components and thermal surfaces, thermal interface materials are applied. In addition to having high conductivity, ideal thermal interface materials should be compliant to conform to the components, increasing the surface contact. While many different types of interface materials exist for varying purposes, Energy Science Laboratories, Inc. (ESLI), of San Diego, California, proposed using carbon velvets as thermal interface materials for general aerospace and electronics applications. NASA s Johnson Space Center granted ESLI a Small Business Innovation Research (SBIR) contract to develop thermal interface materials that are lightweight and compliant, and demonstrate high thermal conductance even for nonflat surfaces. Through Phase II SBIR work, ESLI created Vel-Therm for the commercial market. Vel-Therm is a soft, carbon fiber velvet consisting of numerous high thermal conductivity carbon fibers anchored in a thin layer of adhesive. The velvets are fabricated by precision cutting continuous carbon fiber tows and electrostatically flocking the fibers into uncured adhesive, using proprietary techniques.

  7. Optimal design of the separate type heat pipe heat exchanger

    Institute of Scientific and Technical Information of China (English)

    YU Zi-tao; HU Ya-cai; CEN Ke-fa

    2005-01-01

    Separate type heat pipe heat exchangers are often used for large-scale heat exchanging. The arrangement of such a heat exchanger conveniently allows heat input to and output from the heat exchanger at remote locations. The traditional method of designing an ordinary HPHE (heat pipe heat exchanger) is commonly applied in the separate type exchanger design, but the calculations have to be carried out separately, which makes it very complicated. In this work, the ε-NTU (effectiveness-Number of Transfer Units) method was applied for optimization analysis of single- or multi-level separate type heat pipe heat exchangers. An optimizing formula for single-level separate type heat pipe heat exchangers was obtained. The optimizing principles of effectiveness-NTU and heat transfer rate by the equal distribution method for multi-level separate type heat pipe heat exchanger are presented. The design of separate type heat pipe heat exchangers by the optimizing method is more convenient and faster than by the traditional method.

  8. HEAT EXCHANGERS IN SEWAGE PIPES

    OpenAIRE

    Podobeková, Veronika; Peráčková, Jana

    2014-01-01

    The article discusses utilization of heat from waste water in sewage. During the year, temperature of water in sewage ranges between 10 °C and 20 °C and the heat from sewage could be used for heating, cooling and hot water preparation in building. The heat is extracted through a transfer surface area of the heat exchanger into the heat pump, which is able to utilize the low–potential energy. Different design and types of the heat exchangers in sewage are dealt with: heat exchangers embedded i...

  9. VII international district heating conference

    International Nuclear Information System (INIS)

    The proceedings of the 7th International District Heating Conference contain the full texts of the 89 presented papers of which 11 fall under the INIS Subject Scope. The conference met in seven sessions and dealt with the following problem areas: design and optimization of systems of district heating, integration of the power system and the district heating systems, cooperation of nuclear and fossil burning sources in district heating systems, the use of specific nuclear power plants for heating purposes, questions of the control of systems of district heating, the development of components of heating networks, the reliability and design of heat supply pipes. (Z.M.)

  10. Utilization of heat pipes for transfer heat from the flue gas into the heat transfer medium

    Directory of Open Access Journals (Sweden)

    Lenhard Richard

    2014-03-01

    Full Text Available The contribution is listed possible application of heat pipes in systems for obtaining heat from flue gas of small heat sources. It is also stated in the contribution design an experimental device on which to study the impact of fill (the quantity, type of load at various temperature parameters (temperature heating and cooling thermal power transferred to the heat pipe. Is listed measurement methodology using heat pipes designed experimental facility, measurement results and analysis of the results obtained.

  11. Numerical research of heat transfer in gas heat exchanger

    OpenAIRE

    Khomutov Eugene O.; Gil Andrey V.

    2015-01-01

    The article presents a numerical study of heat and mass transfer based on the finite volume method. Researched by installing a tubular heat exchanger for heating of natural gas. The results according to changes in temperature of the natural gas depend on the initial temperature of the heating flow. The results can be used in the analysis of further effective combustion.

  12. Heat exchanger device and method for heat removal or transfer

    Science.gov (United States)

    Koplow, Jeffrey P

    2013-12-10

    Systems and methods for a forced-convection heat exchanger are provided. In one embodiment, heat is transferred to or from a thermal load in thermal contact with a heat conducting structure, across a narrow air gap, to a rotating heat transfer structure immersed in a surrounding medium such as air.

  13. Heat Pump with Two Heat Sources on Different Temperature Levels

    OpenAIRE

    Bertsch, Stefan; Uhlmann, Michael; Heldstab, Andres

    2014-01-01

    Aim of the project is the development of a new heat pump system with economizing that is able to improve the heating performance using two or more different heat sources. These heat sources preferably on different temperature levels are incorporated in the system with minimal loss of exergy, by adding the heat at different pressure levels. Applications are i.e. buildings with heat pump and a solar thermal collector. While solar thermal systems can be used for heating and domestic hot water in...

  14. Heat exchanger restart evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, J.M.; Hirst, C.W.; Lentz, T.F.

    1992-03-18

    On December 24, 1991, the K-Reactor was in the shutdown mode with full AC process water flow and full cooling water flow. Safety rod testing was being performed as part of the power ascension testing program. The results of cooling water samples indicated tritium concentrations higher than allowable. Further sampling and testing confirmed a Process Water System to Cooling Water System leak in heat exchanger 4A (HX 4A). The heat exchanger was isolated and the plant shutdown. Heat exchanger 4A was removed from the plant and moved to C-Area prior to performing examinations and diagnostic testing. This included locating and identifying the leaking tube or tubes, eddy current examination of the leaking tube and a number of adjacent tubes, visually inspecting the leaking tube from both the inside as well as the area surrounding the identified tube. The leaking tube was removed and examined metallurgically to determine the failure mechanism. In addition ten other tubes that either exhibited eddy current indications or would represent a baseline condition were removed from heat exchanger 4A for metallurgical examination. Additional analysis and review of heat exchanger leakage history was performed to determine if there are any patterns which can be used for predictive purposes. Compensatory actions have been taken to improve the sensitivity and response time to any future events of this type. The results of these actions are summary herein.

  15. Heat exchanger restart evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, J.M.; Hirst, C.W.; Lentz, T.F.

    1992-03-18

    On December 24, 1991, the K-Reactor was in the shutdown mode with full AC process water flow and full cooling water flow. Safety rod testing was being performed as part of the power ascension testing program. The results of cooling water samples indicated tritium concentrations higher than allowable. Further sampling and testing confirmed a Process Water System to Cooling Water System leak in heat exchanger 4A (HX 4A). The heat exchanger was isolated and the plant shutdown. Heat exchanger 4A was removed from the plant and moved to C-Area prior to performing examinations and diagnostic testing. This included locating and identifying the leaking tube or tubes, eddy current examination of the leaking tube and a number of adjacent tubes, visually inspecting the leaking tube from both the inside as well as the area surrounding the identified tube. The leaking tube was removed and examined metallurgically to determine the failure mechanism. In addition ten other tubes that either exhibited eddy current indications or would represent a baseline condition were removed from heat exchanger 4A for metallurgical examination. Additional analysis and review of heat exchanger leakage history was performed to determine if there are any patterns which can be used for predictive purposes. Compensatory actions have been taken to improve the sensitivity and response time to any future events of this type. The results of these actions are summarized.

  16. Heat exchanger restart evaluation

    International Nuclear Information System (INIS)

    On December 24, 1991, the K-Reactor was in the shutdown mode with full AC process water flow and full cooling water flow. Safety rod testing was being performed as part of the power ascension testing program. The results of cooling water samples indicated tritium concentrations higher than allowable. Further sampling and testing confirmed a Process Water System to Cooling Water System leak in heat exchanger 4A (HX 4A). The heat exchanger was isolated and the plant shutdown. Heat exchanger 4A was removed from the plant and moved to C-Area prior to performing examinations and diagnostic testing. This included locating and identifying the leaking tube or tubes, eddy current examination of the leaking tube and a number of adjacent tubes, visually inspecting the leaking tube from both the inside as well as the area surrounding the identified tube. The leaking tube was removed and examined metallurgically to determine the failure mechanism. In addition ten other tubes that either exhibited eddy current indications or would represent a baseline condition were removed from heat exchanger 4A for metallurgical examination. Additional analysis and review of heat exchanger leakage history was performed to determine if there are any patterns which can be used for predictive purposes. Compensatory actions have been taken to improve the sensitivity and response time to any future events of this type. The results of these actions are summarized

  17. Heat Conduction in Lenses

    Directory of Open Access Journals (Sweden)

    Beat Aebischer

    2007-04-01

    Full Text Available We consider several heat conduction problems for glass lenses with different boundary conditions. The problems dealt with in Sections sec:1 to sec:3 are motivated by the problem of an airborne digital camera that is initially too cold and must be heated up to reach the required image quality. The problem is how to distribute the heat to the different lenses in the system in order to reach acceptable operating conditions as quickly as possible. The problem of Section sec:4 concerns a space borne laser altimeter for planetary exploration. Will a coating used to absorb unwanted parts of the solar spectrum lead to unacceptable heating? In this paper, we present analytic solutions for idealized cases that help in understanding the essence of the problems qualitatively and quantitatively, without having to resort to finite element computations. The use of dimensionless quantities greatly simplifies the picture by reducing the number of relevant parameters. The methods used are classical: elementary real analysis and special functions. However, the boundary conditions dictated by our applications are not usually considered in classical works on the heat equation, so that the analytic solutions given here seem to be new. We will also show how energy conservation leads to interesting sum formulae in connection with Bessel functions. The other side of the story, to determine the deterioration of image quality by given (inhomogeneous temperature distributions in the optical system, is not dealt with here.

  18. Ground Source Heat Pump in Heating System with Electronics Monitoring

    Directory of Open Access Journals (Sweden)

    NEAMŢU Ovidiu

    2013-10-01

    Full Text Available The monitoring system is implemented for a ground coupled heat pump in heating/ system. The borehole heat exchangers – which are 150 m long - are filled with a mixture of water and ethilene glycol calledbrine. Metering and monitoring energy consumption is achieved for: heat pump, circulation pumps, additional electrical heating, hot air ventilation systems, control systems with sensors: analog and smart sensors. Instantaneous values are stored in a local computer.

  19. Optimum geometry of MEMS heat exchanger for heat transfer enhancement

    OpenAIRE

    Nusrat J. Chhanda; Muhannad Mustafa; Maglub Al Nur

    2010-01-01

    The study is based on an analysis of MEMS heat exchanger of three different geometries: wavy, triangular and rectangular using water as test fluid. The problem is solved using finite element method. The aim of this analysis is to evaluate the performance of MEMS heat exchanger for different geometry and to obtain an optimum design for better heat enhancement. It is apparent from this work that rectangular surface heat exchanger shows the best performance for heat enhancement technique in comp...

  20. Optimization of heat exchanger for indirectly heated water heater

    OpenAIRE

    Kaduchová Katarína; Lenhard Richard; Jandačka Jozef

    2012-01-01

    Due to the optimization of geometrical parameters of the heat exchanger in indirect heated water heaters created a mathematical model of heating hot water, by which I have subsequently made the simulation of the device to change its geometrical parameters. Based on these results, the impacts of the geometrical parameters affect the performance of the heat exchanger. The results of the optimization to create a CFD model which watched at the behavior of optimized heat exchanger for indirect hea...

  1. Fault-Tolerant Heat Exchanger

    Science.gov (United States)

    Izenson, Michael G.; Crowley, Christopher J.

    2005-01-01

    A compact, lightweight heat exchanger has been designed to be fault-tolerant in the sense that a single-point leak would not cause mixing of heat-transfer fluids. This particular heat exchanger is intended to be part of the temperature-regulation system for habitable modules of the International Space Station and to function with water and ammonia as the heat-transfer fluids. The basic fault-tolerant design is adaptable to other heat-transfer fluids and heat exchangers for applications in which mixing of heat-transfer fluids would pose toxic, explosive, or other hazards: Examples could include fuel/air heat exchangers for thermal management on aircraft, process heat exchangers in the cryogenic industry, and heat exchangers used in chemical processing. The reason this heat exchanger can tolerate a single-point leak is that the heat-transfer fluids are everywhere separated by a vented volume and at least two seals. The combination of fault tolerance, compactness, and light weight is implemented in a unique heat-exchanger core configuration: Each fluid passage is entirely surrounded by a vented region bridged by solid structures through which heat is conducted between the fluids. Precise, proprietary fabrication techniques make it possible to manufacture the vented regions and heat-conducting structures with very small dimensions to obtain a very large coefficient of heat transfer between the two fluids. A large heat-transfer coefficient favors compact design by making it possible to use a relatively small core for a given heat-transfer rate. Calculations and experiments have shown that in most respects, the fault-tolerant heat exchanger can be expected to equal or exceed the performance of the non-fault-tolerant heat exchanger that it is intended to supplant (see table). The only significant disadvantages are a slight weight penalty and a small decrease in the mass-specific heat transfer.

  2. Heat Pipe Blocks Return Flow

    Science.gov (United States)

    Eninger, J. E.

    1982-01-01

    Metal-foil reed valve in conventional slab-wick heat pipe limits heat flow to one direction only. With sink warmer than source, reed is forced closed and fluid returns to source side through annular transfer wick. When this occurs, wick slab on sink side of valve dries out and heat pipe ceases to conduct heat.

  3. Fluctuation Relation for Heat Engines

    OpenAIRE

    Sinitsyn, N. A.

    2011-01-01

    We derive the exact equality, referred to as the fluctuation relation for heat engines (FRHE), that relates statistics of heat extracted from one of the two heat baths and the work per one cycle of a heat engine operation. Carnot's inequality of classical thermodynamics follows as a direct consequence of the FRHE.

  4. Determination of plasma heat conductivity

    International Nuclear Information System (INIS)

    The problem of determination of plasma electron heat conductivity is considered. The similar approach can be used to determine the coefficients of ion heat conductivity or diffusion. Generally it can be used to find the coefficient of heat conductivity (diffusion) in all the cases, where the concept of a continuous medium and a heat transfer model can be applied

  5. Structures to radiate heat softly

    Energy Technology Data Exchange (ETDEWEB)

    Perilae, T.; Wikstroem, T. [ed.

    1997-11-01

    Over the past fifty years, heating systems in single-family houses have taken a great leap forward. First wood-burning stoves gave way to oil heaters; then these were superseded by central heating systems; and now conventional central heating systems have lost their way with the increasingly widespread use of room-specific heating systems

  6. Experiments Demonstrate Geothermal Heating Process

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    When engineers design heat-pump-based geothermal heating systems for homes and other buildings, they can use coil loops buried around the perimeter of the structure to gather low-grade heat from the earth. As an alternative approach, they can drill well casings and store the summer's heat deep in the earth, then bring it back in the winter to warm…

  7. Performance of heat pumps with direct expansion in vertical ground heat exchangers in heating mode

    International Nuclear Information System (INIS)

    Highlights: • The work focuses on direct expansion ground source heat pumps in heating mode. • The evaporating process of the refrigerant fluid into boreholes is analyzed. • A method to design the direct expansion borehole heat exchangers is presented. • Direct expansion and the common secondary loop heat pumps are compared. • The comparison is carried out in terms of both borehole length and performance. - Abstract: Ground source heat pump systems represent an interesting example of renewable energy technology for heating and cooling of buildings. The connection with the ground is usually done by means of a closed loop where a heat-carrier fluid (pure water or a solution of antifreeze and water) flows and, in heating mode, moves heat from ground to refrigerant fluid of heat pump. A new solution is the direct expansion heat pump. In this case, the heat-carrier fluid inside the ground loop is the same refrigerant fluid of heat pump. This paper focuses on the energy performance of direct expansion ground source heat pump with borehole heat exchangers in heating mode, looking at residential building installations. For this purpose, the evaporating process of the refrigerant fluid inside vertical tubes is investigated in order to analyze the influence of the convective heat transfer coefficient on the global heat transfer with the surrounding ground. Then, an analytical model reported in literature for the design of common borehole heat exchangers has been modified for direct expansion systems. Finally, the direct expansion and common ground source heat pumps have been compared in terms of both total borehole length and thermal performance. Results indicate that the direct expansion system has higher energy performance and requires lower total borehole length compared to the common system. However, when the two systems are compared with the same mean fluid evaporating temperature, the overall length of the ground heat exchanger of the direct expansion heat

  8. District heating in Flensburg

    Energy Technology Data Exchange (ETDEWEB)

    Prinz, W.

    1981-01-01

    The majority of our population, but also of our authorities, are still skeptical or even disapproving towards district heating. The reasons of this negative attitude are partly psychological - e.g. the individualism of the Swiss and their dislike for too centralised structures and ''forced connections'' - but also the existence of finished gas supply networks and the fear of considerable pre-investments and torn streets over years. The following article - held as a speech on the information meeting ''District heating and the possible contribution of nuclear energy'' organised by the Swiss Association for Atomic Energy in Bern shows a practical problem solving at the example of the district heating in Flensburg and deals with these questions.

  9. Ventilation with heat recovery

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Svendsen, Svend

    2005-01-01

    This paper presents the experiences from the use of ventilation with heat recovery in several experimental single-family houses developed and built within the last four years to meet the new Danish energy requirements of 2005. Included are descriptions of the ventilation system components...... and the main functional demands as well as measurements of the thermal efficiency, electricity consumptions and building air tightness. The paper addresses the aspects of minimizing the heat loss from the duct system and the heat recovery unit (when placed in an unheated attic space) in order to obtain...... an acceptable efficiency. Furthermore, solutions to secure the air tightness of the building envelope are suggested. The paper does not address problems with condensate of water in the exchanger that may freeze in cold climate conditions. This complex of problem is dealt with in a separate paper....

  10. Elements of heat transfer

    CERN Document Server

    Rathakrishnan, Ethirajan

    2012-01-01

    1 Basic Concepts and Definitions1.1 Introduction1.1.1 Driving Potential1.2 Dimensions and Units1.2.1 Dimensional Homogeneity1.3 Closed and Open Systems1.3.1 Closed System (ControlMass)1.3.2 Isolated System1.3.3 Open System (ControlVolume)1.4 Forms of Energy1.4.1 Internal Energy1.5 Properties of a System1.5.1 Intensive and Extensive Properties1.6 State and Equilibrium1.7 Thermal and Calorical Properties1.7.1 Specific Heat of an Incompressible Substance1.7.2 Thermally Perfect Gas 1.8 The Perfect Gas1.9 Summary1.10 Exercise ProblemsConduction Heat Transfer2.1 Introduction2.2 Conduction Heat Trans

  11. Heat and mass transfer

    CERN Document Server

    Baehr, Hans Dieter

    2011-01-01

    This comprehensive textbook provides a solid foundation of knowledge on the principles of heat and mass transfer and shows how to solve problems by applying modern methods. The basic theory is developed systematically, exploring in detail the solution methods to all important problems.   The thoroughly revised 3rd edition includes an introduction to the numerical solution of Finite Elements. A new section on heat and mass transfer in porous media has also been added.   The book will be useful not only to upper-level and graduate students, but also to practicing scientists and engineers, offering a firm understanding of the principles of heat and mass transfer, and showing how to solve problems by applying modern methods. Many completed examples and numerous exercises with solutions facilitate learning and understanding, and an appendix includes data on key properties of important substances.

  12. Microgravity condensing heat exchanger

    Science.gov (United States)

    Thomas, Christopher M. (Inventor); Ma, Yonghui (Inventor); North, Andrew (Inventor); Weislogel, Mark M. (Inventor)

    2011-01-01

    A heat exchanger having a plurality of heat exchanging aluminum fins with hydrophilic condensing surfaces which are stacked and clamped between two cold plates. The cold plates are aligned radially along a plane extending through the axis of a cylindrical duct and hold the stacked and clamped portions of the heat exchanging fins along the axis of the cylindrical duct. The fins extend outwardly from the clamped portions along approximately radial planes. The spacing between fins is symmetric about the cold plates, and are somewhat more closely spaced as the angle they make with the cold plates approaches 90.degree.. Passageways extend through the fins between vertex spaces which provide capillary storage and communicate with passageways formed in the stacked and clamped portions of the fins, which communicate with water drains connected to a pump externally to the duct. Water with no entrained air is drawn from the capillary spaces.

  13. Large Scale Solar Heating

    DEFF Research Database (Denmark)

    Heller, Alfred

    2001-01-01

    The main objective of the research was to evaluate large-scale solar heating connected to district heating (CSDHP), to build up a simulation tool and to demonstrate the application of the simulation tool for design studies and on a local energy planning case. The evaluation was mainly carried out...... model is designed and validated on the Marstal case. Applying the Danish Reference Year, a design tool is presented. The simulation tool is used for proposals for application of alternative designs, including high-performance solar collector types (trough solar collectors, vaccum pipe collectors......). Simulation programs are proposed as control supporting tool for daily operation and performance prediction of central solar heating plants. Finaly the CSHP technolgy is put into persepctive with respect to alternatives and a short discussion on the barries and breakthrough of the technology are given....

  14. Thermal radiation heat transfer

    CERN Document Server

    Howell, John R; Mengüç, M Pinar

    2011-01-01

    Providing a comprehensive overview of the radiative behavior and properties of materials, the fifth edition of this classic textbook describes the physics of radiative heat transfer, development of relevant analysis methods, and associated mathematical and numerical techniques. Retaining the salient features and fundamental coverage that have made it popular, Thermal Radiation Heat Transfer, Fifth Edition has been carefully streamlined to omit superfluous material, yet enhanced to update information with extensive references. Includes four new chapters on Inverse Methods, Electromagnetic Theory, Scattering and Absorption by Particles, and Near-Field Radiative Transfer Keeping pace with significant developments, this book begins by addressing the radiative properties of blackbody and opaque materials, and how they are predicted using electromagnetic theory and obtained through measurements. It discusses radiative exchange in enclosures without any radiating medium between the surfaces-and where heat conduction...

  15. Heat transfer fluids containing nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Dileep; Routbort, Jules; Routbort, A.J.; Yu, Wenhua; Timofeeva, Elena; Smith, David S.; France, David M.

    2016-05-17

    A nanofluid of a base heat transfer fluid and a plurality of ceramic nanoparticles suspended throughout the base heat transfer fluid applicable to commercial and industrial heat transfer applications. The nanofluid is stable, non-reactive and exhibits enhanced heat transfer properties relative to the base heat transfer fluid, with only minimal increases in pumping power required relative to the base heat transfer fluid. In a particular embodiment, the plurality of ceramic nanoparticles comprise silicon carbide and the base heat transfer fluid comprises water and water and ethylene glycol mixtures.

  16. Intensification of Convective Heat Transfer in Heating Device of Mobile Heating System with BH-Heat Generator

    Directory of Open Access Journals (Sweden)

    N. Nesenchuk

    2013-01-01

    Full Text Available Directions pertaining to intensification of convective heat transfer in a soft heating device have been experimentally investigated  in the paper and the most efficient one has been selected that is creation of artificial roughness on the device surface. The considered heating device for a heat supply system of a mobile object has been made of soft polymer material (polyvinyl chloride. Following  evaluation results of  heat exchange intensification a criteria equation has been obtained for calculation of external heat transfer with due account of heat transfer intensification.

  17. Heat transfer studies

    International Nuclear Information System (INIS)

    Drying in subresidually-saturated systems at elevated temperatures has been studied for two different operating conditions. One condition started with flowing nitrogen gas through the test section and simultaneously heating up the porous medium at the same time (denoted in what follows as the ''transient heating case''). The other condition started initially with heating up the porous medium with no flow, and then running the nitrogen gas flow through the test section after a steady-state temperature distribution had been reached (denoted in what follows as the ''steady heating case''). A 90 degrees C isothermal boundary condition was set on the aluminum wall. An average of 9% discrepancy in the mass balance calculation compared to the digital balance measurement has been found in the transient heating case. An average of 4.3% discrepancy in the mass balance calculation compared to the digital balance measurement has been found after the nitrogen gas flowed through test section for the steady heating case. A large discrepancy has also been found before the nitrogen gas admitted to the test section. This is because some of subresidual water in the test section has been drained out from the bottom due to the gravity effect and the strong convection flow in the porous medium before the nitrogen gas is admitted. This discrepancy may be reduced by closing the end tube at bottom before the nitrogen gas is admitted to the test section. The drying characteristics of this system are reported. A theoretical study has also been initiated in an attempt to supplement the experimental results, and this system is described in the report. A one-dimensional transient system is assumed in which a two-component (condensable and noncondensable) gas mixture flows through a porous medium with evaporation. The numerical calculation will be performed in the future work to compare to the experimental results

  18. Ceramic heat recuperators for industrial heat recovery

    Science.gov (United States)

    Cleveland, J. J.; Gonzalez, J. M.; Kohnken, K. H.; Rebello, W. J.

    1980-08-01

    A cordierite (magnesium aluminum silicate) recuperator was designed for relatively small furnaces with firing rates of 0.3 MM to 0.6 MM Btu/h and with exhaust gas temperatures of 1500 F to 2600 F. Five demonstration programs were performed to determine the heat transfer performance of the device, establish the energy savings by recovery, demonstrate the durability of the ceramic core, determine the operating requirements of the burners and controls with recuperation, and establish the overall system costs and payback period. The recuperator is described and results of tests and measurements, system economics, and cost performance analyses are presented. The methodology is developed and techniques for impact analysis are described. Industrial applications are implied and a process flow diagram for smelting and refining primary copper is shown.

  19. Convective Heat Transfer

    CERN Document Server

    Favre-Marinet, Michel

    2009-01-01

    Convection heat transfer is an important topic both for industrial applications and fundamental aspects. It combines the complexity of the flow dynamics and of the active or passive scalar transport process. It is part of many university courses such as Mechanical, Aeronautical, Chemical and Biomechanical Engineering. The literature on convective heat transfer is large, but the present manuscript differs in many aspects from the existing ones, particularly from the pedagogical point of view. Each chapter begins with a brief yet complete presentation of the related topic. This is followed by a

  20. A heat transfer textbook

    CERN Document Server

    Lienhard, John H

    2011-01-01

    This introduction to heat transfer offers advanced undergraduate and graduate engineering students a solid foundation in the subjects of conduction, convection, radiation, and phase-change, in addition to the related topic of mass transfer. A staple of engineering courses around the world for more than three decades, it has been revised and updated regularly by the authors, a pair of recognized experts in the field. The text addresses the implications, limitations, and meanings of many aspects of heat transfer, connecting the subject to its real-world applications and developing students' ins

  1. Solar industrial process heat

    Energy Technology Data Exchange (ETDEWEB)

    Lumsdaine, E.

    1981-04-01

    The aim of the assessment reported is to candidly examine the contribution that solar industrial process heat (SIPH) is realistically able to make in the near and long-term energy futures of the United States. The performance history of government and privately funded SIPH demonstration programs, 15 of which are briefly summarized, and the present status of SIPH technology are discussed. The technical and performance characteristics of solar industrial process heat plants and equipment are reviewed, as well as evaluating how the operating experience of over a dozen SIPH demonstration projects is influencing institutional acceptance and economoc projections. Implications for domestic energy policy and international implications are briefly discussed. (LEW)

  2. [Pathophysiology of heat illness].

    Science.gov (United States)

    Aruga, Tohru; Miyake, Yasufumi

    2012-06-01

    Human core temperature is strictly controlled by mechanism of radiation, conduction, convection, and evaporation from skin surface. Serial hot and humid climate induces dehydration which interferes heat pump-out from the body. Heart dysfunction is the third factor to rise body temperature. Hyperthermia and hypo-perfusion caused by dehydration and heart failure deteriorate specific organ functions, i.e. central nervous system, liver and renal functions and coagulation system. Disseminated intravascular coagulopathy is one of the standard indicators of severity and mortality of heat stroke. PMID:22690597

  3. Adaptive heat engine

    OpenAIRE

    Allahverdyan, A.E.; Babajanyan, S. G.; Martirosyan, N. H.; Melkikh, A. V.

    2016-01-01

    A major limitations for many heat engines is that their functioning demands on-line control, and/or an external fitting between environmental parameters (e.g. temperatures of thermal baths) and internal parameters of the engine. We study a model for an adaptive heat engine, where---due to feedback from the functional part---the engine's structure adapts to given thermal baths. Hence no on-line control and no external fitting are needed. The engine can employ unknown resources, it can also ada...

  4. Harnessing solar heat

    CERN Document Server

    Norton, Brian

    2013-01-01

    Systems engineered by man to harness solar heat in a controlled manner now include a diverse range of technologies each serving distinctive needs in particular climate contexts. This text covers the breadth of solar energy technologies for the conversion of solar energy to provide heat, either as the directly-used output or as an intermediary to other uses such as power generation or cooling. It is a wholly updated, extended and revised version of “Solar Energy Thermal Technology” first published in 1992. The text draws on the own author’s research and that of numerous colleagues and

  5. Alfven wave heating

    International Nuclear Information System (INIS)

    The physics of Alfven-wave heating is particularly sensitive to the character of the linear mode conversion which occurs at the Alfven resonance layer. Parameter changes can profoundly affect both the location within the plasma and the mechanism for the power absorption. Under optimal conditions the heating power may be absorbed by electron Landau damping and by electron transit-time magnetic pumping in the plasma interior, or by the same processes acting near the resonance layer on the mode-converted kinetic Alfven wave. The method is outlined for computing the coefficients for reflection, transmission and absorption at the resonance layer and some representative results are offered

  6. Heat exchanger panel

    Science.gov (United States)

    Warburton, Robert E. (Inventor); Cuva, William J. (Inventor)

    2005-01-01

    The present invention relates to a heat exchanger panel which has broad utility in high temperature environments. The heat exchanger panel has a first panel, a second panel, and at least one fluid containment device positioned intermediate the first and second panels. At least one of the first panel and the second panel have at least one feature on an interior surface to accommodate the at least one fluid containment device. In a preferred embodiment, each of the first and second panels is formed from a high conductivity, high temperature composite material. Also, in a preferred embodiment, the first and second panels are joined together by one or more composite fasteners.

  7. Geothermal heating saves energy

    International Nuclear Information System (INIS)

    The article reviews briefly a pioneer project for a construction area of 200000 m''2 with residences, business complexes, a hotel and conference centre and a commercial college in Oslo. The energy conservation potential is estimated to be about 60-70 % compared to direct heating with oil, gas or electricity as sources. There will also be substantial reduction in environmentally damaging emissions. The proposed energy central combines geothermal energy sources with heat pump technology, utilises water as energy carrier and uses terrestrial wells for energy storage. A cost approximation is presented

  8. Heat exposure effects among firefighters

    OpenAIRE

    Patel Harshad; Rao Nellore; Saha Asim

    2006-01-01

    Background: Firefighting is a hazardous occupation. The firefighters (FF) in extinguishing fire are often exposed to extreme heat of 1200oC to 1400oC temperature. The heat exposure effects may occur from hot air, radiant heat, contact with hot surfaces, endogenous heat produced by the body during exercise, which cannot be cooled during fire. A significant morbidity and mortality from exposure to heat was reported in other countries but not from India. Aims : Present study focuses on prevale...

  9. HEAT ACCUMULATION IN HELIUM GROUND SYSTEMS IN HEAT PUMP SUPPLY

    Directory of Open Access Journals (Sweden)

    A. I. Kolosov

    2012-04-01

    Full Text Available Problem statement. The paper discusses the problem of estimation of prospects of heat accumulation in the combined systems of heat supply with the use of low potential energy of renewable sources (sun and ground and heat pumps for increase of their potential.Results and conclusions. The use of heat accumulators in combined heating systems that utilize low-potential solar and ground energy as primary energy sources and heat pumps to boost the po-tential of the latter was discussed. A method of calculating ground heat exchangers that use the heat pump cycle to increase a thermal potential of renewable energy sources was set forth. An at-tempt was made at addressing the problem of heat and mass transfer in ground when ground ac-cumulators like “a Field’s tube” are used: a geothermal circulation system comprises two wells (pumping and operational.

  10. Spatial Heat Planning and Heat Demand Reductions in Buildings

    DEFF Research Database (Denmark)

    Nielsen, Steffen; Møller, Bernd; Lund, Henrik

    2013-01-01

    long-term savings in investments in production capacity and fuel costs. Through a case study, the amount of these long-term sav-ings is compared to the costs of implementing heat savings. The case study shows that heat reductions of roughly 50% are feasible if the long-term costs are included. Savings...... on the heat supply in Denmark. Even though the focus is on Denmark, the methods and results are applicable to other places as well, as they build on assumptions that are also present in other countries. In Denmark approximately half of the heat demand is sup-plied by district heating, and half of the district...... heating already uses renew-able energy. Within densely built-up areas district heating systems are re-source effective compared to individual solutions as district heating sys-tems can use excess heat from power plants, industries, and waste incin-eration as well as renewable energy, like geothermal...

  11. Primary energy savings using heat storage for biomass heating systems

    Directory of Open Access Journals (Sweden)

    Mitrović Dejan M.

    2012-01-01

    Full Text Available District heating is an efficient way to provide heat to residential, tertiary and industrial users. The heat storage unit is an insulated water tank that absorbs surplus heat from the boiler. The stored heat in the heat storage unit makes it possible to heat even when the boiler is not working, thus increasing the heating efficiency. In order to save primary energy (fuel, the boiler operates on nominal load every time it is in operation (for the purpose of this research. The aim of this paper is to analyze the water temperature variation in the heat storage, depending on the heat load and the heat storage volume. Heat load is calculated for three reference days, with average daily temperatures from -5 to 5°C. The primary energy savings are also calculated for those days in the case of using heat storage in district heating.[Projekat Ministarstva nauke Republike Srbije, br. TR 33051: The concept of sustainable energy supply of settlements with energy efficient buildings

  12. Waste heat of HTR power stations for district heating

    International Nuclear Information System (INIS)

    The market situation, the applied techniques, and the transport, for district heating in combination with HTR plants are considered. Analysis of the heat market indicates a high demand for heat at temperatures between 100 and 1500C in household and industry. This market for district heating can be supplied by heat generated in HTR plants using two methods: (1) the combined heat and power generation in steam cycle plants by extracting steam from the turbine, and (2) the use of waste heat of a closed gas turbine cycle. The heat generation costs of (2) are negligible. The cost for transportation of heat over the average distance between existing plant sites and consumer regions (25 km) are between 10 and 20% of the total heat price, considering the high heat output of nuclear power stations. Comparing the price of heat gained by use of waste heat in HTR plants with that of conventional methods, considerable advantages are indicated for the combined heat and power generation in HTR plants. (author)

  13. Flow boiling heat transfer in volumetrically heated packed bed

    International Nuclear Information System (INIS)

    Highlights: • The onset of nucleate boiling in the volumetrically heated packed bed is researched. • A correlation for predicting qONB is developed. • The effects on boiling heat transfer coefficient are investigated. - Abstract: The volumetrically heated packed bed has been widely utilized in modern industry. However, due to the variability and randomness of packed bed channels, flow boiling heat transfer characteristics becomes complex, and there are no published research regarding this topic. To study flow boiling heat transfer characteristics of volumetrically heated packed beds, electromagnetic induction heating method is used to heat oxidized carbon steel balls adopted to stack the packed bed, with water as coolant in the experiment. The experimental results indicate that heat flux at onset of nucleate boiling (ONB) increases as mass flux and inlet subcooling are increased. A new correlation is developed to predict the ONB heat flux qONB in volumetrically heated packed bed, the predictions by which agree well with the experimental data, and the deviation remains less than 15%. Subcooled flow boiling heat transfer coefficient (hsub) increases with increasing mass flux, and equilibrium quality is slightly affected by heat flux. The saturated flow boiling heat transfer coefficient (hsat) increases with mass flux and equilibrium quality when equilibrium quality is lower than about 0.05, while the nucleate boiling is suppressed when the equilibrium quality exceeds a certain value

  14. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L; Kehlet, H

    2000-01-01

    before heat injury (47 degrees C, 7 min) and naloxone infiltration s.c. (0.2 mg) 2.5 h after the heat injury. Hyperalgesia to mechanical and heat stimuli were examined using von Frey hairs and thermodes, and pain was rated using a visual analogue scale. The burns produced significant hyperalgesia, but...

  15. Heat Transfer Characteristics of SiC-coated Heat Pipe for Passive Decay Heat Removal

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Mo; Kim, In Guk; Jeong, Yeong Shin; Bang, In Cheol [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)

    2014-10-15

    The main concern with the Fukushima accident was the failure of active and passive core cooling systems. The main function of existing passive decay heat removal systems is feeding additional coolant to the reactor core. Thus, an established emergency core cooling system (ECCS) cannot operate properly because of impossible depressurization under the station blackout (SBO) condition. Therefore, a new concept for passive decay heat removal system is required. In this study, an innovative hybrid control rod concept is considered for passive in-core decay heat removal that differs from the existing direct vessel injection core cooling system and passive auxiliary feedwater system (PAFS). The heat transfer between the evaporator and condenser sections occurs by phase change of the working fluid and capillary action induced by wick structures installed on the inner wall of the heat pipe. In this study, a hybrid control rod is developed to take the roles of both neutron absorption and heat removal by combining the functions of a heat pipe and control rod. Previous studies on enhancing the heat removal capacity of heat pipes used nanofluids, self-rewetting fluids, various wick structures and condensers. Many studies have examined the thermal performances of heat pipes using various nanofluids. They concluded that the enhanced thermal performance of the heat pipe using nanofluids is due to nanoparticle deposition on the wick structures. Thus, the wick structure of heat pipes has been modified by nanoparticle deposition to enhance the heat removal capacity. However, previous studies used relatively small heat pipes and narrow ranges of heat loads. The environment of a nuclear reactor is very specific, and the decay heat produced by fission products after shutdown is relatively large. Thus, this study tested a large-scale heat pipe over a wide range of power. The concept of a hybrid heat pipe for an advanced in-core decay heat removal system was introduced for complete

  16. Heat exposure effects among firefighters

    Directory of Open Access Journals (Sweden)

    Patel Harshad

    2006-01-01

    Full Text Available Background: Firefighting is a hazardous occupation. The firefighters (FF in extinguishing fire are often exposed to extreme heat of 1200oC to 1400oC temperature. The heat exposure effects may occur from hot air, radiant heat, contact with hot surfaces, endogenous heat produced by the body during exercise, which cannot be cooled during fire. A significant morbidity and mortality from exposure to heat was reported in other countries but not from India. Aims : Present study focuses on prevalence of heat exposure effects i.e., heat exhaustion, heat syncope, heat pyrexia and heat cramps recorded among fire fighters of Ahmedabad fire brigade. Settings: Ahmedabad fire brigade (AFB of Ahmedabad municipal corporation. Design: Cross sectional. Materials and Methods: Present study focuses on prevalence of heat exposure effects i.e., heat exhaustion, heat syncope, heat pyrexia and heat cramps recorded between 262 FF of AFB. This prevalence′s were observed among firemen those directly exposed to heat in combating fire and others (load trucks, pump trucks etc. that assist the firemen. These were seen in different age groups (< 30; 31-45 and> 45 yrs, duration of exposure (< 10; 11-20 and> 21 yrs.The number of accidents associated with heat exposure was analyzed. Statistical Analysis: Prevalence comparison by Chi-square test. Results: The results revealed that a total of 53 (20.0% FF reported health exposure effects and were higher among firemen than other groups. Heat exhaustion 48 (18.3%; heat syncope 11(4.2%; heat pyrexia 11 (4.2% and heat cramps 16(6.1% were reported indicating significant occurrence of heat stress among firefighters. In majority of FF, the frequency of occurrence was observed at only one instance. There were no differences according to age or duration of exposure. Among 53 FF with heat exposure effects, accident were reported in 10 (18.9% suggesting that heat stress may be responsible for this. Conclusion: Overall, Significant occurrence

  17. Solitons and ionospheric heating

    Science.gov (United States)

    Weatherall, J. C.; Goldman, M. V.; Sheerin, J. P.; Nicholson, D. R.; Payne, G. L.; Hansen, P. J.

    1982-01-01

    It is noted that for parameters characterizing the Platteville ionospheric heating facility, the Langmuir wave evolution at the exact reflection point of the heater wave involves an oscillating two-stream instability followed by a collisionally damped three-dimensional soliton collapse. The result gives an alternative explanation for certain experimental observations.

  18. Heat exchanger vibration

    International Nuclear Information System (INIS)

    The heat exchangers of various types are common items of plant in the generation and transmission of electricity. The amount of attention given to the flow-induced vibrations of heat exchangers by designers is usually related to the operational history of similar items of plant. Consequently, if a particular design procedure yields items of plant which behave in a satisfactory manner during their operational life, there is little incentive to improve or refine the design procedure. On the other hand, failures of heat exchangers clearly indicate deficiencies in the design procedures or in the data available to the designer. When such failures are attributable to flow-induced vibrations, the identification of the mechanisms involved is a prime importance. Ideally, basic research work provides the background understanding and the techniques necessary to be able to identify the important mechanisms. In practice, the investigation of a flow-induced vibration problem may identify the presence of mechanisms but may not be able to quantify their effects adequately. In these circumstances the need for additional work is established and the objectives of the research programme emerge. The purpose of this paper is to outline the background to the current research programme at C.E.R.L. on heat exchanger vibration

  19. Heat loss from Buildings

    DEFF Research Database (Denmark)

    Karlsson, Kenneth; Næraa, Rikke

    1997-01-01

    Determination of heat loss coefficients for buildings in Denmark. The coefficient are determined for 15 building groups and 3 year intervals. They are based on the BBR-registre and assumptions of U-values(W/K*m2)and computed in a simple spreed sheet model.The results are used in the REVEILLE...

  20. Photovoltaic Roof Heat Flux

    Science.gov (United States)

    Samady, Mezhgan Frishta

    Solar panels were mounted with different designs onto 1:800 scale building models while temperature and radiation were measured. While there have been other studies aimed at finding the optimal angles for solar panels [9], in this study both the angle and the mounting method were tested. The three PV mounting designs that were considered to provide the most insulation to a building's rooftop were flush, offset (control), and angled. The solar panel offset height became a key component for rooftop insulation as well as the performance of the actual solar panel. Experimental results were given to verify the thermal behavior of the heat loads from the different designs of the photovoltaic panel. From the results, the angled PV design needed 16Z more heat extraction than the offset and flush PV design needed 60% more heat extracted than the offset. In addition to the heat transfer analysis, thermal models were performed to incorporate main atmospheric conditions which were based on the effects of PV mounting structure.