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Sample records for prazosin treatment suppresses

  1. Prazosin in the treatment of PTSD.

    PubMed

    Green, Ben

    2014-07-01

    Posttraumatic stress disorder (PTSD) often follows a chronic course, and the disorder is resistant to treatment with antidepressants and cognitive-behavioral therapy in a proportion of patients. Prazosin, an a1-adrenoceptor blocker, has shown some promise in treating chronic PTSD. A review of this literature was conducted via a search of MEDLINE and SUMMON, using keywords such as PTSD, prazosin, treatment, and resistance. At least 10 clinical studies of prazosin in the treatment of PTSD, including open-label and randomized controlled trials, have been published. All of these studies support the efficacy of prazosin either for treating nightmares and improving sleep or for reducing the severity of PTSD. Treatment of PTSD with prazosin is usually initiated at a dose of 1 mg, with monitoring for hypotension after the first dose. The dose is then gradually increased to maintenance levels of 2-6 mg at night. Studies of military patients with PTSD have used higher doses (e.g., 10-16 mg at night). Prazosin has also been studied in younger and older adults with PTSD and in patients with alcohol problems, in whom it was found to reduce cravings and stress responses. Prazosin offers some hope for treating resistant cases of PTSD in which recurrent nightmares are problematic, with a relatively rapid response within weeks. It is suggested that large-scale civilian trials of prazosin be done, as well as studies concerning the use of prazosin in acute PTSD and as a potential preventive agent.

  2. Treatment of Nightmares With Prazosin: A Systematic Review

    PubMed Central

    Kung, Simon; Espinel, Zelde; Lapid, Maria I.

    2012-01-01

    Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports. PMID:22883741

  3. Treatment of nightmares with prazosin: a systematic review.

    PubMed

    Kung, Simon; Espinel, Zelde; Lapid, Maria I

    2012-09-01

    Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports.

  4. Prazosin treatment in the management of scorpion envenomation.

    PubMed

    Peker, Erdal; Oktar, Suleyman; Dogan, Murat; Kaya, Ergun; Duru, Mehmet

    2010-03-01

    Scorpion stings represent an important and serious public health problem worldwide due to their high incidence and potentially severe and often fatal clinical manifestations. Children are at greater risk of developing severe cardiac, respiratory, and neurological complications due to lesser body surface area. Alpha receptor stimulation plays important role in the pathogenesis of pulmonary edema. Prazosin, a post synaptic alpha blocker, can be recommended as an effective drug in the treatment of serious scorpion envenomations with significant sympathetic symptoms. Oral prazosin is fast acting, easily available, relatively cheap, free from any anaphylaxis and highly effective.

  5. Prazosin for Treatment of Patients with PTSD and Comorbid Alcohol Dependence

    DTIC Science & Technology

    2011-07-01

    08-2-0075 TITLE: Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR: Ismene...page. Subject terms on next page. 6 Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence Ismene Petrakis Yale University New...PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-! adrenergic •ceptor antagonist

  6. Comparison of terazosin and prazosin for treatment of vesico-urethral reflex dyssynergia in dogs.

    PubMed

    Haagsman, A N; Kummeling, A; Moes, M E; Mesu, S J; Kirpensteijn, J

    2013-07-13

    Nineteen dogs with vesico-urethral reflex dyssynergia (VURD) were treated with prazosin or terazosin 0.5 mg/kg twice daily to compare efficacy and side effects. Dogs were referred because of signs of (partial) urethral obstruction. Physical examination, abdominal ultrasonography, urinalysis and a radiographic contrast study of bladder and urethra (urethrocystography) were routinely performed. If no mechanical causes of obstruction or disease of the distal urinary tract were observed, the diagnosis VURD was presumed and the dogs were included in our study. Follow-up information was obtained from owners or referring veterinarians. Significantly more side effects were seen in the dogs treated with terazosin (n=14; 93 per cent) compared with the dogs treated with prazosin (n=5; 20 per cent; P=0.002). Effects of the treatment were comparable between prazosin and terazosin. Labradors and dogs that were castrated surgically had a significant better survival (P<0.01) compared with other breeds and animals that were castrated chemically. There was a moderate to good effect in 60 per cent of the dogs treated with prazosin, and in 64 per cent of the dogs treated with terazosin.

  7. Prazosin for Treatment of Patients with PTSD and Comorbid Alcohol Dependence

    DTIC Science & Technology

    2014-12-01

    Prazosin for Treatment of Patients with PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR...of Patients with PTSD and Comorbid Alcohol Dependence 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-2-0075 5c. PROGRAM ELEMENT NUMBER 6...comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of TSD among individuals with AD are at least twice

  8. Re-emergence of posttraumatic stress disorder nightmares with nursing home admission: treatment with prazosin.

    PubMed

    Johnson, Kim G; Rosen, Jules

    2013-02-01

    Seniors with a history of emotional trauma decades earlier can experience a recurrence of posttraumatic stress disorder symptoms when transitioning to a nursing home. We present the case of an 86-year-old male Holocaust survivor admitted to a nursing home for physical therapy and rehabilitation 6 weeks after the death of his wife; the patient was expressing a persistent death wish. Despite the multiple risk factors for depression, his distress was specifically related to the reemergence of nightly posttraumatic nightmares. Over the course of 1 week of treatment with 1 mg prazosin at bedtime, his nightmares and his death wish completely resolved. He achieved his rehabilitation goals and was discharged to a community setting. This report highlights the importance of considering posttraumatic stress disorder in nursing home residents with a history of emotional trauma, and understanding how to address these symptoms pharmacologically and nonpharmacologically.

  9. Preliminary findings concerning the use of prazosin for the treatment of posttraumatic nightmares in a refugee population.

    PubMed

    Boynton, Lorin; Bentley, Jacob; Strachan, Eric; Barbato, Anna; Raskind, Murray

    2009-11-01

    Prazosin, a centrally active alpha-1 adrenergic receptor antagonist, has reduced nightmares and sleep disturbances in placebo-controlled studies involving patients with combat and civilian related posttraumatic stress disorder (PTSD). In this retrospective chart review, we analyzed data from 23 refugees diagnosed with chronic PTSD who were treated with prazosin. The recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS) was used to quantify nightmare severity. A Clinical Global Impressions-Change (CGI-C) score assessed change in overall PTSD severity exclusive of nightmares. Using a paired-samples t-test, we found that CAPS scores decreased significantly (p <0.0005) from baseline after 8 weeks of treatment with a stable dose of prazosin. Overall PTSD severity was "markedly improved" in 6 patients, "moderately improved" in 11 patients, and "minimally improved" in 6 patients. These data provide preliminary support for the use of prazosin in targeting reduction of trauma-related nightmares and promoting improvement of global clinical status within an international sample of severely traumatized refugee patients.

  10. Prazosin treatment of trauma nightmares and sleep disturbance in soldiers deployed in Iraq.

    PubMed

    Calohan, Jess; Peterson, Kris; Peskind, Elaine R; Raskind, Murray A

    2010-10-01

    Trauma nightmares and sleep disturbance impair combat soldiers' functioning. The alpha-1 adrenoreceptor antagonist prazosin has been demonstrated effective for these symptoms in Vietnam veterans. Thirteen soldiers seeking relief from distressing trauma nightmares impairing military function in northern Iraq in 2006 received prazosin alone or in combination with other psychotropics. Mean prazosin dose was 4.1 (SD = 2.2) mg before bed. Six soldiers improved markedly and 3 moderately on the Clinical Global Impression of Change Ratings of distressing dreams decreased from an average of 7.0 (SD = 0.7) to 2.9 (SD = 3.0, p < .001) and those of disturbed sleep from 6.7 (SD = 0.9) to 3.7 (SD = 2.4, p < .001). Prazosin appears effective and well tolerated in the desert warfare environment.

  11. Adenosine 3',5'-cyclic monophosphate involvement in hepatic triacylglyceride lipase release from prazosin-stimulated primary cultured rat hepatocytes.

    PubMed

    Nakamura, Tetsuya; Morita, Tetsuo

    2014-01-01

    We recently found that hepatic triglyceride lipase (HTGL) was released from primary cultured rat hepatocytes after treatment with prazosin, an antagonist of alpha-1 adrenoceptors. However, the details of prazosin-induced HTGL release remain uncertain. Here we investigated whether changes in cAMP levels in hepatocytes were related to HTGL release from prazosin-stimulated hepatocytes. When hepatocytes were treated with prazosin, cAMP levels during stimulated release of HTGL increased in a time- and dose-dependent manner. Stimulated release of HTGL was suppressed by the adenylate cyclase inhibitors MDL-12,330A and 2',5'-dideoxyadenosine. Further, cAMP-dependent protein kinase A (PKA) activity in prazosin-stimulated hepatocytes also increased in a time- and dose-dependent manner. Moreover, prazosin-stimulated HTGL release was suppressed by the PKA inhibitors H-89 and KT5720. These results suggest that prazosin-stimulated HTGL release from hepatocytes was due to cAMP production and partly due to subsequent PKA activation in hepatocytes.

  12. Prazosin Can Prevent Glucocorticoid Mediated Capillary Rarefaction

    PubMed Central

    Mandel, Erin R.; Dunford, Emily C.; Trifonova, Anastassia; Abdifarkosh, Ghoncheh; Teich, Trevor; Riddell, Michael C.

    2016-01-01

    Glucocorticoids (GC) elicit skeletal muscle capillary rarefaction, which can subsequently impair blood distribution and muscle function; however, the mechanisms have not been established. We hypothesized that CORT would inhibit endothelial cell survival signals but that treatment with the alpha-1 adrenergic receptor inhibitor prazosin, which leads to angiogenesis in skeletal muscle of healthy rats, would reverse these effects and induce angiogenesis within the skeletal muscle of corticosterone (CORT)-treated rats. Male Sprague Dawley rats were implanted subcutaneously with CORT pellets (400 mg/rat), with or without concurrent prazosin treatment (50mg/L in drinking water), for 1 or 2 weeks. Skeletal muscle capillary rarefaction, as indicated by a significant reduction in capillary-to-fiber ratio (C:F), occurred after 2 weeks of CORT treatment. Concurrent prazosin administration prevented this capillary rarefaction in CORT-treated animals but did not induce angiogenesis or arteriogenesis as was observed with prazosin treatment in control rats. CORT treatment reduced the mRNA level of Angiopoietin-1 (Ang-1), which was partially offset in the muscles of rats that received 2 weeks of co-treatment with prazosin. In 2W CORT animals, prazosin treatment elicited a significant increase in vascular endothelial growth factor-A (VEGF-A) mRNA and protein. Conversely prazosin did not rescue CORT-induced reductions in transforming growth factor beta-1 (TGFβ1 and matrix metalloproteinase-2 (MMP-2) mRNA. To determine if CORT impaired shear stress dependent signaling, cultured rat skeletal muscle endothelial cells were pre-treated with CORT (600nM) for 48 hours, then exposed to 15 dynes/cm2 shear stress or maintained with no flow. CORT blunted the shear stress-induced increase in pSer473 Akt, while pThr308 Akt, ERK1/2 and p38 phosphorylation and nitric oxide (NO) production were unaffected. This study demonstrates that GC-mediated capillary rarefaction is associated with a reduction

  13. Prazosin Can Prevent Glucocorticoid Mediated Capillary Rarefaction.

    PubMed

    Mandel, Erin R; Dunford, Emily C; Trifonova, Anastassia; Abdifarkosh, Ghoncheh; Teich, Trevor; Riddell, Michael C; Haas, Tara L

    2016-01-01

    Glucocorticoids (GC) elicit skeletal muscle capillary rarefaction, which can subsequently impair blood distribution and muscle function; however, the mechanisms have not been established. We hypothesized that CORT would inhibit endothelial cell survival signals but that treatment with the alpha-1 adrenergic receptor inhibitor prazosin, which leads to angiogenesis in skeletal muscle of healthy rats, would reverse these effects and induce angiogenesis within the skeletal muscle of corticosterone (CORT)-treated rats. Male Sprague Dawley rats were implanted subcutaneously with CORT pellets (400 mg/rat), with or without concurrent prazosin treatment (50mg/L in drinking water), for 1 or 2 weeks. Skeletal muscle capillary rarefaction, as indicated by a significant reduction in capillary-to-fiber ratio (C:F), occurred after 2 weeks of CORT treatment. Concurrent prazosin administration prevented this capillary rarefaction in CORT-treated animals but did not induce angiogenesis or arteriogenesis as was observed with prazosin treatment in control rats. CORT treatment reduced the mRNA level of Angiopoietin-1 (Ang-1), which was partially offset in the muscles of rats that received 2 weeks of co-treatment with prazosin. In 2W CORT animals, prazosin treatment elicited a significant increase in vascular endothelial growth factor-A (VEGF-A) mRNA and protein. Conversely prazosin did not rescue CORT-induced reductions in transforming growth factor beta-1 (TGFβ1 and matrix metalloproteinase-2 (MMP-2) mRNA. To determine if CORT impaired shear stress dependent signaling, cultured rat skeletal muscle endothelial cells were pre-treated with CORT (600nM) for 48 hours, then exposed to 15 dynes/cm2 shear stress or maintained with no flow. CORT blunted the shear stress-induced increase in pSer473 Akt, while pThr308 Akt, ERK1/2 and p38 phosphorylation and nitric oxide (NO) production were unaffected. This study demonstrates that GC-mediated capillary rarefaction is associated with a reduction

  14. Two Case Reports on Use of Prazosin for Drug Dreams.

    PubMed

    Gopalakrishna, Ganesh; Popoola, Oluwole; Campbell, Austin; Nemetalla, Marina A

    2016-01-01

    Substance abuse and dependence is estimated to cost roughly $700 billion annually including direct and indirect care in the United States. Drug dreams (DD), or using dreams, are a reportedly common phenomenon among patients with substance abuse, and have been postulated as triggers for relapse. Prazosin is an alpha-1 receptor antagonist originally approved by the United States Food and Drug Administration for the treatment of hypertension. Prazosin passes the blood brain barrier easily, contributing to central and cognitive effects. Prazosin's efficacy has been demonstrated in the management of posttraumatic stress disorder (PTSD), and associated nightmares. We present the cases of two patients with substance use disorder experiencing DD which resolved after the addition of prazosin during an acute psychiatric hospitalization. To our knowledge, this is the first time treatment of DD with prazosin has been reported in the literature. Both patients reported an alleviation of their DD after the medication was initiated. The effect was immediate and results were seen on the same night of the initial dose. The precise mechanism of this effect is unclear, but we hypothesize it is related to the decrease in noradrenaline effects at α-1 adrenoreceptors in the brain, similar to the effect on nightmares in PTSD. The key limitation is the low number of patients and lack of follow up presented in this report. No causal relationship can be established between the use of prazosin and resolution of DD in our patients.

  15. Prazosin induces p53-mediated autophagic cell death in H9C2 cells.

    PubMed

    Yang, Yi-Fan; Wu, Chau-Chung; Chen, Wen-Pin; Chen, Yuh-Lien; Su, Ming-Jai

    2011-08-01

    Prazosin, a quinazoline-based α(1)-adrenoceptor antagonist, is known to induce cell death, and this effect is independent of its α-blockade activity. However, the detailed molecular mechanisms involved are still not fully understood. In this study, we found that prazosin, but not doxazosin, could induce patterns of autophagy in H9C2 cells, including intracellular vacuole formation, microtubule-associated protein 1 light chain 3 (LC3) conversion, and acidic vesicular organelle (AVO) augmentation. Western blot analysis of phosphorylated proteins showed that exposure to prazosin increased the levels of phospho-p53 and phospho-adenosine monophosphate-activated protein kinase (AMPK) but dramatically decreased the levels of phospho-mammalian target of rapamycin (mTOR), phospho-protein kinase B (Akt), and phospho-ribosomal protein S6 kinase (p70S6K). Furthermore, although pretreatments with the pharmacological autophagy inhibitor 3-methyladenine and the p53 inhibitor pifithrin-α suppressed prazosin-induced AVO formation, they did not reverse prazosin-induced decline in cell viability but enhanced prazosin-induced caspase-3 activation. From these results we suggest that prazosin induces autophagic cell death via a p53-mediated mechanism. When the autophagy pathway was inhibited, prazosin still induced programmed cell death, at least in part through apoptotic caspase-3 cascade enhancement. Thus, our results indicate a potential new target in prazosin-induced cell death.

  16. Haemodynamic and hormonal effects of prazosin on head-up tilt in essential hypertensive patients: comparison with those of propranolol.

    PubMed

    Kida, O; Morotomi, Y; Higa, T; Kodama, K; Someya, N; Tanaka, K

    1984-01-01

    To evaluate the haemodynamic and hormonal effects of prazosin, head-up tilt was performed in 10 essential hypertensive patients, and these effects of prazosin on the tilt were compared with those of propranolol. The tilts were performed in control phase and the last days of treatment for two weeks with propranolol (90 mg/day) or prazosin (3-6 mg/day). Each drug significantly lowered the mean blood pressure at rest, and also suppressed its rise on the tilt. Heart rates were significantly increased by the tilt in the control phase, in the propranolol phase and in the prazosin phase. Cardiac index was significantly reduced by the tilt from 2.66 (s.e.m. = 0.22) 1/min per m2 to 2.08 (s.e.m. = 0.20) in the propranolol phase. However, there were not significant changes in other phases. Total peripheral resistance indices were significantly increased by the tilt in all three phases. Plasma renin activity and plasma aldosterone were significantly increased by the tilt from 2.14 (s.e.m. = 0.47) ng/ml per h to 2.46 (s.e.m. = 0.54) and from 50.6 (s.e.m. = 12.9) pg/ml to 74.9 (s.e.m. = 14.9) respectively, in the control phase. And they were also significantly increased from 1.06 (s.e.m. = 0.29) to 1.65 (s.e.m. = 0.45) and from 41.4 (s.e.m. = 16.3) to 54.0 (s.e.m. = 17.4) in the prazosin phase. There were no significant increases during the administration of propranolol. We observed that prazosin did not alter heart rate and cardiac index, but suppressed the renin-angiotensin system at rest. It is suggested that prazosin did not influence haemodynamic and hormonal responses to the tilt.

  17. Prazosin Augmentation of Outpatient Treatment of Alcohol Use Disorders in Active Duty Soldiers with and without PTSD

    DTIC Science & Technology

    2015-10-01

    Substance Abuse Program (ASAP) at Madigan Health Care System/Joint Base Lewis McChord. The aims of this trial are 1) to determine prazosin’s efficacy... Abuse Program (ASAP) at Madigan HCS/Joint Base Lewis McChord. The aims of this trial are 1) to determine prazosin’s efficacy for AUD in OIF/OEF soldiers...Augmentation of Outpatient Treatment of AUD in Active Duty Soldiers with and without PTSD. Presented at Joint Army/NIH Substance Abuse IP – September 29

  18. Prazosin

    MedlinePlus

    ... organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other ... hyperplasia (BPH, noncancerous enlargement of the prostate), congestive heart failure, pheochromocytoma (adrenal gland tumor), sleep problems associated with ...

  19. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin.

    PubMed

    Sattin, Albert; Pekary, Albert Eugene; Blood, James

    2011-08-01

    Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder (PTSD). Prazosin, a brain-active blocker of α(1)-adrenoceptors, originally used for the treatment of hypertension, has been reported to alleviate trauma nightmares, sleep disturbance and improve global clinical status in war veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) may play a role in the pathophysiology and treatment of neuropsychiatric disorders such as major depression, and PTSD (an anxiety disorder). To investigate whether TRH or TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) participate in the therapeutic effects of prazosin, male rats were injected with prazosin and these peptides then measured in brain and endocrine tissues. Prazosin stimulated TRH and TRH-like peptide release in those tissues with high α(1)-adrenoceptor levels suggesting that these peptides may play a role in the therapeutic effects of prazosin.

  20. Prazosin for Trauma Nightmares and Sleep Disturbances in Combat Veterans with Post-Traumatic Stress Disorder

    PubMed Central

    Khazaie, Habibolah; Nasouri, Marzie; Ghadami, Mohammad Rasoul

    2016-01-01

    Background Prazosin is significantly effective to reduce sleep disturbance and trauma nightmare in patients with post-traumatic stress disorder (PTSD); however, results of different studies were evaluated. Objectives The current randomized clinical trial aimed to assess the effects of prazosin on sleep parameters and nightmares among veterans with chronic PTSD. Materials and Methods Thirty-two veterans with chronic war-induced PTSD and distressing nightmares were randomized into prazosin and placebo groups for eight weeks. The main symptoms were qualified using the recurrent distressing dreams item of the clinician administered PTSD scale (CAPS) and the daytime symptom severity was measured by PTSD checklist (PCL) and the objective sleep quality assessment by actigraphy. Results Compared with placebo, prazosin had no significant effects on reduction of daytime symptoms (P = 0.69) and frequency and intensity of trauma-related nightmares. Also, there were no significant differences between pre- and post-treatment actigraphy measurements (P > 0.05). Conclusions The study findings showed that prazosin had no significant effect on reduction of PTSD symptoms as well as nightmares among veterans with chronic PTSD. Further clinical trials are needed to define the effect of prazosin on sleep physiology and whether such effects regarding the therapeutic response. PMID:27822278

  1. DEVELOPMENT OF NOVEL, ALTERNATIVE, FACILE, ECOFRIENDLY, HIGH YIELD SYNTHETIC PROCESS FOR PRAZOSIN

    PubMed Central

    Patil, D. A.; Jain, K. S.; Deodhar, M. N.; Patil, P. O.; Patil, G. B.; Patil, D. D.

    2010-01-01

    Industrial chemistry in the new millennium is widely adopting the concept of “Green chemistry” to meet the fundamental scientific challenges. Antihypertensive drugs include several of the most widely prescribed drugs like diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, and α-1 adrenoreceptor blockers. The discovery of prazosin, with very high index of α1/α2 affinity has triggered off a renaissance of interest in α1-adrenoceptor antagonist drugs for treatment of hypertension. The three reported routes for synthesis and manufacture of the α-adrenoceptor antagonist- prazosin had some disadvantages. In present study we had developed new methods for the synthesis of prazosin by using microwave. The most important aspect is the overall yield of this process was ~25 % higher than the other reported methods excluding the use of banned substances PMID:24825992

  2. Prazosin for military combat-related PTSD nightmares: a critical review.

    PubMed

    Writer, Brian W; Meyer, Eric G; Schillerstrom, Jason E

    2014-01-01

    Military combat is a common trauma experience associated with posttraumatic stress disorder (PTSD). Trauma-related nightmares are a hallmark symptom of PTSD. They can be resistant to label-pharmacological PTSD treatment, and they are associated with a variety of adverse health outcomes. The purpose of this article is to review and evaluate prazosin therapy for combat-related PTSD nightmares. Consistent with available literature for all-causes PTSD nightmares, prazosin is an effective off-label option for combat-related PTSD nightmares. Future trials may further instruct use in specific combat-exposure profiles.

  3. Comparative Meta-Analysis of Prazosin and Imagery Rehearsal Therapy for Nightmare Frequency, Sleep Quality, and Posttraumatic Stress

    PubMed Central

    Seda, Gilbert; Sanchez-Ortuno, Maria M.; Welsh, Carolyn H.; Halbower, Ann C.; Edinger, Jack D.

    2015-01-01

    Study Objective: In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS). Methods: Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy. Results: Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01). Conclusion: Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted. Commentary: A commentary on this article appears in this issue on page 9. Citation: Seda G, Sanchez-Ortuno MM, Welsh CH, Halbower AC, Edinger JD. Comparative meta-analysis of prazosin and imagery rehearsal therapy for nightmare frequency, sleep quality, and posttraumatic stress. J Clin Sleep Med 2015;11(1):11

  4. Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects.

    PubMed

    Abraham, Renny; Nirogi, Ramakrishna; Shinde, Anil; Irupannanavar, Shantaveer

    2015-01-01

    An extensive amount of research has focused on the development of new pharmacological agents to treat schizophrenia. Varying from person to person, schizophrenia is a heterogeneous disease with symptoms of positive, negative, and cognitive deficits. PRX-07034, a 5-hydroxytryptamine6 (5-HT6) receptor antagonist has been evaluated for its potential in treating obesity and cognitive deficits. This study evaluated PRX-07034 (0.1, 0.3, and 1.0 mg/kg body mass, by intraperitoneal (i.p.) injection), in combination with a low dose of prazosin (0.3 mg/kg, i.p.), for its antipsychotic potential. The research utilized a stereotypy assay, an open field test, an object recognition task, and prepulse inhibition. Dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist, was also administered in the above-mentioned assays as a psychomimetic. The combination of PRX-07034 and prazosin alleviated stereotypy and hyperlocomotor activity while enhancing memory in an object recognition task, and reversed sensory-gating deficits induced by dizocilpine. Examination of the medial prefrontal cortex revealed that a combination of PRX-07034 and prazosin reduced the dizocilpine-mediated increase of 5-HT. These results suggest that the combination of a 5-HT6 antagonist with low doses of prazosin could have therapeutic potential in the treatment of schizophrenia.

  5. Prazosin lowers plasma triglyceride concentration in rats: a preliminary report.

    PubMed

    Reaven, G M; Dall'Aglio, E

    1982-01-01

    Prazosin was administered by intraperitoneal injection (0.3 or 3.0 mg/kg) to normal chow-fed male rats for 14 days. Mean +/- SEM plasma triglyceride levels were lower (p less than 0.001) in the prazosin-treated rats (74 +/- 12 mg/dl and 72 +/- 9 mg/dl) than in saline-injected control rats (115 +/- 11 mg/dl). This effect was associated with commensurate reductions in very low density lipoprotein-triglyceride secretion in prazosin-treated rats. No changes were noted in either plasma total or high density lipoprotein cholesterol concentrations. In addition, prazosin was capable of reducing by approximately 50% the elevation in plasma triglyceride concentration produced by a high glucose diet in control rats. The mechanism of the observed effect of prazosin on very low density lipoprotein metabolism in the rat remains to be defined.

  6. Sleep Disturbances and Nightmares in a Patient Treated with Prazosin.

    PubMed

    Kosari, Sam; Naunton, Mark

    2016-04-15

    Prazosin is increasingly being used off-label to treat nightmares in patients with posttraumatic stress disorder. The literature about the psychiatric adverse effects of prazosin is very limited. We present a case in which low-dose prazosin was associated with nightmares and sleep disturbances in an elderly patient without previously diagnosed mental illness or coexisting environmental risk factors for nightmares. Insomnia and hallucinations are listed as some of the rare side effects of prazosin by the manufacturer. Prazosin could be associated with rare psychiatric adverse effects and sleep disturbances. Particular attention is required in identifying these adverse effects, which can be difficult to distinguish from other drug-related side effects in the elderly particularly because they are often using multiple medications.

  7. Investigation of the atypical glass transition and recrystallization behavior of amorphous prazosin salts.

    PubMed

    Kumar, Lokesh; Popat, Dharmesh; Bansal, Arvind K

    2011-08-25

    This manuscript studied the effect of counterion on the glass transition and recrystallization behavior of amorphous salts of prazosin. Three amorphous salts of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin tosylate were prepared by spray drying, and characterized by optical-polarized microscopy, differential scanning calorimetry and powder X-ray diffraction. Modulated differential scanning calorimetry was used to determine the glass transition and recrystallization temperature of amorphous salts. Glass transition of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ~ prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed glass transition, followed by recrystallization. In contrast, amorphous prazosin hydrochloride showed glass transition and recrystallization simultaneously. Density Functional Theory, however, suggested the expected order of glass transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The counterintuitive observation of amorphous prazosin hydrochloride having lower glass transition was explained in terms of its lower activation energy (206.1 kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further correlated to a difference in hydrogen bonding strength of the amorphous and the corresponding recrystallized salts. This study has implications in selection of an optimal amorphous salt form for pharmaceutical development.

  8. The alpha1-adrenergic receptor antagonists, benoxathian and prazosin, induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells.

    PubMed

    Fuchs, Robert; Stelzer, Ingeborg; Haas, Helga S; Leitinger, Gerd; Schauenstein, Konrad; Sadjak, Anton

    2009-10-01

    The erythroleukemia cell lines K562 and human erythroleukemia (HEL) are established models to study erythroid and megakaryocytic differentiation in vitro. In this study, we show that the alpha1-adrenergic antagonists, benoxathian and prazosin, inhibit the proliferation and induce apoptosis in K562 and HEL cells. Furthermore, both tested substances induced the expression of the megakaryocytic marker CD41a, whereas the expression of the erythroid marker glycophorin-a was decreased or unchanged. Even though the expression of differentiation markers was similar after benoxathian and prazosin treatment in both cell lines, endomitosis of erythroleukemia cells was observed only after prazosin treatment. So far, benoxathian and prazosin are the first described extracellular ligands, which cause megakaryocytic differentiation in K562 and HEL cells. In summary, these results indicate a possible role of alpha1-adrenergic receptor signaling in the regulation of erythroid and megakaryocytic differentiation, even though the receptor dependence of the observed effects needs further investigation.

  9. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use Disorders with and without Co-Occurring PTSD

    DTIC Science & Technology

    2016-01-01

    despite recent gains in establishing effective pharmacological and behavioral treatments for alcohol use disorders (AUD), nonremittance and relapse...including PTSD status, moderate medication response. 15. SUBJECT TERMS Alcohol Drinking, Drinking Behavior , Naltrexone, Prazosin, Adrenergic Agents...Provide a brief list of keywords (limit to 20 words). Alcohol Drinking  Drinking  Behavior   Alcohol Craving  Naltrexone  Prazosin  Adrenergic Agents

  10. The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats.

    PubMed

    Dunford, Emily C; Leclair, Erwan; Aiken, Julian; Mandel, Erin R; Haas, Tara L; Birot, Olivier; Riddell, Michael C

    2017-03-01

    Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C:F) in streptozotocin (STZ)-treated diabetic rats. STZ (65 mg/kg) was intraperitoneally administered to male Sprague-Dawley rats (n = 36) to induce diabetes, with healthy, nondiabetic, sedentary rats (n = 10) as controls. The STZ-treated rats were then divided into sedentary (SED) or exercising (EX; 24-h access to running wheels) groups and then further subdivided into prazosin (Praz) or water (H2O) treatment groups: nondiabetic-SED-H2O, STZ-SED-H2O, STZ-EX-H2O, STZ-SED-Praz, and STZ-EX-Praz. After 3 wk, untreated diabetes significantly reduced the C:F in tibialis anterior (TA) and soleus muscles in the STZ-SED-H2O animals (both P < 0.05). Voluntary exercise and prazosin treatment independently resulted in a normalization of C:F within the TA (1.86 ± 0.12 and 2.04 ± 0.03 vs 1.71 ± 0.09, P < 0.05) and the soleus (2.36 ± 0.07 and 2.68 ± 0.14 vs 2.13 ± 0.12, P < 0.05). The combined STZ-EX-Praz group resulted in the highest C:F within the TA (2.26 ± 0.07, P < 0.05). Voluntary exercise volume was negatively correlated with fed blood glucose levels (r(2) = -0.7015, P < 0.01) and, when combined with prazosin, caused further enhanced nonfasted glucose (P < 0.01). Exercise and prazosin reduced circulating nonesterified fatty acids more than either stimulus alone (P < 0.05). These results suggest that the distinct stimulation of angiogenesis, with both regular exercise and prazosin treatment, causes a cooperative improvement in the microvascular complications associated with T1D.NEW & NOTEWORTHY It is currently well established that poorly controlled diabetes

  11. Effect of counterion on the solid state photodegradation behavior of prazosin salts.

    PubMed

    Kumar, Lokesh; Jog, Rajan; Singh, Saranjit; Bansal, Arvind

    2013-06-01

    The effect of counterion was evaluated on the photodegradation behavior of six prazosin salts, viz., prazosin hydrochloride anhydrous, prazosin hydrochloride polyhydrate, prazosin tosylate anhydrous, prazosin tosylate monohydrate, prazosin oxalate dihydrate, and prazosin camsylate anhydrous. The salts were subjected to UV-Visible irradiation in a photostability test chamber for 10 days. The samples were analyzed for chemical changes by a specific stability-indicating high-performance liquid chromatography method. pH of the microenvironment was determined in 10%w/v aqueous slurry of the salts. The observed order of photostability was: prazosin hydrochloride anhydrous>prazosin camsylate anhydrous~prazosin-free base>prazosin hydrochloride polyhydrate>prazosin tosylate anhydrous>prazosin oxalate dihydrate~prazosin tosylate monohydrate. Multivariate analysis of the photodegradation behavior suggested predominant contribution of the state of hydration and also intrinsic photosensitivity of the counterion. Overall, hydrated salts showed higher photodegradation compared to their anhydrous counterparts. Within the anhydrous salts, aromatic and carbonyl counterion-containing salts showed higher susceptibility to light. The pH of microenvironment furthermore contributed to photodegradation of prazosin salts, especially for drug counterions with inherent higher pH. The study reveals importance of selection of a suitable drug salt form for photosensitive drugs during preformulation stage of drug development.

  12. Geographical diffusion of prazosin across Veterans Health Administration: Examination of regional variation in daily dosing and quality indicators among veterans with posttraumatic stress disorder.

    PubMed

    Abrams, Thad E; Lund, Brian C; Alexander, Bruce; Bernardy, Nancy C; Friedman, Matthew J

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the Veterans Health Administration (VHA), and dissemination patterns of innovative, efficacious therapies can inform areas for potential improvement of diffusion efforts and quality prescribing. In this study, we replicated a prior examination of the period prevalence of prazosin use as a function of distance from Puget Sound, Washington, where prazosin was first tested as an effective treatment for PTSD and where prazosin use was previously shown to be much greater than in other parts of the United States. We tested the following three hypotheses related to prazosin geographic diffusion: (1) a positive geographical correlation exists between the distance from Puget Sound and the proportion of users treated according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d), (2) an inverse geographic correlation exists between prazosin and benzodiazepine use, and (3) no geographical correlation exists between prazosin use and serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%, whereas utilization rates at locations a minimum of 2,500 miles away increased from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the Puget Sound location. In contrast, at distances of at least 2,500 miles from Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to 17.7%). No discernible association was demonstrated between SSRI/SNRI or benzodiazepine utilization and the geographic distance from Puget Sound. Minimal threshold dosing of prazosin correlated positively with increased diffusion of prazosin use, but there was still a distance diffusion gradient. Although prazosin adoption has improved, geographic

  13. The α1 adrenoceptor antagonist prazosin enhances sleep continuity in fear-conditioned Wistar-Kyoto rats.

    PubMed

    Laitman, Benjamin M; Gajewski, Nicholas D; Mann, Graziella L; Kubin, Leszek; Morrison, Adrian R; Ross, Richard J

    2014-03-03

    Fragmentation of rapid eye movement sleep (REMS) is well described in individuals with posttraumatic stress disorder (PTSD) and likely has significant functional consequences. Fear-conditioned rodents may offer an attractive model of the changes in sleep that characterize PTSD. Following fear conditioning (FC), Wistar-Kyoto (WKY) rats, a strain known to be particularly stress-sensitive, have increased REMS fragmentation that can be quantified as a shift in the distribution of REMS episodes towards the more frequent occurrence of sequential REMS (inter-REMS episode interval≤3 min) vs. single REMS (interval>3 min). The α1 adrenoceptor antagonist prazosin has demonstrated efficacy in normalizing sleep in PTSD. To determine the utility of fear-conditioned WKY rats as a model of sleep disturbances typical of PTSD and as a platform for the development of new treatments, we tested the hypothesis that prazosin would reduce REMS fragmentation in fear-conditioned WKY rats. Sleep parameters and freezing (a standard measure of anxiety in rodents) were quantified at baseline and on Days 1, 7, and 14 following FC, with either prazosin (0.01mg/kg, i.p.) or vehicle injections administered prior to testing in a between-group design. Fear conditioning was achieved by pairing tones with a mild electric foot shock (1.0mA, 0.5s). One, 7, and 14 days following FC, prazosin or vehicle was injected, the tone was presented, freezing was measured, and then sleep was recorded from 11 AM to 3 PM. WKY rats given prazosin, compared to those given vehicle, had a lower amount of seq-REMS relative to total REMS time 14 days after FC. They also had a shorter non-REMS latency and fewer non-REMS arousals at baseline and on Days 1 and 7 after FC. Thus, in FC rats, prazosin reduced both REMS fragmentation and non-REMS discontinuity.

  14. Terazosin, doxazosin, and prazosin: current clinical experience.

    PubMed

    Akduman, B; Crawford, E D

    2001-12-01

    Lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction are common in aging men. Nearly 25% of men >40 years of age have LUTS. Medical therapy with alpha-blockade is the most common method of medical therapy for benign prostatic obstruction. Multiple methods of minimally invasive surgical therapies have been introduced in the last decade. These methods include balloon dilatation, temporary and permanent urethral stents, various laser techniques, microwave thermotherapy, transurethral needle ablation, electrovaporization, and high-intensity focused ultrasound. alpha-Receptor blockers to reduce the sympathetic tone of the prostate are considered as first-line therapy to relieve the symptoms of benign prostatic hyperplasia. Selective alpha(1)-receptor blockers relax prostatic smooth muscle, relieve bladder outlet obstruction, and enhance urine flow with fewer side effects. In addition, it was determined that treating patients with alpha-blockers increases prostatic apoptosis. Pharmacokinetic activity, mode of action, clinical efficacy, and side effects of the selective alpha(1)-receptor blockers terazosin, doxazosin, and prazosin are reviewed.

  15. Prazosin versus quetiapine for nighttime posttraumatic stress disorder symptoms in veterans: an assessment of long-term comparative effectiveness and safety.

    PubMed

    Byers, Melanie G; Allison, Kristen M; Wendel, Christopher S; Lee, Jeannie K

    2010-06-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population.

  16. Cytokine treatment of macrophage suppression of T cell activation.

    PubMed

    Silberman, Daniel; Bucknum, Amanda; Kozlowski, Megan; Matlack, Robin; Riggs, James

    2010-01-01

    High Mphi:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNgamma-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mphi expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mphi:T cell ratios found in many tumors.

  17. Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD.

    PubMed

    Feenstra, Matthijs G P; Klompmakers, André; Figee, Martijn; Fluitman, Sjoerd; Vulink, Nienke; Westenberg, Herman G M; Denys, Damiaan

    2016-02-01

    The efficacy of selective serotonin reuptake inhibitors (SRIs) in psychiatric disorders may be "augmented" through the addition of atypical antipsychotic drugs. A synergistic increase in dopamine (DA) release in the prefrontal cortex has been suggested to underlie this augmentation effect, though the mechanism of action is not clear yet. We used in vivo microdialysis in rats to study DA release following the administration of combinations of fluvoxamine (10 mg/kg) and quetiapine (10 mg/kg) with various monoamine-related drugs. The results confirmed that the selective 5-HT1A antagonist WAY-100635 (0.05 mg/kg) partially blocked the fluvoxamine-quetiapine synergistic effect (maximum DA increase dropped from 325% to 214%). A novel finding is that the α1-adrenergic blocker prazosin (1 mg/kg), combined with fluvoxamine, partially mimicked the effect of augmentation (maximum DA increase 205%; area-under-the-curve 163%). As this suggested that prazosin augmentation might be tested in a clinical study, we performed an open clinical trial of prazosin 20 mg addition to SRI in therapy-resistant patients with obsessive-compulsive disorder applying for neurosurgery. A small, non-significant reduction in Yale Brown Obsessive Compulsive Scale (Y-BOCS) scores was observed in 10 patients and one patient was classified as a responder with a reduction in Y-BOCS scores of more than 25%. We suggest that future clinical studies augmenting SRIs with an α1-adrenergic blocker in less treatment resistant cases should be considered. The clinical trial "Prazosin in combination with a serotonin reuptake inhibitor for patients with Obsessive Compulsive disorder: an open label study" was registered at 24/05/2011 under trial number ISRCTN61562706: http://www.controlled-trials.com/ISRCTN61562706.

  18. The Specific α1-Adrenergic Receptor Antagonist Prazosin Influences the Urine Proteome

    PubMed Central

    Zhao, Mindi; Wu, Jianqiang; Gao, Youhe

    2016-01-01

    Urine, reflecting many changes in the body, is a better source than blood for biomarker discovery. However, even under physiological conditions, the urine proteome often varies. Understanding how various regulating factors affect urine proteome helps link changes to urine proteome with urinary biomarkers of physiological conditions as well as corresponding diseases. To evaluate the possible impact of α1-adrenergic receptor on urine proteome, this study investigated effects of the specific inhibitor prazosin on the urine proteome in a rat model by using tandem mass tagging and two-dimensional liquid chromatography-tandem mass spectrometry. A total of 775 proteins were identified, approximately half of which were influenced by prazosin treatment, indicating that the sympathetic nervous system exerts a significant impact on urine proteome. Eight significantly changed proteins were previously annotated as urinary candidate biomarkers. Angiotensinogen, haptoglobin, and beta-2 microglobulin, which were reported to be associated with blood pressure, were validated via Western blot. Prazosin is widely used in clinical practice; thus, these protein changes should be considered when studying corresponding diseases such as hypertension, post-traumatic stress disorder and benign prostatic hyperplasia. The related physiological activities of α1-receptors, controlling blood pressure and fear response might significantly affect the urine proteome and warrant further biomarker studies. PMID:27780262

  19. Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease.

    PubMed

    Katsouri, Loukia; Vizcaychipi, Marcela P; McArthur, Simon; Harrison, Ian; Suárez-Calvet, Marc; Lleo, Alberto; Lloyd, Dafydd G; Ma, Daqing; Sastre, Magdalena

    2013-04-01

    Noradrenergic deficits have been described in the hippocampus and the frontal cortex of Alzheimer's disease brains, which are secondary to locus coeruleus degeneration. Locus coeruleus is the brain stem nucleus responsible for synthesis of noradrenaline and from where all noradrenergic neurons project. In addition, it has been suggested that noradrenaline might play a role in modulating inflammatory responses in Alzheimer's disease. In this study we aimed to investigate the effect of various agonists and antagonists for adrenergic receptors on amyloid precursor protein processing. Among them, we found that prazosin, an α(1)-adrenoceptor antagonist, was able to reduce the generation of amyloid β in N2a cells. Treatment of transgenic APP23 mice with prazosin prevented memory deficits over time. Although prazosin did not influence amyloid plaque load, it induced astrocytic proliferation and increased the release of apolipoprotein E and anti-inflammatory cytokines. These findings suggest that chronic treatment with prazosin leads to an anti-inflammatory response with potential beneficial effects on cognitive performance.

  20. Effect of counterions on physicochemical properties of prazosin salts.

    PubMed

    Kumar, Lokesh; Meena, Chhuttan Lal; Pawar, Yogesh B; Wahlang, Banrida; Tikoo, Kulbhushan; Jain, Rahul; Bansal, Arvind K

    2013-03-01

    This study evaluated the effect of counterions on the physicochemical properties of prazosin salts. Salt forms of prazosin, namely, mesylate, besylate, tosylate, camsylate, oxalate, and maleate, were prepared and compared with the marketed anhydrous and polyhydrate forms of prazosin hydrochloride. Physicochemical characterization was performed in the order of crystallinity, hygroscopicity, solubility, and stability to select the optimal salt(s). Permeability study in Caco-2 cell lines and in vivo bioavailability study in rat model were investigated to ascertain their biopharmaceutical advantage. All salt forms were crystalline, nonhygroscopic (except the anhydrous hydrochloride salt), and had solubility in the range of 0.2 to 1.6 mg/ml. All salts were physically and chemically stable at 40°C/75% relative humidity, but degraded in UV-visible light, except the anhydrous hydrochloride salt. Prazosin mesylate was selected as the optimal salt, as it possessed higher solubility, permeability, and bioavailability, compared to the commercial hydrochloride salts. Hydrochloride salt is reported to have poor bioavailability that is partially attributed to its low solubility and extensive common-ion effect in the gastric region. Factors like hydrophilicity of the counterion, hydration state of the salt, and melting point of the salt contribute to the physicochemical properties of the salts. This study has implications in the selection of an optimal salt form for prazosin, which is suitable for further development.

  1. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    DTIC Science & Technology

    2012-06-01

    of Prazosin for Combat Trauma PTSD PRINCIPAL INVESTIGATOR: Murray Raskind, M.D...31 May 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD 5b. GRANT...controlled trial to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist, prazosin , for reducing trauma nightmares and sleep

  2. Systemic or intra-prelimbic cortex infusion of prazosin impairs fear memory reconsolidation.

    PubMed

    Do Monte, Fabricio H; Souza, Rimenez R; Wong, Ting T; Carobrez, Antonio de Padua

    2013-05-01

    The alpha-1 adrenergic antagonist prazosin has been used to alleviate the symptoms of PTSD, but the mechanism remains unclear. One possibility is that prazosin may disrupt fear memory reconsolidation, leading to attenuation of fear responses. To test this hypothesis, we administered a single systemic injection of prazosin during the reconsolidation of olfactory fear conditioning in rats. We found that a post-retrieval injection of prazosin disrupted subsequent retrieval of fear. Similarly, intra-prelimbic cortex infusion of prazosin during the reconsolidation period also disrupted subsequent retrieval of fear. These findings suggest that fear memory undergoes reconsolidation through activation of alpha-1 adrenergic receptors in the prelimbic cortex.

  3. Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin.

    PubMed

    Boehnlein, James K; Kinzie, J David

    2007-03-01

    This article reviews the neurobiologic rationale for and presents clinical guidance concerning the use of medications that reduce central nervous system noradrenergic activity in the treatment of intrusive symptoms of posttraumatic stress disorder. The authors reviewed neurobiological studies, nonclinical studies using animal models, clinical case reports, open-label drug studies, and blinded, placebo-controlled drug studies. This review of the basic science and clinical literature, and the authors' clinical experience with culturally and demographically diverse populations, indicate that clonidine and prazosin can play a useful role in treating sleep disturbance and hyperarousal in posttraumatic stress disorder, with minimal adverse effects and low financial cost.

  4. Temperature dependence of the interaction of prazosin with lipid Langmuir monolayers.

    PubMed

    Gzyl-Malcher, Barbara; Handzlik, Jadwiga; Klekowska, Ewelina

    2013-12-01

    The influence of temperature on membrane-prazosin interactions was studied. Prazosin, a quinazoline derivative of 2-furoylpiperazine, is a classic antihypertensive and antiarrhythmic drug. A mixed cholesterol/phospholipid monolayer at the water/air interface was employed as a simplified biomembrane model. Brewster angle microscopy (BAM) was used to visualize the monolayer morphology. It was found that prazosin penetrates Langmuir monolayers and modifies the interactions between membrane components, causing monolayer fluidization. An increase in temperature facilitates penetration of prazosin into the monolayers. Prazosin interacts preferentially with phosphatidylcholine and modifies the morphology of the condensed phase domains of DPPC. In the presence of prazosin, monolayers collapse at lower surface pressures. The difference between the collapse pressures of monolayers on water with and without prazosin increases with temperature.

  5. Low-Dose Prazosin Alone and in Combination with Propranolol or Naltrexone: Effects on Ethanol- and Sucrose-Seeking and Self-Administration in the P Rat

    PubMed Central

    Verplaetse, Terril L.; Czachowski, Cristine L.

    2015-01-01

    Rationale Evidence suggests that the noradrenergic system mediates ethanol-reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. Methods This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer-seeking and self-administration. Male alcohol-preferring (P) rats (n=20/experiment) were trained to complete a response requirement (RR) resulting in access to 1% sucrose (n=10) or 10% ethanol (n=10) for 20min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, 1.0 mg/kg; intraperitoneally (IP)) or prazosin in combination with propranolol (5 mg/kg (IP); Exp1) or in combination with naltrexone (0.03 mg/kg (subcutaneously (SC); Exp2). Results For Exp1, prazosin alone effectively decreased sucrose-seeking more than ethanol-seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol-seeking more than sucrose-seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp2, prazosin alone and naltrexone alone were effective in decreasing ethanol-seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol-seeking and consumption and sucrose intake, but not sucrose-seeking. Conclusions Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone, but also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers. PMID:25743758

  6. Optimal Treatment Strategy for a Tumor Model under Immune Suppression

    PubMed Central

    Kim, Kwang Su; Cho, Giphil; Jung, Il Hyo

    2014-01-01

    We propose a mathematical model describing tumor-immune interactions under immune suppression. These days evidences indicate that the immune suppression related to cancer contributes to its progression. The mathematical model for tumor-immune interactions would provide a new methodology for more sophisticated treatment options of cancer. To do this we have developed a system of 11 ordinary differential equations including the movement, interaction, and activation of NK cells, CD8+T-cells, CD4+T cells, regulatory T cells, and dendritic cells under the presence of tumor and cytokines and the immune interactions. In addition, we apply two control therapies, immunotherapy and chemotherapy to the model in order to control growth of tumor. Using optimal control theory and numerical simulations, we obtain appropriate treatment strategies according to the ratio of the cost for two therapies, which suggest an optimal timing of each administration for the two types of models, without and with immunosuppressive effects. These results mean that the immune suppression can have an influence on treatment strategies for cancer. PMID:25140193

  7. Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis of Prazosin Trials.

    PubMed

    De Berardis, Domenico; Marini, Stefano; Serroni, Nicola; Iasevoli, Felice; Tomasetti, Carmine; de Bartolomeis, Andrea; Mazza, Monica; Tempesta, Daniela; Valchera, Alessandro; Fornaro, Michele; Pompili, Maurizio; Sepede, Gianna; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may deal with diverse health problems compared with civilians, they have a greater risk for psychiatric disorders, including PTSD, than civilians, even if the disorder may be also frequent in the general population. PTSD is associated with significant comorbidity, especially with mood disorders and substance abuse. Moreover, the suicide risk is higher in PTSD patients than in the general population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical antipsychotics and benzodiazepines are commonly employed in the management of PTSD, but often these treatments fail or are discontinued due to adverse effects. It has been demonstrated that high noradrenergic activity may be associated with hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably through the stimulation of α -1 adrenergic receptors in the brain prefrontal cortex. The α -1 adrenoreceptor antagonist prazosin decreases noradrenaline effects at brain α-1 adrenoreceptors and may be a promising agent in the treatment of PTSD, as some studies have found it effective and well tolerated. Therefore, the present review is aimed to examine the role of noradrenergic system in the pathophysiology of PTSD. Moreover, we conducted a systematic review to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta-analysis was used to combine data from multiple studies and better estimate the effect of prazosin on specific outcomes. We found prazosin to be significantly more efficacious than placebo in reducing distressing dreams in PTSD patients, even though our results should be interpreted with caution due to the small number of studies included in our quantitative synthesis.

  8. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    DTIC Science & Technology

    2011-06-01

    08-2-0069 TITLE: A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD PRINCIPAL INVESTIGATOR: Murray...2011Annual01-06-2011 A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD Murray Raskind Seattle Institute for Biomedical/Clinical...and tolerability of the alpha-1 adrenergic antagonist, prazosin , for reducing trauma nightmares and sleep disturbance and improving global

  9. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    DTIC Science & Technology

    2009-06-01

    of Prazosin for Combat Trauma PTSD PRINCIPAL INVESTIGATOR: Murray Raskind, M.D. Elaine Peskind, M.D. Kris Peterson...2008 – 31 May 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD 5b...group, randomized placebo controlled trial to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist, prazosin , for reducing trauma

  10. Molecular features of the prazosin molecule required for activation of Transport-P.

    PubMed

    da Silva, Joaquim Fernando Mendes; Walters, Marcus; Al-Damluji, Saad; Ganellin, C Robin

    2008-08-01

    Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.

  11. [Suppression of cycling activity in sheep using parenteral progestagen treatment].

    PubMed

    Janett, F; Camponovo, L; Lanker, U; Hässig, M; Thun, R

    2004-03-01

    The objective of this study was to evaluate the effect of two synthetic progestagen preparations Chlormadinone acetate (CAP, Chronosyn, Veterinaria AG Zürich) and Medroxyprogesterone acetate (MPA, Nadigest, G Streuli & Co. Uznach) on cycling activity and fertility in sheep. A flock of 28 non pregnant white alpine sheep was randomly divided into three groups, A (n = 10), B (n = 9) and C (n = 9). During a period of 4 weeks the cycling activity was confirmed by blood progesterone analysis. Thereafter, the animals of group A were treated with 50 mg CAP, those of group B with 140 mg MPA and those of group C with physiological saline solution. All injections were given intramuscularly. Suppression of endogenous progesterone secretion lasted from 28 to 49 days (mean = 39 days) in group A and from 42 to 70 days (mean = 50 days) in group B. The synchronization effect of both preparations was unsatisfactory as the occurrence of first estrus was distributed over a period of 3 weeks in group A and 4 weeks in group B. These findings could also be confirmed by the lambing period which lasted 52 days in group A and 36 days in group B. Control animals lambed within 9 days due to the synchronizing effect of the ram. The first fertile estrus was observed 36 days (group A) and 45 days (group B) after the treatment. In group A all 10 animals and in groups B and C 8 of 9 ewes each became pregnant. Parenteral progestagen application with CAP and MPA is a simple, safe and reversible method of estrus suppression in the sheep. The minimal suppressive duration of 4 (CAP) and 5 weeks (MPA) is not sufficient when a period of 3 months (alpine pasture period) is desired.

  12. High-performance liquid chromatography using electrochemical detection for the determination of prazosin in biological samples.

    PubMed

    Rathinavelu, A; Malave, A

    1995-08-04

    For the quantitation of prazosin a sensitive high-performance liquid chromatographic (HPLC) method was developed. This HPLC analysis method uses an electrochemical detection technique for the identification and quantitation of prazosin. In this assay the serum samples were deproteinized by using a simple acetonitrile precipitation technique that was followed by n-hexane extraction. Prazosin in the deproteinized serum sample was separated by an isocratic elution with an ODS Hypersil HPLC column (150 x 4.6 mm) using a mobile phase consisting of 0.05 M Na2HPO4-acetonitrile (60:40), pH 8.4. Prazosin that was eluted from the column was detected using a Coulochem II electrochemical detector. The precision of this assay method was assessed by performing inter- and intra-assay analyses by spiking prazosin free fetal bovine serum samples with 20 and 40 ng/ml concentrations of prazosin. In the intra-assay the recovery was 95.40 +/- 4.82% and 97.80 +/- 3.40%, respectively, for 20 and 40 ng/ml concentrations of prazosin that were used to spike the serum samples. This electrochemical detection HPLC assay method could be very useful in monitoring plasma levels of prazosin.

  13. Prazosin displays anticancer activity against human prostate cancers: targeting DNA and cell cycle.

    PubMed

    Lin, Ssu-Chia; Chueh, Shih-Chieh; Hsiao, Che-Jen; Li, Tsia-Kun; Chen, Tzu-Hsuan; Liao, Cho-Hwa; Lyu, Ping-Chiang; Guh, Jih-Hwa

    2007-10-01

    Quinazoline-based alpha1-adrenoceptor antagonists, in particular doxazosin and terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other alpha1-blockers, including doxazosin, terazosin, tamsulosin, and phentolamine. Prazosin induced G2 checkpoint arrest and subsequent apoptosis in prostate cancer PC-3, DU-145, and LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA strand breaks and ATM/ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25c phosphorylation at Ser216, nuclear export of Cdc25c, and cyclin-dependent kinase (Cdk) 1 phosphorylation at Tyr15. The data, together with sustained elevated cyclin A levels (other than cyclin B1 levels), suggested that Cdk1 activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated and caspase-executed apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdk1 inactivation and G2 checkpoint arrest. Subsequently, mitochondria-mediated caspase cascades are triggered to induce apoptosis in PC-3 cells.

  14. A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance

    DTIC Science & Technology

    2007-03-01

    AD_________________ Award Number: W81XWH-06-1-0014 TITLE: A Placebo-Controlled Trial of Prazosin ...06 – 22 Feb 07 4. TITLE AND SUBTITLE A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced 5a...adrenergic antagonist prazosin compared to placebo for combat trauma-related nightmares, sleep disturbance and overall function in recently combat

  15. Metabolism of prazosin in rat and characterization of metabolites in plasma, urine, faeces, brain and bile using liquid chromatography/mass spectrometry (LC/MS).

    PubMed

    Erve, J C L; Vashishtha, S C; Ojewoye, O; Adedoyin, A; Espina, R; Demaio, W; Talaat, R E

    2008-05-01

    1. Prazosin, 2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline, is an antihypertensive agent that has been used safely since 1976 and is currently being investigated for the treatment of post-traumatic stress disorder. The in vivo metabolism of prazosin in rat was first reported in 1977, although at the time analytical techniques were not as sophisticated, nor were the mass spectrometers as sensitive, as today. Recently, the in vitro metabolism of prazosin in rat liver microsomes and cryopreserved hepatocytes was investigated using liquid chromatography/mass spectrometry (LC/MS), which revealed new metabolic pathways. 2. In the present work, rat in vivo metabolism was reinvestigated using a quadrupole time-of-flight mass spectrometer coupled with ultra-performance liquid chromatography, or chip-based nanoflow electrospray ionization, with the aim of identifying metabolites revealed by the in vitro studies and any new metabolites. 3. It is reported that prazosin was metabolized in rats to produce the metabolites observed in vitro. In addition, new phase I metabolites, M18, M20 and M21, were formed and conjugation with glucose or taurine formed the new phase II metabolites, M16 and M19, respectively. 4. Evidence for bioactivation of prazosin included detection of ring-opened metabolites (M4 and M7) and a cysteinyl-glycine conjugate (M17). Further support to the structure of the ring-opened metabolite M7 was obtained by nuclear magnetic resonance (NMR) experiments on M7 isolated from urine.

  16. Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats.

    PubMed

    Kristek, F; Koprdova, R

    2011-06-01

    The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.

  17. Prazosin for Treatment With PTSD And Comorbid Alcohol Dependence

    DTIC Science & Technology

    2010-07-01

    There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with...AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with...sleep disturbance in combat veterans with PTSD and alcohol dependence . The objective of this study is to evaluate the efficacy of prazosis (16mg

  18. Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin.

    PubMed

    Thomas, Dierk; Wimmer, Anna-Britt; Wu, Kezhong; Hammerling, Bettina C; Ficker, Eckhard K; Kuryshev, Yuri A; Kiehn, Johann; Katus, Hugo A; Schoels, Wolfgang; Karle, Christoph A

    2004-05-01

    Human ether-a-go-go-related gene (HERG) potassium channels are expressed in multiple tissues including the heart and adenocarcinomas. In cardiomyocytes, HERG encodes the alpha-subunit underlying the rapid component of the delayed rectifier potassium current, I(Kr), and pharmacological reduction of HERG currents may cause acquired long QT syndrome. In addition, HERG currents have been shown to be involved in the regulation of cell proliferation and apoptosis. Selective alpha 1-adrenoceptor antagonists are commonly used in the treatment of hypertension and benign prostatic hyperplasia. Recently, doxazosin has been associated with an increased risk of heart failure. Moreover, quinazoline-derived alpha 1-inhibitors induce apoptosis in cardiomyocytes and prostate tumor cells independently of alpha1-adrenoceptor blockade. To assess the action of the effects of prazosin, doxazosin, and terazosin on HERG currents, we investigated their acute electrophysiological effects on cloned HERG potassium channels heterologously expressed in Xenopus oocytes and HEK 293 cells.Prazosin, doxazosin, and terazosin blocked HERG currents in Xenopus oocytes with IC(50) values of 10.1, 18.2, and 113.2 microM respectively, whereas the IC(50) values for HERG channel inhibition in human HEK 293 cells were 1.57 microM, 585.1 nM, and 17.7 microM. Detailed biophysical studies revealed that inhibition by the prototype alpha 1-blocker prazosin occurred in closed, open, and inactivated channels. Analysis of the voltage-dependence of block displayed a reduction of inhibition at positive membrane potentials. Frequency-dependence was not observed. Prazosin caused a negative shift in the voltage-dependence of both activation (-3.8 mV) and inactivation (-9.4 mV). The S6 mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) HERG current blockade, indicating that prazosin binds to a common drug receptor within the pore-S6 region. In conclusion, this study demonstrates that HERG

  19. Interaction of prazosin with model membranes--a Langmuir monolayer study.

    PubMed

    Gzyl-Malcher, Barbara; Handzlik, Jadwiga; Klekowska, Ewelina

    2012-10-01

    In this study, the effect of prazosin on the molecular interactions between cholesterol and 1,2-dipalmitoylphosphatidylcholine (DPPC) within a monolayer at an air-water interface was studied. A mixed cholesterol/DPPC monolayer was employed as a model lipid membrane. From a detailed analysis of surface pressure-area isotherms, it was concluded that DPPC and cholesterol were miscible and formed non-ideal monolayers on prazosin solution. The thermodynamic stability of the mixed monolayers was investigated by analyzing the free energy of mixing. It was found that the mixed monolayers were more stable than the single component monolayers. Monolayers spread over a subphase with prazosin were more compressible than those spread on pure water. To quantify the effect of prazosin on the monolayer stability, the Gibbs free energy due to the presence of prazosin in the water subphase was calculated. It was found that prazosin penetrated and destabilized mixed cholesterol/DPPC monolayers. However, a comparison of the drug penetration into the pure DPPC monolayer and the mixed cholesterol/DPPC monolayer showed that the presence of cholesterol in the DPPC monolayer considerably restricted the drug penetration.

  20. A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance

    DTIC Science & Technology

    2008-03-01

    AD_________________ Award Number: W81XWH-06-2-0014 TITLE: A Placebo-Controlled Trial of Prazosin ...CONTRACT NUMBER A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance 5b. GRANT...proposal is to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist prazosin compared to placebo for combat trauma-related

  1. A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance

    DTIC Science & Technology

    2009-03-01

    AD_________________ Award Number: W81XWH-06-2-0014 TITLE: A Placebo-Controlled Trial of Prazosin ...CONTRACT NUMBER A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance 5b. GRANT NUMBER...proposal is to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist prazosin compared to placebo for combat trauma-related

  2. Quiet engine program: Turbine noise suppression. -Volume 1: General treatment evaluation and measurement techniques

    NASA Technical Reports Server (NTRS)

    Clemons, A.; Hehmann, H.; Radecki, K.

    1973-01-01

    Acoustic treatment was developed for jet engine turbine noise suppression. Acoustic impedance and duct transmission loss measurements were made for various suppression systems. An environmental compatibility study on several material types having suppression characteristics is presented. Two sets of engine hardware were designed and are described along with engine test results which include probe, farfield, near field, and acoustic directional array data. Comparisons of the expected and the measured suppression levels are given as well as a discussion of test results and design techniques.

  3. Pharmacology of appetite suppression: implication for the treatment of obesity.

    PubMed

    Halford, J C

    2001-12-01

    Given the current global epidemic of obesity there is a demand for new anti-obesity drugs to overcome the problem. Many pharmacological agents reduce food intake and significantly decrease body mass when administered to animals but affect feeding behaviour in a profoundly different way indicating the variety of biological mechanisms by which such agents act (appetite verses non-appetite). More limited clinical data demonstrates that some of the same drugs produce decreases in food intake and weight loss in humans. A few of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). These drugs that modify the daily flux of appetite could be considered as 'appetite suppressants' with clinical potential as anti-obesity agents. Drugs that can be considered suitable candidates for appetite suppressants are agents that enhance peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin, CART and Melanocortins) or monoamine neurotransmitters (such as serotonin, nor-adrenaline and possibly dopamine). Recently, the hormone leptin has become regarded as a key hormonal signal linking adipose tissue status with a number of key central nervous system circuits (NPY, CART, CRF, Melanocortins and possibly Orexins). This tonic system may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i) psychological experience and behavioural expression of appetite, (ii) metabolism and peripheral physiology, and (iii) functioning of CNS neural pathways. In humans, such modulation of appetite will involve changes in total caloric consumption, subjective changes in feelings of hunger and fullness, preferences for specific food items, and general macronutrient preferences. These may be

  4. Voltammetric and spectrophotometric techniques for the determination of the antihypertensive drug Prazosin in urine and formulations.

    PubMed

    Arranz, A; de Betoño, S F; Echevarria, C; Moreda, J M; Cid, A; Valentín, J F

    1999-12-01

    A sensitive method was developed to determine Prazosin using a nafion modified carbon paste electrode (NMCPE). Prazosin was accumulated at a potential of 750 mV in Britton-Robinson buffer (pH 6.0) and then a negative sweep was made obtaining a cathodic peak close to 0 V. Cyclic voltammetric studies indicated that the process was quasi-reversible, and fundamentally controlled by adsorption. To obtain a good sensitivity, the instrumental and accumulation variables were studied using differential pulse voltammetry (DPV). Adsorptive voltammetric peak currents showed a linear response for Prazosin concentrations in the range between 4.0 x 10(-11) and 4.0 x 10(-8) M with two different slopes, and a detection limit (LOD) of 3.1 x 10(-11)M was obtained. The variation coefficient (CV) for a 8.0 x 10(-10) M solution (n = 10) was 4.08%. A spectrophotometric study of Prazosin was also carried out and two absorption bands were obtained at 246 and 329 nm (pH 1.8). The band at 329 nm was pH-dependent and its height and position changed with the pH values, so this allowed the pK'a determination (7.14 +/- 0.20) using different methods. The detection limit reached by means of UV-spectrophotometry was 0.9 x 10(-7) M, and the variation coefficient for 1.5 x 10(-5) M Prazosin solutions was 1.14% (n = 10). Although the sensitivity of the UV-spectrophotometric method was lower than that obtained using adsorptive stripping-differential pulse voltammetry (AdS-DPV), it could be applied to the determination of Prazosin in Minipres tablets. The voltammetric method was used for the determination of the drug in human urine samples at trace levels with good recoveries.

  5. Binding of [3H]-prazosin and [3H]-dihydroergocryptine to rat cardiac alpha-adrenoceptors.

    PubMed Central

    Guicheney, P.; Meyer, P.

    1981-01-01

    1 [3H]-prazosin binds specifically to a single class of alpha-adrenoceptors in rat cardiac membranes (KD25 degrees C = 0.2 nM). 2 That these receptors are of the alpha 1-type was indicated by competition studies, i.e. alpha 1-antagonists such as prazosin and (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1, 4-benzodioxane (WB 4101) were more potent than the alpha 2-antagonists, yohimbine and piperoxan in inhibiting [3H]-prazosin binding. 3 A comparative study of [3H]-prazosin binding and [3H]-dihydroergocryptine binding to cardiac membranes showed that both [3H]-prazosin and [3H]-dihydroergocryptine (at low concentrations) bind to alpha 2-adrenoceptors, while [3H]-dihydroergocryptine (at higher concentrations) also binds to another class of sites. PMID:6269682

  6. Effects of modafinil and prazosin on cognitive and physiological functions in healthy volunteers.

    PubMed

    Winder-Rhodes, S E; Chamberlain, S R; Idris, M I; Robbins, T W; Sahakian, B J; Müller, U

    2010-11-01

    Previous research has demonstrated cognitive-enhancing effects of modafinil in humans and generated evidence for its therapeutic potential in psychiatric disorders. The neurochemical basis of these effects remains unresolved although a role for α1-adrenoceptors has been hypothesised. In this within-subject, double-blind, placebo-controlled study, 12 healthy male adults received modafinil (300 mg), the α1-adrenoceptor antagonist prazosin (3 mg), both together and placebo on separate occasions at least 5 days apart. Cognitive effects were assessed using a well-validated testing battery focusing on executive and working memory functions. Blood pressure, heart rate and salivary α-amylase (sAA) were measured at hourly intervals. Cognitive effects of modafinil and prazosin were identified at the difficult levels of the One-Touch Stockings of Cambridge (OTSOC) planning task. Prazosin antagonized the error-reducing effect of modafinil when the agents were given together. In contrast, the combined agents acted synergistically to increase time taken to complete OTSOC problems compared with placebo. The tachycardic and sAA-elevating effects of prazosin were also potentiated by concurrent modafinil administration. The current data suggest that the cognitive effects of modafinil on performance accuracy and latency are dissociable in terms of their neurochemical mechanisms. Our findings support the hypothesised involvement of α1-adrenoceptors in some of the cognitive-enhancing effects of modafinil and warrant further investigation.

  7. The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway.

    PubMed

    Assad Kahn, Suzana; Costa, Silvia Lima; Gholamin, Sharareh; Nitta, Ryan T; Dubois, Luiz Gustavo; Fève, Marie; Zeniou, Maria; Coelho, Paulo Lucas Cerqueira; El-Habr, Elias; Cadusseau, Josette; Varlet, Pascale; Mitra, Siddhartha S; Devaux, Bertrand; Kilhoffer, Marie-Claude; Cheshier, Samuel H; Moura-Neto, Vivaldo; Haiech, Jacques; Junier, Marie-Pierre; Chneiweiss, Hervé

    2016-05-01

    A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an α1- and α2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKCδ-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKCδ activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hypertension, inhibits glioblastoma growth through a PKCδ-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients.

  8. High therapeutic concentration of prazosin up-regulates angiogenic IL6 and CCL2 genes in hepatocellular carcinoma cells.

    PubMed

    Lin, Zu-Yau; Chuang, Wan-Long

    2012-12-01

    Alteration of the oxidative stress of hepatocellular carcinoma (HCC) cells can influence the expressions of genes favored angiogenesis. Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3. Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3. This study was to investigate the influence of therapeutic concentrations of prazosin (0.01 and 0.1μM) on cell proliferation and differential expressions of CCL2, CCL20, CXCL6, CXCL10, IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines. Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were investigated by 0.01 and 0.1μM prazosin. The premixed WST-1 cell proliferation reagent was applied for proliferation assay. Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines. Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes. However, 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion, high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress. Clinical application of prazosin in patients with HCC should consider this possibility.

  9. Suppression of surface crystallization on borosilicate glass using RF plasma treatment

    NASA Astrophysics Data System (ADS)

    Yoo, Sunghyun; Ji, Chang-Hyeon; Jin, Joo-Young; Kim, Yong-Kweon

    2014-10-01

    Surface crystallization on a commercial grade borosilicate glass wafer, Borofloat® 33, is effectively prevented against 3 h of thermal reflow process at 850 °C. Surface plasma treatment with three different reactive gases, CF4, SF6, and Cl2, has been performed prior to the annealing. The effect of plasma treatment on surface ion concentration and nucleation of cristobalite were examined through optical microscope and x-ray photoemission spectroscopy. The dominant cause that suppresses crystallization was verified to be the increase of surface ion concentration of alumina during the plasma treatment. Both CF4 and SF6 treatment of no less than 30 s showed significant efficacy in suppressing crystallization by a factor of more than 112. Average surface roughness and the optical transparency were also enhanced by a factor of 15 and 3, respectively, compared to untreated sample.

  10. Dopamine receptor D3 regulates endocytic sorting by a Prazosin-sensitive interaction with the coatomer COPI.

    PubMed

    Zhang, Xin; Wang, Wenchao; Bedigian, Anne V; Coughlin, Margaret L; Mitchison, Timothy J; Eggert, Ulrike S

    2012-07-31

    Macromolecules enter cells by endocytosis and are sorted to different cellular destinations in early/sorting endosomes. The mechanism and regulation of sorting are poorly understood, although transitions between vesicular and tubular endosomes are important. We found that the antihypertensive drug Prazosin inhibits endocytic sorting by an off-target perturbation of the G protein-coupled receptor dopamine receptor D(3) (DRD3). Prazosin is also a potent cytokinesis inhibitor, likely as a consequence of its effects on endosomes. Prazosin stabilizes a normally transient interaction between DRD3 and the coatomer COPI, a complex involved in membrane transport, and shifts endosomal morphology entirely to tubules, disrupting cargo sorting. RNAi depletion of DRD3 alone also inhibits endocytic sorting, indicating a noncanonical role for a G protein-coupled receptor. Prazosin is a powerful tool for rapid and reversible perturbation of endocytic dynamics.

  11. Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression

    SciTech Connect

    Kotzin, B.L.; Arndt, R.; Okada, S.; Ward, R.; Thach, A.B.; Strober, S.

    1986-05-01

    We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.

  12. Antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats.

    PubMed

    Murahata, Yusuke; Yamamoto, Asami; Miki, Yuya; Hikasa, Yoshiaki

    2014-03-01

    This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 40 µg/kg medetomidine intramuscularly and saline (as the control), 160 µg/kg prazosin, or 40, 160 or 480 µg/kg atipamezole or yohimbine intravenously 0.5 hr later. Volume, pH and specific gravity of urine; plasma arginine vasopressin (AVP) level; and creatinine, osmolality and electrolyte levels in both urine and plasma were measured. Both atipamezole and yohimbine, but not prazosin, antagonized medetomidine-induced diuresis. The antidiuretic effect of atipamezole was more potent than that of yohimbine, but was not dose dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed medetomidine-induced decreases in both urine specific gravity and osmolality and increases in plasma osmolality and free-water clearance. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP level, although the highest dose of both atipamezole and yohimbine initially and temporarily increased plasma AVP levels, suggesting that this may partly influence the antidiuretic effects of both agents. The diuretic effect of medetomidine in cats may be mediated by α2-adrenoceptors, but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against medetomidine-induced diuresis in healthy cats.

  13. Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants.

    PubMed

    Shaw, W N

    1993-11-01

    LY255582, administered subcutaneously, decreased food intake and body weight gain of fed obese Zucker rats during the entire 30-day period of treatment. No tolerance to these biologic effects of LY255582 could be demonstrated. d-Amphetamine and naltrexone, administered subcutaneously, and d,l-fenfluramine and salbutamol, administered orally, decreased food intake for no more than 6 to 12 days, in contrast to the long-lasting effects of LY255582. Salbutamol suppressed the appetite of obese rats for 3-4 days only. After an additional 12 days of treatment, weight gain decreased significantly accompanied by no appetite suppression. Thus, there is a difference in the duration of action of the opioid antagonist, LY255582, when compared to amphetamine, fenfluramine, naltrexone, and salbutamol, on food intake and body weight gain of obese rats.

  14. Novel Burst Suppression Segmentation in the Joint Time-Frequency Domain for EEG in Treatment of Status Epilepticus

    PubMed Central

    Lee, Jaeyun; Song, Woo-Jin; Lee, Hyang Woon

    2016-01-01

    We developed a method to distinguish bursts and suppressions for EEG burst suppression from the treatments of status epilepticus, employing the joint time-frequency domain. We obtained the feature used in the proposed method from the joint use of the time and frequency domains, and we estimated the decision as to whether the measured EEG was a burst segment or suppression segment by the maximum likelihood estimation. We evaluated the performance of the proposed method in terms of its accordance with the visual scores and estimation of the burst suppression ratio. The accuracy was higher than the sole use of the time or frequency domains, as well as conventional methods conducted in the time domain. In addition, probabilistic modeling provided a more simplified optimization than conventional methods. Burst suppression quantification necessitated precise burst suppression segmentation with an easy optimization; therefore, the excellent discrimination and the easy optimization of burst suppression by the proposed method appear to be beneficial. PMID:27872655

  15. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    1999-12-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis.

  16. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment

    PubMed Central

    Im, Sin-Hyeog; Barchan, Dora; Fuchs, Sara; Souroujon, Miriam C.

    1999-01-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR α-subunit (Hα1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Hα1-205–induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. J. Clin. Invest. 104:1723–1730 (1999). PMID:10606626

  17. Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma.

    PubMed Central

    Samojlik, E; Veldhuis, J D; Wells, S A; Santen, R J

    1980-01-01

    We evaluated the comparative effects of aminoglutethimide (AG) on androgen and estrogen levels estrone ([E1], estradiol [E2], plasma dehydroepiandrosterone-sulfate [DHEA-S], testosterone [T], dihydrotestosterone [DHT], delta 4-androstenedione [delta 4-A]), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin in postmenopausal patients with breast cancer randomly allocated to either AG treatment or bilateral surgical adrenalectomy as a control group. In response to either treatment, the plasma levels of E1 fell 62-75% (P less than 0.001) and urine E1 85.7-88.7% (P less than 0.001) in all study days over a 12-wk period. Similarly, the concentrations of E2 in plasma and urine fell 40-72% without statistically significant differences between the two treatment modalities. The relatively weak androgen, DHEA-S, was reduced by 92% (877.3 +/- 184.6 to 71.8 +/- 14.5 ng/ml) at 12 wk in women treated with AG, but suppressed nearly 99% (1,151 +/- 262 to 5.8 +/- 3.3 ng/ml) in adrenalectomized women. At all time points after treatment, the DHEA-S levels were significantly higher in patients receiving AG. Plasma concentrations of the potent androgens, T and DHT, were also relatively preserved during AG treatment. T levels were never significantly reduced by AG, and DHT concentrations were decreased only at the 4th wk to a maximum of 20%. delta 4-A levels fell 56% in response to this drug only on the 12th wk of therapy (basal, 0.79 +/- 0.09 ng/ml; 12 wk, 0.35 +/- 0.07 ng/ml). In marked contrast, all androgens fell significantly at each time period in response to surgical adrenalectomy, with an 81% maximum suppression of T, 73% of DHT, and 97% of delta 4-A. In response to estrogen suppression, plasma levels of FSH, LH, and prolactin did not change significantly throughout the treatment period in either therapy group. To examine possible contributions of the postmenopausal ovary to hormone levels during therapy, data from surgically castrate and spontaneously

  18. Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment

    PubMed Central

    Lauriola, Mattia; Enuka, Yehoshua; Zeisel, Amit; D’Uva, Gabriele; Roth, Lee; Sharon-Sevilla, Michal; Lindzen, Moshit; Sharma, Kirti; Nevo, Nava; Feldman, Morris; Carvalho, Silvia; Cohen-Dvashi, Hadas; Kedmi, Merav; Ben-Chetrit, Nir; Chen, Alon; Solmi, Rossella; Wiemann, Stefan; Schmitt, Fernando; Domany, Eytan; Yarden, Yosef

    2014-01-01

    Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR’s positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR’s feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy. PMID:25278152

  19. Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides.

    PubMed

    Ladenheim, Ellen E; Knipp, Susan

    2007-05-16

    Peripheral administration of bombesin (BN) and the related mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), suppress food intake in rats. To examine whether all BN-like peptides utilize the same neural pathways to reduce feeding, rats were treated on postnatal day 2 with the injection vehicle or capsaicin, a neurotoxin that damages a subset of visceral afferent fibers. When rats reached adulthood, we compared the ability of a dose range of systemically administered BN, GRP18-27 and NMB to reduce intake of a 0.5 kcal/ml glucose solution in a short-term feeding test. Our results demonstrate that capsaicin treatment abolished or attenuated the suppression of glucose intake produced by BN and NMB but had no effect on the ability of GRP to reduce feeding. These results suggest that different neural substrates underlie the anorexic effects of peripherally administered BN-like peptides.

  20. Malonic acid suppresses mucin-type O-glycan degradation during hydrazine treatment of glycoproteins.

    PubMed

    Goso, Yukinobu

    2016-03-01

    Hydrazine treatment is frequently used for releasing mucin-type O-glycans (O-glycans) from glycoproteins because the method provides O-glycans that retain a reducible GalNAc at their reducing end, which is available for fluorescent labeling. However, many O-glycans are degraded by "peeling" during this treatment. In the current study, it was found that malonic acid suppressed O-glycan degradation during hydrazine treatment of bovine fetuin or porcine gastric mucin in both the gas and liquid phases. This is paradoxical because the release of O-glycans from glycoproteins occurs under alkaline conditions. However, malonic acid seems to prevent the degradation through its acidic property given that other weak acids also prevented the degradation. Accordingly, disodium malonate did not suppress O-glycan degradation. Application of this method to rat gastric mucin demonstrated that the majority of the major O-glycans obtained in the presence of malonic acid were intact, whereas those obtained in the absence of malonic acid were degraded. These results suggest that hydrazine treatment in the presence of malonic acid would allow glycomic analysis of native mucin glycoproteins.

  1. The alpha1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration.

    PubMed

    Greenwell, Thomas N; Walker, Brendan M; Cottone, Pietro; Zorrilla, Eric P; Koob, George F

    2009-01-01

    Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin, an alpha1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus, prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data suggest that the alpha1 adrenergic system may contribute to mechanisms that promote dependence in rats with extended access.

  2. Time-dependent effects of prazosin on the development of methamphetamine conditioned hyperactivity and context-specific sensitization in mice.

    PubMed

    White, André O; Rauhut, Anthony S

    2014-04-15

    The present experiments examined the effects of prazosin, a selective α₁-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 min prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 h (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-h delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α₁-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes.

  3. Antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats

    PubMed Central

    Murahata, Yusuke; Miki, Yuya; Hikasa, Yoshiaki

    2014-01-01

    This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α2-adrenoceptors but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats. PMID:25356000

  4. Antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats.

    PubMed

    Murahata, Yusuke; Miki, Yuya; Hikasa, Yoshiaki

    2014-10-01

    This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α2-adrenoceptors but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.

  5. Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC.

    PubMed

    Li, Rong; Zhang, Yujuan; Zheng, Xiufen; Peng, Shanshan; Yuan, Keng; Zhang, Xusheng; Min, Weiping

    2017-02-23

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC.

  6. Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC

    PubMed Central

    Li, Rong; Zhang, Yujuan; Zheng, Xiufen; Peng, Shanshan; Yuan, Keng; Zhang, Xusheng; Min, Weiping

    2017-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC. PMID:28230210

  7. Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice.

    PubMed

    Luo, Xinjing; Zuo, Xiaoxia; Mo, Xuanrong; Zhou, Yaou; Xiao, Xianzhong

    2011-10-01

    Although the level of heat shock protein (Hsp72) has been shown to be enhanced in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid, it remains unclear what role extracellular Hsp72 plays in the pathogenesis of RA. This study was conducted to investigate the effects of recombinant human Hsp72 on collagen-induced arthritis (CIA) when administered therapeutically and elucidate its underlying mechanism. We demonstrated that recombinant Hsp72 significantly reduced disease severity. Hsp72-treated animals displayed significantly less cartilage and bone destruction than that in the controls. Hsp72 treatment also reduced the expression of tumor necrosis factor alpha and interleukin 6 in the sera. Furthermore, Hsp72 treatment significantly inhibited activation of nuclear factor kappa B (NF-κB) in synovial tissues of CIA mice. These findings suggest that recombinant Hsp72 effectively suppressed synovial inflammation and the development and progress of CIA, which is mediated through the reduction of production of proinflammatory cytokines and the suppression of activation of NF-κB pathway.

  8. Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Z.; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

    2016-03-01

    We introduce photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage in synchrony with photo-initiation of tumor-confined, multikinase inhibitor release. The PMIL is a biodegradable delivery system comprised of a nanoliposome carrying a photoactivable chromophore (benzoporphyrin derivative monoacid A, BPD) in its bilayer. A multikinase inhibitor-loaded PEG-PLGA nanoparticle is encapsulated within the liposome, which acts a barrier to nanoparticle erosion and drug release. Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates tumor-confined drug release from the nanoparticle. This talk presents promising preclinical data in mouse models of pancreatic cancer utilizing this concept to suppress the VEGF and MET signaling pathways—both critical to cancer progression, metastasis and treatment escape. A single PMIL treatment using low doses of a multikanse inhibitor (cabozantinib, XL184) achieves sustained tumor reduction and suppresses metastatic escape, whereas combination therapy by co-administration of the individual agents has significantly reduced efficacy. The PMIL concept is amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies whilst reducing systemic drug exposure and associated toxicities.

  9. Use and abuse of appetite-suppressant drugs in the treatment of obesity.

    PubMed

    Bray, G A

    1993-10-01

    Most of the available appetite-suppressant drugs act on noradrenergic and possibly dopaminergic receptors to produce satiety. A smaller number increase excess neuronal serotonin levels by blocking serotonin reuptake or by increasing its release. All these drugs produce significantly greater weight loss than does placebo in most studies. Abuse is a problem with amphetamine, methamphetamine, and benzphetamine, whereas other drugs have minimal or no potential for abuse. Weight loss can be sustained for up to 36 months. Net weight loss, compared with placebo, ranges from 2 to 10 kg, and weight regain after terminating drug treatment proves that drugs do not work when not taken. The stigma of obesity, the public opprobrium toward obese persons, and regulatory rigidity have led to unjustified distrust in the potential of drug treatment for obesity.

  10. Molecular exploration of the α(1A)-adrenoceptor orthosteric site: binding site definition for epinephrine, HEAT and prazosin.

    PubMed

    Maïga, Arhamatoulaye; Dupont, Mélanie; Blanchet, Guillaume; Marcon, Elodie; Gilquin, Bernard; Servent, Denis; Gilles, Nicolas

    2014-12-20

    Despite the physiological and pharmacological importance of the α1A-adrenoreceptor, the mode of interactions of classical agonists and radioactive ligands with this receptor is not yet clearly defined. Here, we used mutagenesis studies and binding experiments to evaluate the importance of 11 receptor sites for the binding of (125)I-HEAT, (3)H-prazosin and epinephrine. Only one residue (F312) commonly interacts with the three molecules, and, surprisingly, D106 interacts only with epinephrine in a moderate way. Our docking model shows that prazosin and HEAT are almost superimposed into the orthosteric pocket with their tetralone and quinazoline rings close to the phenyl ring of the agonist.

  11. Treatment with FGFR2-IIIc monoclonal antibody suppresses weight gain and adiposity in KKAy mice

    PubMed Central

    Nonogaki, K; Kaji, T; Yamazaki, T; Murakami, Mari

    2016-01-01

    Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKAy mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.5 mg kg−1) significantly suppressed body weight gain and epididymal white adipose tissue weight in individually housed KKAy mice while having no effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody significantly increased plasma-free fatty acid levels while having no effect on blood glucose or plasma FGF21 levels. Moreover, treatment with FGFR2-IIIc antibody had no significant effect on the expression of uncoupling protein-1, uncoupling protein-2 or peroxisome proliferator-activated receptor-γ coactivator 1α in the epididymal white adipose tissue. The treatment with FGFR2-IIIc antibody had no significant effects on daily food intake and body weight gain in individually housed KK mice. These findings suggest that FGFR2-IIIc upregulates the adiposity induced by social isolation in KKAy mice, and that decreased expression and/or function of FGFR2c might be a compensatory response to enhanced adiposity. Inhibition of FGFR2-IIIc function might be a novel therapeutic approach for obesity. PMID:27892934

  12. Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage

    PubMed Central

    2012-01-01

    Background Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Methods Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. Results When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the

  13. Optimization of suppression for two-element treatment liners for turbomachinery exhaust ducts

    NASA Technical Reports Server (NTRS)

    Motsinger, R. E.; Kraft, R. E.; Zwick, J. W.; Vukelich, S. I.; Minner, G. L.; Baumeister, K. J.

    1976-01-01

    Sound wave propagation in a soft-walled rectangular duct with steady uniform flow was investigated at exhaust conditions, incorporating the solution equations for sound wave propagation in a rectangular duct with multiple longitudinal wall treatment segments. Modal analysis was employed to find the solution equations and to study the effectiveness of a uniform and of a two-sectional liner in attenuating sound power in a treated rectangular duct without flow (M = 0) and with uniform flow of Mach 0.3. Two-segment liners were shown to increase the attenuation of sound as compared to a uniform liner. The predicted sound attenuation was compared with measured laboratory results for an optimized two-segment suppressor. Good correlation was obtained between the measured and predicted suppressions when practical variations in the modal content and impedance were taken into account. Two parametric studies were also completed.

  14. The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

    PubMed

    Dettmar, P W; Little, S L; Baxter, T

    2005-01-01

    Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets.

  15. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    SciTech Connect

    Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

    2012-03-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  16. Examining the relative effects of fire weather, suppression and fuel treatment on fire behaviour--a simulation study.

    PubMed

    Penman, T D; Collins, L; Price, O F; Bradstock, R A; Metcalf, S; Chong, D M O

    2013-12-15

    Large budgets are spent on both suppression and fuel treatments in order to reduce the risk of wildfires. There is little evidence regarding the relative contribution of fire weather, suppression and fuel treatments in determining the risk posed from wildfires. Here we undertake a simulation study in the Sydney Basin, Australia, to examine this question using a fire behaviour model (Phoenix Rapidfire). Results of the study indicate that fire behaviour is most strongly influenced by fire weather. Suppression has a greater influence on whether a fire reaches 5 ha in size compared to fuel treatments. In contrast, fuel treatments have a stronger effect on the fire size and maximum distance the fire travels. The study suggests that fire management agencies will receive additional benefits from fuel treatment if they are located in areas which suppression resources can respond rapidly and attempt to contain the fires. No combination of treatments contained all fires, and the proportion of uncontained fires increased under more severe fire weather when the greatest number of properties are lost. Our study highlights the importance of alternative management strategies to reduce the risk of property loss.

  17. Facilitation of sodium intake by combining noradrenaline into the lateral parabrachial nucleus with prazosin peripherally.

    PubMed

    Gasparini, S; Gomide, J M C; Andrade-Franzé, G M F; Totola, L T; De Luca, L A; Colombari, D S A; De Paula, P M; Moreira, T S; Menani, J V

    2013-10-01

    Injections of noradrenaline into the lateral parabrachial nucleus (LPBN) increase arterial pressure and 1.8% NaCl intake and decrease water intake in rats treated with the diuretic furosemide (FURO) combined with a low dose of the angiotensin converting enzyme inhibitor captopril (CAP). In the present study, we investigated the influence of the pressor response elicited by noradrenaline injected into the LPBN on FURO+CAP-induced water and 1.8% NaCl intake. Male Holtzman rats with bilateral stainless steel guide-cannulas implanted into LPBN were used. Bilateral injections of noradrenaline (40 nmol/0.2 μl) into the LPBN increased FURO+CAP-induced 1.8% NaCl intake (12.2±3.5, vs., saline: 4.2±0.8 ml/180 min), reduced water intake and strongly increased arterial pressure (50±7, vs. saline: 1±1 mmHg). The blockade of the α1 adrenoceptors with the prazosin injected intraperitoneally abolished the pressor response and increased 1.8% NaCl and water intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. The deactivation of baro and perhaps volume receptors due to the cardiovascular effects of prazosin is a mechanism that may facilitate water and NaCl intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. Therefore, the activation of α2 adrenoceptors with noradrenaline injected into the LPBN, at least in dose tested, may not completely remove the inhibitory signals produced by the activation of the cardiovascular receptors, particularly the signals that result from the extra activation of these receptors with the increase of arterial pressure.

  18. Novel Americium Treatment Process for Surface Water and Dust Suppression Water

    SciTech Connect

    Tiepel, E.W.; Pigeon, P.; Nesta, S.; Anderson, J.

    2006-07-01

    -241 contaminated pond water, surface run-off and D and D dust suppression water during the later stages of the D and D effort at Rocky Flats. This novel chemical treatment system allowed for highly efficient, high-volume treatment of all contaminated waste waters to the very low stream standard of 0.15 pCi/1 with strict compliance to the RFCA discharge criteria for release to off-site surface waters. The rapid development and implementation of the treatment system avoided water management issues that would have had to be addressed if contaminated water had remained in Pond A-4 into the Spring of 2005. Implementation of this treatment system for the Pond A-4 waters and the D and D waters from Buildings 776 and 371 enabled the site to achieve cost-effective treatment that minimized secondary waste generation, avoiding the need for expensive off-site water disposal. Water treatment was conducted for a cost of less than $0.20/gal which included all development costs, capital costs and operational costs. This innovative and rapid response effort saved the RFETS cleanup program well in excess of $30 million for the potential cost of off-site transportation and treatment of radioactive liquid waste. (authors)

  19. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects.

    PubMed

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C

    2001-05-01

    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  20. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.

    PubMed

    Scheid, Johannes F; Horwitz, Joshua A; Bar-On, Yotam; Kreider, Edward F; Lu, Ching-Lan; Lorenzi, Julio C C; Feldmann, Anna; Braunschweig, Malte; Nogueira, Lilian; Oliveira, Thiago; Shimeliovich, Irina; Patel, Roshni; Burke, Leah; Cohen, Yehuda Z; Hadrigan, Sonya; Settler, Allison; Witmer-Pack, Maggi; West, Anthony P; Juelg, Boris; Keler, Tibor; Hawthorne, Thomas; Zingman, Barry; Gulick, Roy M; Pfeifer, Nico; Learn, Gerald H; Seaman, Michael S; Bjorkman, Pamela J; Klein, Florian; Schlesinger, Sarah J; Walker, Bruce D; Hahn, Beatrice H; Nussenzweig, Michel C

    2016-07-28

    Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

  1. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption

    PubMed Central

    Scheid, Johannes F.; Horwitz, Joshua A.; Bar-On, Yotam; Kreider, Edward F.; Lu, Ching-Lan; Lorenzi, Julio C. C.; Feldmann, Anna; Braunschweig, Malte; Nogueira, Lilian; Oliveira, Thiago; Shimeliovich, Irina; Patel, Roshni; Burke, Leah; Cohen, Yehuda Z.; Hadrigan, Sonya; Settler, Allison; Witmer-Pack, Maggi; West, Anthony P.; Juelg, Boris; Keler, Tibor; Hawthorne, Thomas; Zingman, Barry; Gulick, Roy M.; Pfeifer, Nico; Learn, Gerald H.; Seaman, Michael S.; Bjorkman, Pamela J.; Klein, Florian; Schlesinger, Sarah J.; Walker, Bruce D.; Hahn, Beatrice H.; Nussenzweig, Michel C.; Caskey, Marina

    2016-01-01

    Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env1, in the setting of analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg kg−1 infusions of 3BNC117, separated by 3 or 2 weeks, respectively, are generally well tolerated. Infusions are associated with a delay in viral rebound for 5–9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals, emerging viruses show increased resistance, indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml−1, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9–19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans. PMID:27338952

  2. Treatment of self-injurious behavior using a water mist: initial response suppression and generalization.

    PubMed Central

    Dorsey, M F; Iwata, B A; Ong, P; McSween, T E

    1980-01-01

    This study evaluated the effects of a fine mist of water applied to the face contingent upon self-injurious behavior (SIB) exhibited by profoundly retarded persons. In Experiment 1, results of individual reversal designs showed substantial reductions in a variety of SIB's (mouthing, hand biting, skin tearing, and head banging) for seven participants. In Experiment 2, two participants who frequently bit their hands were each observed in two different settings. Following initial baselines in each setting, a series of manipulations was undertaken to compare the effects of mild verbal punishment ("No") with those of a combined treatment ("No" plus mist procedure). Results in one setting indicated that "No" suppressed SIB only after it was first paired with the water mist. Data also suggested that, once acquired, the punishing properties of "No" could be extended to a second setting in which the mist was never applied, and that these effects could be generalized across therapists. Results of these experiments indicate that the water mist procedure may be an effective alternative to traditional punishment techniques. Although conclusions regarding generalization are limited due to the brevity of the maintenance conditions, the data suggest that treatment gains may be transferred to more acceptable forms of social punishment and reinforcement. PMID:7380756

  3. Caspase-resistant vimentin suppresses apoptosis after photodynamic treatment with a silicon phthalocyanine in Jurkat cells.

    PubMed

    Belichenko, I; Morishima, N; Separovic, D

    2001-06-01

    Oxidative stress, such as photodynamic therapy, is an apoptosis inducer. Apoptosis, as well as photosensitization, have been associated with disruption of the cytoskeletal network. The purpose of the present study was to assess the role of vimentin, a major cytoskeletal protein, in apoptosis after photodynamic treatment (PDT) with the silicon phthalocyanine Pc 4 in human Jurkat T cells. Here we show for the first time that photosensitization with Pc 4 initiates vimentin cleavage and that this event precedes poly(ADP-ribose) polymerase (PARP) degradation. Similar findings were obtained in the presence of C2-ceramide, an inducer of oxidative stress and apoptosis. In the presence of benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoromethylketone, a pan-caspase inhibitor, Pc 4-PDT-induced vimentin and PARP cleavage were abolished. In Jurkat cells transfected with a caspase-resistant vimentin apoptosis was partly suppressed and delayed post-Pc 4-PDT. We suggest that the full-length vimentin confers resistance to nuclear apoptosis after PDT with Pc 4.

  4. Terazosin for the treatment of trauma-related nightmares: a report of 4 cases.

    PubMed

    Nirmalani-Gandhy, Anjali; Sanchez, Deborah; Catalano, Glenn

    2015-01-01

    The selective α1-adrenergic antagonist prazosin has been shown in multiple studies to be effective in targeting trauma-related nightmares in posttraumatic stress disorder. There are limited data regarding the effectiveness of another selective α1-adrenergic antagonist terazosin for the treatment of trauma-related nightmares. We present 4 cases in which terazosin was effectively used to treat nightmares as a second-line agent after prazosin failure. Further studies are needed to validate terazosin as an alternative to prazosin for the treatment of posttraumatic stress disorder-related nightmares.

  5. Paroxetine treatment, following behavioral suppression of PTSD-like symptoms in mice, prevents relapse by activating the infralimbic cortex.

    PubMed

    Bentefour, Yassine; Rakibi, Youness; Bennis, Mohamed; Ba-M'hamed, Saadia; Garcia, René

    2016-02-01

    Clinical studies have shown that post-traumatic stress disorder (PTSD) remission, induced by selective serotonin reuptake inhibitor (SSRI) treatment, is associated with increased prefrontal activation during post-treatment symptom provocation. Other studies have shown that continuation SSRI treatment after remitting from PTSD reduces the rate of relapse. The aim of the present preclinical study was to investigate the relationship between post-treatment prefrontal changes and PTSD relapse prevention. Avoidance conditioning (with a 1.5-mA foot-shock), avoidance extinction and a trauma priming exposure (with a 0.3-mA foot-shock) were used in mice to induce, suppress and reactivate PTSD-like symptoms (including avoidance, fear sensitization, enhanced contextual fear, and anxiety-like behavior), respectively. Paroxetine, injected at 8 mg/kg/day (7 days), was used as SSRI treatment. PTSD-like symptoms were present for at least 30 days and resistant to paroxetine treatment. However, after extinction training (suppressing all PTSD-like symptoms), paroxetine treatment prevented symptom reactivation. Paroxetine treatment also induced infralimbic neuronal activation. However, infralimbic functional tetrodotoxin inactivation abolished the preventive effect of paroxetine treatment on symptom reactivation. The data reveal a potential ability of treatments inducing infralimbic activation to provide prophylactic protection against PTSD relapse.

  6. Bindings of /sup 3/H-prazosin and /sup 3/H-yohimbine to alpha adrenoceptors in the guinea-pig stomach

    SciTech Connect

    Taniguchi, T.; Nishikawa, H.

    1988-01-01

    Alpha adrenoceptor subtypes have been investigated by radioligand binding study in guinea-pig stomach using /sup 3/H-prazosin and /sup 3/H-yohimbine. The specific /sup 3/H-prazosin binding to guinea-pig stomach was saturable and of high affinity with a Bmax of 33 fmol/mg protein. Specific /sup 3/H-yohimbine binding to the tissue was also saturable and of high affinity with a Bmax of 150 fmol/mg protein. Adrenergic drugs competed for /sup 3/H-prazosin binding in order of prazosin > phentolamine > methoxamine > norepinephrine > clonidine > epinephrine > yohimbine. These drugs competed for /sup 3/H-yohimbine binding in order of yohimbine > phentolamine > clonidine > epinephrine > norepinephrine > prazosin > methoxamine. They also examined whether dopamine receptors exist in guinea-pig stomach, using radioligand binding study. Specific binding of /sup 3/H-spiperone, /sup 3/H-apomorphine, /sup 3/H-dopamine and /sup 3/H-domperidone was not detectable in the stomach. Dopaminergic drugs such as dopamine, haloperidol, domperidone and sulpiride competed for /sup 3/H-prazosin binding in order of haloperidol > domperidone > dopamine > sulpiride. Metoclopramide, sulpiride and dopamine competed for /sup 3/H-yohimbine binding in order of metoclopramide > sulpiride > dopamine.

  7. Impairment of contextual conditioned fear extinction after microinjection of alpha-1-adrenergic blocker prazosin into the medial prefrontal cortex.

    PubMed

    Do-Monte, Fabrício H M; Allensworth, Melody; Carobrez, Antônio P

    2010-07-29

    Long-lasting memories of aversive or stressful events have been associated with the noradrenergic system activation. Alpha-1-adrenergic antagonist prazosin has successfully been used in the last years to treat anxiety disorders related to aversive memories recurrence in humans. Contextual conditioned fear extinction paradigm in rats has been used to better understand the mechanisms involved in the attenuation of defensive behaviour after a traumatic situation. Here we investigated the effects of systemic administration of prazosin in the fear extinction processes. Rats were previously paired in a contextual fear conditioning box (1 footshock, 1 mA, 2s duration), further returning to the same box during three consecutive days receiving an intraperitoneal injection of vehicle or prazosin 30 min before (acquisition of extinction; 0.1 or 0.5mg/kg) or immediately after (consolidation of extinction, 0.5 or 1.5mg/kg) each extinction session (10 min). On the last day, all animals were re-exposed undrugged to the apparatus. Since the medial prefrontal cortex (mPFC) has been described as a key structure in the modulation of conditioned fear extinction, the effects of intra-mPFC microinjection (0.2 microl per side) of vehicle (PBS) or prazosin (0.75 or 2.5 nmol) in the acquisition of fear extinction (10 min before extinction session 1) were further evaluated. Subjects were drug-free re-exposed to the same box in the next day (extinction session 2). The percentage of freezing time was used as the memory retention parameter. The results showed that either systemic or intra-mPFC-alpha-1-adrenergic blockade increased the freezing time in the last extinction sessions, suggesting impairment of the extinction of contextual conditioned fear in rats.

  8. Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference.

    PubMed

    Bernardi, Rick E; Lattal, K Matthew

    2012-12-19

    Recent work has shown that α1-adrenergic receptor blockade impairs extinction in fear conditioning paradigms in rodents. However, studies of the role of α1-adrenergic receptors in extinction using other conditioning paradigms, such as those examining the conditioned effects of drug of abuse, have yielded inconsistent results. In this article, we reanalyze and extend previously reported findings of the effect of prazosin, an α1-adrenergic receptor antagonist, on the extinction of a cocaine-induced conditioned place preference in rats, using a median split of performance during the initial test for preference. This new reanalysis, which includes further extinction testing, indicated a paradoxical dose effect. A single post-test administration of a lower dose of prazosin, 0.3 mg/kg intraperitoneally, impaired extinction in rats that showed a below-median preference during initial testing, but had no effect on extinction in rats that showed an above-median preference during initial testing. In contrast, a single post-test administration of a higher dose of prazosin, 1.0 mg/kg intraperitoneally, enhanced extinction in rats that showed an above-median preference during initial testing, but had no effect on extinction in rats that showed a below-median preference during initial testing. Consistent with other studies of fear and drug conditioning, these results suggest the involvement of the α1-adrenergic receptor in the formation of extinction memories, but also indicate a potentially important differential effect on extinction on the basis of the dose of prazosin and the strength of the initial learning.

  9. Using topography to meet wildlife and fuels treatment objectives in fire-suppressed landscapes.

    PubMed

    Underwood, Emma C; Viers, Joshua H; Quinn, James F; North, Malcolm

    2010-11-01

    Past forest management practices, fire suppression, and climate change are increasing the need to actively manage California Sierra Nevada forests for multiple environmental amenities. Here we present a relatively low-cost, repeatable method for spatially parsing the landscape to help the U.S. Forest Service manage for different forest and fuel conditions to meet multiple goals relating to sensitive species, fuels reduction, forest products, water, carbon storage, and ecosystem restoration. Using the Kings River area of the Sierra Nevada as a case study, we create areas of topographically-based units, Landscape Management Units (LMUs) using a three by three matrix (canyon, mid-slope, ridge-top and northerly, southerly, and neutral aspects). We describe their size, elevation, slope, aspect, and their difference in inherent wetness and solar radiation. We assess the predictive value and field applicability of LMUs by using existing data on stand conditions and two sensitive wildlife species. Stand conditions varied significantly between LMUs, with canyons consistently having the greatest stem and snag densities. Pacific fisher (Martes pennanti) activity points (from radio telemetry) and California spotted owl (Strix occidentalis occidentalis) nests, roosts, and sightings were both significantly different from uniform, with a disproportionate number of observations in canyons, and fewer than expected on ridge-tops. Given the distinct characteristics of the LMUs, these units provide a relatively simple but ecologically meaningful template for managers to spatially allocate forest treatments, thereby meeting multiple National Forest objectives. These LMUs provide a framework that can potentially be applied to other fire-dependent western forests with steep topographic relief.

  10. Using Topography to Meet Wildlife and Fuels Treatment Objectives in Fire-Suppressed Landscapes

    PubMed Central

    Viers, Joshua H.; Quinn, James F.; North, Malcolm

    2010-01-01

    Past forest management practices, fire suppression, and climate change are increasing the need to actively manage California Sierra Nevada forests for multiple environmental amenities. Here we present a relatively low-cost, repeatable method for spatially parsing the landscape to help the U.S. Forest Service manage for different forest and fuel conditions to meet multiple goals relating to sensitive species, fuels reduction, forest products, water, carbon storage, and ecosystem restoration. Using the Kings River area of the Sierra Nevada as a case study, we create areas of topographically-based units, Landscape Management Units (LMUs) using a three by three matrix (canyon, mid-slope, ridge-top and northerly, southerly, and neutral aspects). We describe their size, elevation, slope, aspect, and their difference in inherent wetness and solar radiation. We assess the predictive value and field applicability of LMUs by using existing data on stand conditions and two sensitive wildlife species. Stand conditions varied significantly between LMUs, with canyons consistently having the greatest stem and snag densities. Pacific fisher (Martes pennanti) activity points (from radio telemetry) and California spotted owl (Strix occidentalis occidentalis) nests, roosts, and sightings were both significantly different from uniform, with a disproportionate number of observations in canyons, and fewer than expected on ridge-tops. Given the distinct characteristics of the LMUs, these units provide a relatively simple but ecologically meaningful template for managers to spatially allocate forest treatments, thereby meeting multiple National Forest objectives. These LMUs provide a framework that can potentially be applied to other fire-dependent western forests with steep topographic relief. PMID:20872142

  11. Using Topography to Meet Wildlife and Fuels Treatment Objectives in Fire-Suppressed Landscapes

    NASA Astrophysics Data System (ADS)

    Underwood, Emma C.; Viers, Joshua H.; Quinn, James F.; North, Malcolm

    2010-11-01

    Past forest management practices, fire suppression, and climate change are increasing the need to actively manage California Sierra Nevada forests for multiple environmental amenities. Here we present a relatively low-cost, repeatable method for spatially parsing the landscape to help the U.S. Forest Service manage for different forest and fuel conditions to meet multiple goals relating to sensitive species, fuels reduction, forest products, water, carbon storage, and ecosystem restoration. Using the Kings River area of the Sierra Nevada as a case study, we create areas of topographically-based units, Landscape Management Units (LMUs) using a three by three matrix (canyon, mid-slope, ridge-top and northerly, southerly, and neutral aspects). We describe their size, elevation, slope, aspect, and their difference in inherent wetness and solar radiation. We assess the predictive value and field applicability of LMUs by using existing data on stand conditions and two sensitive wildlife species. Stand conditions varied significantly between LMUs, with canyons consistently having the greatest stem and snag densities. Pacific fisher ( Martes pennanti) activity points (from radio telemetry) and California spotted owl ( Strix occidentalis occidentalis) nests, roosts, and sightings were both significantly different from uniform, with a disproportionate number of observations in canyons, and fewer than expected on ridge-tops. Given the distinct characteristics of the LMUs, these units provide a relatively simple but ecologically meaningful template for managers to spatially allocate forest treatments, thereby meeting multiple National Forest objectives. These LMUs provide a framework that can potentially be applied to other fire-dependent western forests with steep topographic relief.

  12. Gain media edge treatment to suppress amplified spontaneous emission in a high power laser

    DOEpatents

    Hackel, Lloyd A.; Soules, Thomas F.; Fochs, Scott N.; Rotter, Mark D.; Letts, Stephan A.

    2008-12-09

    A novel method and apparatus for suppressing ASE and parasitic oscillation modes in a high average power laser is introduced. By roughening one or more peripheral edges of a solid-state crystal or ceramic laser gain media and by bonding such edges using a substantially high index bonding elastomer or epoxy to a predetermined electromagnetic absorbing arranged adjacent to the entire outer surface of the peripheral edges of the roughened laser gain media, ASE and parasitic oscillation modes can be effectively suppressed.

  13. Gain media edge treatment to suppress amplified spontaneous emission in a high power laser

    DOEpatents

    Hackel, Lloyd A [Livermore, CA; Soules, Thomas F [Livermore, CA; Fochs, Scott N [Livermore, CA; Rotter, Mark D [San Ramon, CA; Letts, Stephan A [San Ramon, CA

    2011-02-22

    A novel method and apparatus for suppressing ASE and/or parasitic oscillation modes in a laser is introduced. By roughening one or more peripheral edges of a solid-state crystal or ceramic laser gain media and by bonding such edges to a predetermined electromagnetic absorbing material arranged adjacent to the entire outer surface of the peripheral edges of the roughened laser gain media, ASE, parasitic oscillation modes and/or residual pump energy can be effectively suppressed.

  14. Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence

    DTIC Science & Technology

    2013-07-01

    GA (June, 2011) comparing demographic characteristics of patients with dual diagnosis of AD and PTSD (from this study) and patients with only AD...stimuli. The data showed that those with dual diagnosis had significantly stronger reactions to stress than those with diagnosis of AD alone. A...currently under review in the journal of " Addictive Disorders". The paper explored differences in the pretreatment characteristics of veterans with

  15. The cytotoxicity of the α1-adrenoceptor antagonist prazosin is linked to an endocytotic mechanism equivalent to transport-P.

    PubMed

    Fuchs, Robert; Stracke, Anika; Ebner, Nadine; Zeller, Christian Wolfgang; Raninger, Anna Maria; Schittmayer, Matthias; Kueznik, Tatjana; Absenger-Novak, Markus; Birner-Gruenberger, Ruth

    2015-12-02

    Since the α1-adrenergic antagonist prazosin (PRZ) was introduced into medicine as a treatment for hypertension and benign prostate hyperplasia, several studies have shown that PRZ induces apoptosis in various cell types and interferes with endocytotic trafficking. Because PRZ is also able to induce apoptosis in malignant cells, its cytotoxicity is a focus of interest in cancer research. Besides inducing apoptosis, PRZ was shown to serve as a substrate for an amine uptake mechanism originally discovered in neurones called transport-P. In line with our hypothesis that transport-P is an endocytotic mechanism also present in non-neuronal tissue and linked to the cytotoxicity of PRZ, we tested the uptake of QAPB, a fluorescent derivative of PRZ, in cancer cell lines in the presence of inhibitors of transport-P and endocytosis. Early endosomes and lysosomes were visualised by expression of RAB5-RFP and LAMP1-RFP, respectively; growth and viability of cells in the presence of PRZ and uptake inhibitors were also tested. Cancer cells showed co-localisation of QAPB with RAB5 and LAMP1 positive vesicles as well as tubulation of lysosomes. The uptake of QAPB was sensitive to transport-P inhibitors bafilomycin A1 (inhibits v-ATPase) and the antidepressant desipramine. Endocytosis inhibitors pitstop(®) 2 (general inhibitor of endocytosis), dynasore (dynamin inhibitor) and methyl-β-cyclodextrin (cholesterol chelator) inhibited the uptake of QAPB. Bafilomycin A1 and methyl-β-cyclodextrin but not desipramine were able to preserve growth and viability of cells in the presence of PRZ. In summary, we confirmed the hypothesis that the cellular uptake of QAPB/PRZ represents an endocytotic mechanism equivalent to transport-P. Endocytosis of QAPB/PRZ depends on a proton gradient, dynamin and cholesterol, and results in reorganisation of the LAMP1 positive endolysosomal system. Finally, the link seen between the cellular uptake of PRZ and cell death implies a still unknown pro

  16. Evidence for Using Doxazosin in the Treatment of Posttraumatic Stress Disorder

    PubMed Central

    Smith, Cherish; Koola, Maju Mathew

    2016-01-01

    There is evidence that doxazosin is effective in the treatment of posttraumatic stress disorder (PTSD). Doxazosin is a “me-too” drug of prazosin. Doxazosin has an improved absorption profile and this likely minimizes the risk for unintended adverse hypotensive effects. The availability of doxazosin in the gastrointestinal therapeutic system (GITS) form permits a higher initial daily dose (4 mg/day) while avoiding significant first-dose side effects. The treatment of PTSD with prazosin has several disadvantages due to its short duration of action (6–8 hours), which results in multiple doses being required. Prazosin may wear off and this may lead to nightmares in the latter half of the sleep. Doxazosin has significant advantages over prazosin in clinical practice because it has a long half-life and requires only once-daily dosing. This may lead to better adherence and greater effectiveness in the treatment of PTSD. PMID:27667865

  17. Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids--Synthesis, Characterization, and in Vitro Release Study.

    PubMed

    Oledzka, Ewa; Sawicka, Anna; Sobczak, Marcin; Nalecz-Jawecki, Grzegorz; Skrzypczak, Agata; Kolodziejski, Waclaw

    2015-08-12

    Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance ((1)H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer's rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule.

  18. A Randomized Trial of Comparing the Efficacy of Two Neurofeedback Protocols for Treatment of Clinical and Cognitive Symptoms of ADHD: Theta Suppression/Beta Enhancement and Theta Suppression/Alpha Enhancement

    PubMed Central

    Mohagheghi, Arash; Moghaddasi Bonab, Nafiseh; Chalabianloo, Gholamreza; Noorazar, Seyed Gholamreza; Tabatabaei, Seyed Mahmoud; Farhang, Sara

    2017-01-01

    Introduction. Neurofeedback (NF) is an adjuvant or alternative therapy for children with Attention Deficit Hyperactivity Disorder (ADHD). This study intended to compare the efficacy of two different NF protocols on clinical and cognitive symptoms of ADHD. Materials and Methods. In this clinical trial, sixty children with ADHD aged 7 to 10 years old were randomly grouped to receive two different NF treatments (theta suppression/beta enhancement protocol and theta suppression/alpha enhancement protocol). Clinical and cognitive assessments were conducted prior to and following the treatment and also after an eight-week follow-up. Results. Both protocols alleviated the symptoms of ADHD in general (p < 0.001), hyperactivity (p < 0.001), inattention (p < 0.001), and omission errors (p < 0.001); however, they did not affect the oppositional and impulsive scales nor commission errors. These effects were maintained after an eight-week intervention-free period. The only significant difference between the two NF protocols was that high-frequency alpha enhancement protocol performed better in suppressing omission errors (p < 0.001). Conclusion. The two NF protocols with theta suppression/beta enhancement and theta suppression/alpha enhancement have considerable and comparable effect on clinical symptoms of ADHD. Alpha enhancement protocol was more effective in suppressing omission errors. PMID:28321406

  19. Acid Treatment Enables Suppression of Electron-Hole Recombination in Hematite for Photoelectrochemical Water Splitting.

    PubMed

    Yang, Yi; Forster, Mark; Ling, Yichuan; Wang, Gongming; Zhai, Teng; Tong, Yexiang; Cowan, Alexander J; Li, Yat

    2016-03-01

    We report a strategy for efficient suppression of electron-hole recombination in hematite photoanodes. Acid-treated hematite showed a substantially enhanced photocurrent density compared to untreated samples. Electrochemical impedance spectroscopy studies revealed that the enhanced photocurrent is partly due to improved efficiency of charge separation. Transient absorption spectroscopic studies coupled to electrochemical measurements indicate that, in addition to improved bulk electrochemical properties, acid-treated hematite has significantly decreased surface electron-hole recombination losses owing to a greater yield of the trapped photoelectrons being extracted to the external circuit.

  20. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use Disorders with and without Co-occurring PTSD

    DTIC Science & Technology

    2015-01-01

    AWARD NUMBER: W81XWH-14-1-0025 TITLE: Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use...2015 2. REPORT TYPE Annual 3. DATES COVERED 4 Dec 2013 – 3 Dec 2014 4. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in...Veterans with Alcohol Use Disorders with and without Co-occurring PTSD 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0025 5c. PROGRAM ELEMENT NUMBER

  1. Transplacental pharmacokinetics of glyburide, rhodamine 123, and BODIPY FL prazosin: effect of drug efflux transporters and lipid solubility.

    PubMed

    Cygalova, Lenka Hahnova; Hofman, Jakub; Ceckova, Martina; Staud, Frantisek

    2009-12-01

    Breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are the most abundantly expressed ATP-binding cassette (ABC) drug transporters in the placenta. They recognize a large, partly overlapping spectrum of chemically unrelated compounds and affect their transplacental passage. In this study we investigate the effect of Bcrp and P-gp on the transplacental pharmacokinetics of their specific and common substrates employing the technique of dually perfused rat placenta. We show that the clearance of rhodamine 123 (P-gp substrate), glyburide (BCRP substrate) and BODIPY FL prazosin (P-gp and BCRP substrate) in fetal-to-maternal direction is 11, 11.2 and 4 times higher, respectively, than that in the maternal-to-fetal direction. In addition, all of these substances were found to be transported from the fetal compartment even against concentration gradient. We thus demonstrate the ability of placental ABC transporters to hinder maternal-to-fetal and accelerate fetal-to-maternal transport in a concentration-dependent manner. However, by means of pharmacokinetic modeling we describe the inverse correlation between lipid solubility of a molecule and its active transport by placental ABC efflux transporters. Therefore, in the case of highly lipophilic substrates, such as BODIPY FL prazosin in this study, the efficacy of efflux transporters to pump the molecule back to the maternal circulation is markedly limited.

  2. Highly Sensitive Fluorescence Methods for the Determination of Alfuzosin, Doxazosin, Terazosin and Prazosin in Pharmaceutical Formulations, Plasma and Urine.

    PubMed

    Guo, Xiaozhen; Wu, Hao; Guo, Shiwen; Shi, Yating; DU, Juanli; Zhu, Panpan; DU, Liming

    2016-01-01

    Polymeric ionic liquid-coated magnetic nanoparticles have been successfully prepared as adsorbents for the magnetic solid-phase extraction of four drugs, namely alfuzosin, doxazosin, terazosin and prazosin, from pharmaceutical preparations, urine samples and plasma samples. The four drugs were detected by fluorescence spectrophotometer. Several extraction parameters, including the pH of the solution; the type, ratio and volume of the desorbing reagent; the amount of adsorbent; the time of the extraction and desorption processes; and the addition of NaCl, were investigated and optimized. Linear responses were determined for the four drugs in the concentration range of 0.5 - 45 ng mL(-1). The limit of detection values for alfuzosin, doxazosin, terazosin and prazosin, which were defined as three times the standard deviation of a blank sample, were determined to be 0.035, 0.034, 0.027 and 0.028 ng mL(-1) (n = 11), respectively. Furthermore, this new method gave preconcentration factors of 114.5, 111.3, 111.1 and 108.5 for these four drugs.

  3. The peripubertal gender-dysphoric child: puberty suppression and treatment paradigms.

    PubMed

    Olson, Johanna; Garofalo, Robert

    2014-06-01

    Gender-nonconforming youth are emerging at increasingly younger ages, and those experiencing gender dysphoria are seeking medical care at, or sometimes even before, the onset of puberty. Youth with gender dysphoria are at high risk for depression, anxiety, isolation, self-harm, and suicidality at the onset of a puberty that feels wrong. Medical providers would benefit from understanding interventions that help gender-nonconforming children and youth thrive. The use of gonadotropin-releasing hormone (GnRH) agonists to block the onset of an undesired puberty in youth with gender dysphoria is a relatively new practice, particularly in the United States. These medications shut down the hypothalamic-pituitary-gonadal axis (HPG), and the production of either testosterone or estrogen is temporarily halted. Puberty blocking allows a young person to explore gender and participate more fully in the mental health therapy process without being consumed by the fear of an impending developmental process that will result in the acquisition of undesired secondary sexual characteristics. GnRH agonists have been used safely for decades in children with other medical conditions, including central precocious puberty. Potential side effects of GnRH agonists include diminished bone density, injection site problems, emotional instability, and weight gain. Preliminary data have shown GnRH agonists to be very helpful in improving behavioral and overall functioning outcomes. Puberty suppression should ideally begin in the first stages of pubertal development and can be given via intramuscular or subcutaneous injections, or via an implant that is inserted in the upper arm. Monitoring to assure suppression of the HPG axis should occur regularly. Gender-nonconforming youth who remain gender dysphoric can go on to receive cross-sex hormones for phenotypic gender transition when they are older. GnRH agonists have changed the landscape of medical intervention for youth with gender dysphoria and

  4. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.

    PubMed

    Soraya, Hamid; Clanachan, Alexander S; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Ghazi-Khansari, Mahmoud; Garjani, Alireza

    2014-08-15

    Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP-activated protein kinase (AMPK). In the present study, the effect of chronic pre-treatment with metformin on cardiac dysfunction and toll-like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n=6): normal control and groups were injected isoproterenol after chronic pre-treatment with 0, 25, 50, or 100mg/kg of metformin twice daily for 14 days. Isoproterenol (100mg/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp/dtmax and LVdp/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-α and IL-6. However, the lower doses of 25 and 50mg/kg were more effective than 100mg/kg. Phosphorylated AMPKα (p-AMPK) in the myocardium was significantly elevated by 25mg/kg of metformin, slightly by 50mg/kg, but not by 100mg/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.

  5. Xylanase Treatment Suppresses Light- and Heat-Induced Yellowing of Pulp

    PubMed Central

    Zhang, Daolei; Li, Xuezhi; Wang, Meimei; Ye, Yanxin; Du, Jian; Lu, Xianqin; Zhao, Jian

    2016-01-01

    Xylanase is commonly applied in pulp and paper industries to ease cost-related and environmental pressures. The effect of xylanase treatment on pulp bleaching is well-established, however, few studies were conducted on the effects of xylanase treatment in pulp yellowing, especially the mechanism of pulp yellowing inhibition by xylanase treatment. In this study, pure xylanase (EC 3.2.1.8) was applied to treat wheat straw chemical pulp (CP) and poplar chemi-thermo-mechanical pulp (CTMP) to determine their effects on pulp brightness and on light- and heat-induced yellowing. The xylanase treatment decreased the post-color number of the pulps during light- and heat-induced yellowing. However, differences were observed in the yellowing inhibition between the wheat straw CP and poplar CTMP. The changes in chemical components of pulps after the xylanase treatment, for example, lignin, hemicellulose, and HexA contents, and analysis of UV–vis absorption spectra and Fourier transform infrared-attenuated total reflectance spectrum were used to explore the pulp yellowing inhibition causes by the xylanase treatment. PMID:27917912

  6. Prazosin has low potency at α1A-adrenoceptors and high potency at α1D -adrenoceptors in rat vas deferens.

    PubMed

    Docherty, J R

    2013-10-01

    (1) We have investigated α1 -adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens. (2) Contractions to noradrenaline were investigated in the absence or presence of the noradrenaline transporter blocker cocaine. (3) In the absence of cocaine, contractions to noradrenaline were potently antagonized by RS100329, but not by BMY7378, and so are mediated mainly by α1A -adrenoceptors. (4) In the presence of cocaine, noradrenaline potency was increased, particularly in terms of low concentrations and phasic contractions. Contractions to low concentrations of noradrenaline in the presence of cocaine were resistant to RS100329 but potently antagonized by BMY7378, demonstrating that α1D-adrenoceptors are additionally involved in contractions amplified by cocaine. (5) In the absence of cocaine, prazosin exhibited relatively low potency as an antagonist against the α1A-adrenoceptor-mediated component to the response. In the presence of cocaine, prazosin exhibited higher potency against the α1D-adrenoceptor-mediated component. (6) In conclusion, prazosin has previously unreported selectivity for α1D-over α1A -adrenoceptors in functional studies of rat vas deferens. Contractions of rat vas deferens are mediated by α1A-and α1D -adrenoceptors. The range of prazosin potencies and of receptor subtypes previously reported in rat vas deferens may be explained by the presence of these two subtypes.

  7. Minocycline treatment suppresses juvenile development and growth by attenuating insulin/TOR signaling in Drosophila animal model

    PubMed Central

    Yun, Hyun Myoung; Noh, Sujin; Hyun, Seogang

    2017-01-01

    Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG’s TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling. PMID:28317899

  8. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor.

    PubMed

    Pine, Polly R; Chang, Betty; Schoettler, Nathan; Banquerigo, Mona L; Wang, Su; Lau, Angela; Zhao, Feifei; Grossbard, Elliott B; Payan, Donald G; Brahn, Ernest

    2007-09-01

    Spleen tyrosine kinase (Syk), a key mediator of immunoreceptor signaling in inflammatory cells, is essential for immune complex-mediated signal transduction initiated by activated receptors for immunoglobulin G. In collagen-induced arthritis, R788/R406, a novel and potent small molecule Syk inhibitor suppressed clinical arthritis, bone erosions, pannus formation, and synovitis. Serum anti-collagen type II antibody levels were unaltered, while the half-life of exogenous antibody was extended when co-administered with R406. Expression of the targeted kinase (Syk) in synovial tissue correlated with the joint level of inflammatory cell infiltrates and was virtually undetectable in treated rats. Syk inhibition suppressed synovial cytokines and cartilage oligomeric matrix protein (COMP) in serum, suggesting a sensitive and reliable biomarker for R406 activity. These results highlight the role of activating Fcgamma receptors in inflammatory synovitis and suggest that interruption of the signaling cascade with a novel Syk inhibitor may be a useful addition to immunosuppressive disease-modifying anti-rheumatic drugs currently used in the treatment of human autoimmune diseases such as rheumatoid arthritis.

  9. Effects of single and repeated treatment with antidepressants on apomorphine-induced yawning in the rat: the implication of alpha-1 adrenergic mechanisms in the D-2 receptor function.

    PubMed

    Delini-Stula, A; Hunn, C

    1990-01-01

    Acute (10 or 20 mg/kg IP) and subchronic (2 x 5 or 10 mg/kg IP daily for 7 days) effects of desipramine, imipramine, maprotiline, (+)- and (-)-oxaprotiline enantiomers as well as selective 5-HT-uptake inhibitors citalopram and ifoxetine on yawning, induced by low doses of apomorphine, were investigated in the rat. In addition, the effects of alpha-1 receptor agonist adrafinil and antagonist prazosin were also tested. After acute treatment, desipramine, the stereoselective NA-uptake inhibiting (+)-enantiomer of oxaprotiline, and the alpha-1 agonist adrafinil, markedly and significantly suppressed yawning. Prazosin, in contrast, clearly potentiated it. This potentiating effect was abolished by the pretreatment with (+)-oxaprotiline and adrafinil. Other drugs were inactive. After subchronic administration, yawning was antagonized by NA-uptake-inhibiting antidepressants, including imipramine and maprotiline. By comparison to the acute treatment, the inhibitory effects of desipramine and (+)-oxaprotiline were considerably enhanced. Neither selective 5-HT-uptake inhibitors nor (-)-oxaprotiline (levoprotiline) were active. Antidepressants therefore modulate the functional activity of D-2 receptors, activated by low doses of apomorphine, predominantly by the virtue of their noradrenergic enhancing properties. This modulatory effect appears to be mediated by alpha-1 adrenergic receptors.

  10. Suppressive Effects of Resveratrol Treatment on The Intrinsic Evoked Excitability of CA1 Pyramidal Neurons

    PubMed Central

    Meftahi, Gholamhossein; Ghotbedin, Zohreh; Eslamizade, Mohammad Javad; Hosseinmardi, Narges; Janahmadi, Mahyar

    2015-01-01

    Objective Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neu- ronal function, little effort, if any, has been made to investigate the cellular effect of res- veratrol treatment on intrinsic neuronal properties. Materials and Methods This experimental study was performed to examine the acute effects of resveratrol (100 µM) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp re- cording under current clamp conditions. Results Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity. PMID:26464825

  11. Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation.

    PubMed

    McKallip, Robert J; Hagele, Harriet F; Uchakina, Olga N

    2013-10-17

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  12. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    PubMed Central

    McKallip, Robert J.; Hagele, Harriet F.; Uchakina, Olga N.

    2013-01-01

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB. PMID:24141285

  13. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

    PubMed

    McKallip, Robert J; Ban, Hao; Uchakina, Olga N

    2015-01-01

    Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

  14. Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status

    PubMed Central

    Blum, A; Arnold, R; Stolte, M; Fischer, M; Koelz, H; the, F

    2000-01-01

    BACKGROUND AND AIMS—Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of Helicobacter pylori infection influences the response.
METHODS—After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status.
RESULTS—The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the H pylori positive group and 66%, 73%, 64%, and 71% in the H pylori negative group. In H pylori positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2-31.0; p<0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI −6.7-20.4) or ranitidine 150 mg (8.9%, 95% CI −4.2-21.9). There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups. The six month relapse rate of symptoms requiring treatment was low (<20%) in all groups.
CONCLUSIONS—Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori. The effect of weaker acid inhibition was unsatisfactory.


Keywords: functional dyspepsia; omeprazole; ranitidine

  15. The effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin on the anxiolytic effect of citalopram in conditioned fear stress in the rat.

    PubMed

    Takamura, Naoki; Masuda, Takahiro; Inoue, Takeshi; Nakagawa, Shin; Koyama, Tsukasa

    2012-10-01

    Several studies have shown that the α₁-adrenoreceptor is involved in controlling extracellular serotonin levels. The administration of the α₁-adrenoreceptor antagonist prazosin was shown to decrease extracellular serotonin levels in the hippocampus, the prefrontal cortex and the raphe nucleus, while the administration of the α₁-adrenoreceptor agonist cirazoline was shown to increase serotonin levels. Furthermore, the elevation of serotonin levels induced by the selective serotonin reuptake inhibitor (SSRI) citalopram was attenuated by prazosin. Thus, α₁-adrenoreceptor antagonists may affect SSRI-induced increases in extracellular serotonin levels and their antidepressive and anxiolytic effects. However, little is known about the influence of α₁-adrenoreceptor antagonists on the behavioral pharmacological effects of SSRIs. The conditioned fear stress-induced freezing behavior is an animal model of anxiety and can detect the anxiolytic effect of SSRIs. To clarify whether an α₁-adrenoreceptor antagonist affects the anxiolytic action of SSRIs, we examined the effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin and the SSRI citalopram using the contextual conditioned fear stress model. Low-dose prazosin (0.03 mg/kg) significantly attenuated the citalopram (3 mg/kg)-induced decrease in conditioned freezing. Moreover, high-dose (0.5 mg/kg), but not low-dose (0.03 mg/kg), prazosin significantly attenuated citalopram (10 mg/kg)-induced decreases in conditioned freezing. These drugs did not affect the spontaneous motor activity of the rats. Therefore, these results suggest that blocking the α₁-adrenoreceptor decreases the anxiolytic effect of citalopram.

  16. A personal light-treatment device for improving sleep quality in the elderly: dynamics of nocturnal melatonin suppression at two exposure levels.

    PubMed

    Figueiro, Mariana G; Bierman, Andrew; Bullough, John D; Rea, Mark S

    2009-05-01

    Light treatment has been used as a non-pharmacological tool to help mitigate poor sleep quality frequently found in older people. In order to increase compliance to non-pharmacological light treatments, new, more efficacious light-delivery systems need to be developed. A prototype personal light-treatment device equipped with low brightness blue light-emitting diodes (LEDs) (peak wavelength near 470 nm) was tested for its effectiveness in suppressing nocturnal melatonin, a measure of circadian stimulation. Two levels of corneal irradiance were set to deliver two prescribed doses of circadian light exposure. Eleven older subjects, between 51 and 80 yrs of age who met the selection criteria, were exposed to a high and a low level of light for 90 min on separate nights from the personal light-treatment device. Blood and saliva samples were collected at prescribed times for subsequent melatonin assay. After 1 h of light exposure, the light-induced nocturnal melatonin suppression level was about 35% for the low-light level and about 60% for the high-light level. The higher level of blue light suppressed melatonin more quickly, to a greater extent over the course of the 90 min exposure period, and maintained suppression after 60 min. The constant exposure of the low-light level resulted in a decrease in nocturnal melatonin suppression for the last sampling time, whereas for the high-light level, suppression continued throughout the entire exposure period. The present study performed with healthy adults suggests that the tested personal light-treatment device might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders; however, the acceptance and effectiveness of personal light-treatment devices by older people and by other segments of the population suffering from sleep disorders in a real-life situation need to be directly tested.

  17. Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis.

    PubMed

    Wilk, Christian Matthias; Heinzler, Niklas; Boquoi, Amelie; Cadeddu, Ron-Patrick; Strapatsas, Tobias; Dienst, Ariane; Majidi, Fatemeh; Deenen, René; Bruns, Ingmar; Schroeder, Thomas; Köhrer, Karl; Haas, Rainer; Kobbe, Guido; Fenk, Roland

    2016-11-15

    New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first-line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first-line treatment including induction therapy, cytotoxic stem cell mobilization and high-dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34(+) HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long-term HSPC proliferation in vitro. We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF-β signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long-term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF-β signaling pathway.

  18. 7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

    PubMed Central

    Ma, Rui; Zhang, Jisheng; Liu, Xiaoyu; Yue, Shaoheng; Zhao, Qing

    2016-01-01

    Acute kidney injury (AKI) is a common syndrome which is strongly linked to high morbidity and mortality. Hypoxia is the leading cause of AKI and the proximal renal tubular cells are the most damaged part in the kidney during this period. It has been observed that 7,8-dihydroxyflavone (7,8-DHF) plays a protective role by acting on antiapoptosis and antioxidative stress. In this study we explored functions of 7,8-DHF in protecting human proximal tubular cell line HK-2 from hypoxia insults. We observed that treatment of 7,8-DHF could improve the viability of ischemic cell. Mechanistically, we found that 7,8-DHF could elevate the expression of cysteine-rich protein 61 (Cyr61), a protective immediate early gene in AKI. In addition, treatment of 7,8-DHF decreased CCAAT/enhancer-binding protein homologous protein (CHOP) expression, which is a marker protein during endoplasmic reticulum (ER) stress activation. Intriguingly, overexpression of Cyr61 significantly reduced CHOP expression. Taken together, our results provide novel insights into the possible protective role of 7,8-DHF by activating Cyr61 signaling and suppressing ER stress in hypoxic HK-2 cells which have potential clinical implications for the treatment of AKI. PMID:28116298

  19. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    SciTech Connect

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    2011-11-15

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  20. [Treatment of multiple myeloma with intravenous pamidronate. Pain prevention and suppression of hypercalcemia risk].

    PubMed

    Díaz, Carlos; Soutelo, María J; Quiroga, Luis; Palmer, Luis; Lutfi, Rubén

    2004-01-01

    In a prospective clinical study, with the patient as its own control, we selected patients with stage III multiple myeloma. We treated them monthly with intravenous (i.v.) Disodic Pamidronate: 90 mg in 2 to 21 cycles. Four patients died during the study. The remaining 13 patients presented reduced bone resorption urinary markers (D-Pyr mainly) as well as urinary calcium (bone turnover reduction). Both effects (metabolic interchange reduction and calcium variation) did not show a direct relationship, being the 1st magnitude proportional to the baseline level and the 2nd independent from it. We noted pain reduction (VAS: visual analogs scale), low analgesic consumption, and the absence of future skeletal problems. The treatment tolerance was good. All these factors contribute to justify the welfare of the patient demonstrated by ECOG (Eastern Cooperative Oncology Group), not only improving the average results but also extending this improvement to future results. Our observation suggests that under strict procedures, this treatment could be very adequate in patients with advanced multiple myeloma independent of the state of the disease at the beginning of the study.

  1. Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina.

    PubMed

    Zawilska, Jolanta B; Sadowska, Magdalena

    2002-01-01

    The chick pineal gland and retina synthesize melatonin in a circadian rhythm with high levels during the night. The rhythmic changes in the hormone production result predominantly from the fluctuation in the activity of serotonin N-acetyltransferase (AA-NAT), a penultimate and key regulatory enzyme in melatonin biosynthesis. The aim of this study was to analyze the effects of an acute and prolonged in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, ip) on the nocturnal increase in AA-NAT activity in chick pineal gland and retina. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2 h, while in prolonged experiments the glucocorticoid was given once daily for 7 days and the animals were killed 26-32 h after the last injection. Acute administration of dexamethasone did not affect AA-NAT activity in the chick pineal gland and retina. In the pineal glands and retinas of chicks that were treated with dexamethasone for one week and then killed at the end of the light phase of the 12:12 h light-dark cycle, AA-NAT activity was significantly higher than the enzyme activity found in tissues isolated from the vehicle-treated (control) animals. In addition to that, the nocturnal increase in pineal and, to a lower extent, retinal AA-NAT activity was significantly lower in dexamethasone-treated birds when compared with the respective control groups. It is suggested that prolonged treatment of animals with dexamethasone reduces the amplitude of the rhythmic melatonin production, a phenomenon which may affect chronobiological processes being under control of this hormone.

  2. Disruption of actin filaments and suppression of pancreatic cancer cell viability and migration following treatment with polyisoprenylated cysteinyl amides

    PubMed Central

    Nkembo, Augustine T; Salako, Olufisayo; Poku, Rosemary A; Amissah, Felix; Ntantie, Elizabeth; Flores-Rozas, Hernan; Lamango, Nazarius S

    2016-01-01

    Pancreatic cancer is characterized by K-Ras mutations in over 90% of the cases. The mutations make the tumors aggressive and resistant to current therapies resulting in very poor prognoses. Valiant efforts to drug mutant K-Ras and related proteins for the treatment of cancers with Ras mutations have been elusive. The need thus persists for therapies to target and suppress the hyperactive K-Ras mutant proteins to normal levels of activity. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) of polyisoprenylated methylated protein methyl esterase (PMPMEase) were designed to disrupt polyisoprenylated protein metabolism and/or functions. The potential for PCAIs to serve as targeted anticancer agents for pancreatic cancer was evaluated in pancreatic ductal adenocarcinoma (PDAC) cell lines expressing mutant (MIAPaCa-2 and Panc-1) and wild type (BxPC-3) K-Ras proteins. The PCAIs inhibited MIAPaCa-2 and BxPC-3 cell viability and induced apoptosis with EC50 values as low as 1.9 µM. The PCAIs, at 0.5 µM, inhibited MIAPaCa-2 cell migration by 50%, inhibited colony formation and disrupted F-actin filament organization. The PCAIs blocked MIAPaCa-2 cell progression at the G0/G1 phase. These results reveal that the PCAIs disrupt pertinent biological processes that lead to pancreatic cancer progression and thus have the potential to act as targeted effective treatments for pancreatic cancer. PMID:27904769

  3. Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment.

    PubMed

    Cotella, E M; Mestres Lascano, I; Franchioni, L; Levin, G M; Suárez, M M

    2013-07-01

    Abstract The early-life environment has many long-term effects on mammals. Maternal interaction and early stressful events may affect regulation of the HPA axis during adulthood, leading to differential glucocorticoid secretion in response to stressful situations. These adverse experiences during postnatal development may even sensitize specific neurocircuits to subsequent stressors. Later in life, the overreaction of the HPA axis to stress can constitute a risk factor for metabolic and mental diseases. As tricyclic antidepressants are known to correct glucocorticoid hypersecretion during depression, we treated maternally separated animals with amitriptyline, at a lower dose than habitually used in depression models, to prevent the response to chronic stress during adulthood. Male Wistar rats were separated from the mother for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, animals were subjected to chronic variable stress during 24 d (five types of stressors at different times of day). During the stress, protocol rats were orally administered amitriptyline (5 mg/kg) daily. We observed that maternal separation caused a reduction in plasma ACTH levels (p < 0.05), but evoked hypersecretion of corticosterone (p < 0.05) when it was combined with stress in adulthood. This rise was completely prevented by antidepressant treatment with amitriptyline.

  4. Modulation of the gut microbiota with antibiotic treatment suppresses whole body urea production in neonatal pigs.

    PubMed

    Puiman, Patrycja; Stoll, Barbara; Mølbak, Lars; de Bruijn, Adrianus; Schierbeek, Henk; Boye, Mette; Boehm, Günther; Renes, Ingrid; van Goudoever, Johannes; Burrin, Douglas

    2013-02-01

    We examined whether changes in the gut microbiota induced by clinically relevant interventions would impact the bioavailability of dietary amino acids in neonates. We tested the hypothesis that modulation of the gut microbiota in neonatal pigs receiving no treatment (control), intravenously administered antibiotics, or probiotics affects whole body nitrogen and amino acid turnover. We quantified whole body urea kinetics, threonine fluxes, and threonine disposal into protein, oxidation, and tissue protein synthesis with stable isotope techniques. Compared with controls, antibiotics reduced the number and diversity of bacterial species in the distal small intestine (SI) and colon. Antibiotics decreased plasma urea concentrations via decreased urea synthesis. Antibiotics elevated threonine plasma concentrations and turnover, as well as whole body protein synthesis and proteolysis. Antibiotics decreased protein synthesis rate in the proximal SI and liver but did not affect the distal SI, colon, or muscle. Probiotics induced a bifidogenic microbiota and decreased plasma urea concentrations but did not affect whole body threonine or protein metabolism. Probiotics decreased protein synthesis in the proximal SI but not in other tissues. In conclusion, modulation of the gut microbiota by antibiotics and probiotics reduced hepatic ureagenesis and intestinal protein synthesis, but neither altered whole body net threonine balance. These findings suggest that changes in amino acid and nitrogen metabolism resulting from antibiotic- or probiotic-induced shifts in the microbiota are localized to the gut and liver and have limited impact on whole body growth and anabolism in neonatal piglets.

  5. Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Chiuso-Minicucci, Fernanda; Ishikawa, Larissa Lumi Watanabe; Mimura, Luiza Ayumi Nishiyama; Fraga-Silva, Thais Fernanda de Campos; França, Thais Graziela Donegá; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Marques, Camila; Ikoma, Maura Rosane Valerio; Sartori, Alexandrina

    2015-01-01

    Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund’s Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150μg) was co-administered on days 3 and 11. The administration of 1,25(OH) 2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH) 2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH) 2D3 was able to control EAE development. PMID:25965341

  6. Experimental autoimmune anterior uveitis (EAAU): induction by melanin antigen and suppression by various treatments.

    PubMed

    Broekhuyse, R M; Kuhlmann, E D; Winkens, H J

    1993-02-01

    The uveitogenicity of melanin has been a controversial subject for a long time, presumably as a result of the use of ill-defined preparations in the experiments. We have developed procedures for the preparation of purified uveitogenic melanins from the retinal pigment epithelium and choroid that are free from pathogenic retinal photoreceptor proteins. The active melano-antigen is located at the surface of the melanin granules and is probably identical in both tissues. It retains its pathogenicity in hot polar detergent and during in vitro proteolysis, but it is inactivated by macrophage phagocytosis and hydrolysis in hot hydrochloric acid. Lewis rats immunized with microgram doses of bovine retinal pigment epithelial or choroidal melanin develop severe experimental autoimmune anterior uveitis (EAAU) about 10 days later. Retinitis and pinealitis are not observed. Skin melanin prepared in a similar way evokes EAAU as well, but it is only weakly pathogenic. EAAU cannot be transferred by serum, and its development can effectively be inhibited by antibodies to the inciting antigen and by cyclosporin. Vitamin E treatment of the animals causes a delay in its onset. The results indicate that cell-mediated immunity plays a dominant role in the pathogenesis of EAAU. This is the first time it has been shown that purified ocular and skin melanins are able to induce an autoimmune disease. The relevance of this finding for the study of melanin-related immunopathology in man is discussed.

  7. Surface treatment of zinc anodes to improve discharge capacity and suppress hydrogen gas evolution

    NASA Astrophysics Data System (ADS)

    Cho, Yung-Da; Fey, George Ting-Kuo

    The shape change and redistribution of zinc anode material over the electrode during repeated cycling have been identified as the main factors that can limit the life of alkaline zinc-air batteries. Li 2O-2B 2O 3 (lithium boron oxide, LBO) glass with high Li + conductivity and stability can be coated on the surface of zinc powders. The structures of the surface-treated and pristine zinc powders were characterized by XRD, SEM, TEM, ESCA and BET analyses. XRD patterns of LBO-coated zinc powders revealed that the coating did not affect the crystal structure. TEM images of LBO-coated on the zinc particles were compact with an average passivation layer of about 250 nm. The LBO layer can prevent zinc from coming into direct contact with the KOH electrolyte and minimize the side reactions within the batteries. The 0.1 wt.% LBO-coated zinc anode material provided an initial discharge capacity of 1.70 Ah at 0.5 V, while the pristine zinc electrode delivered only 1.57 Ah. A surface-treated zinc electrode can increase discharge capacity, decrease hydrogen evolution reaction, and reduce self-discharge. The results indicated that surface treatment should be effective for improving the comprehensive properties of anode materials for zinc-air batteries.

  8. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

    PubMed Central

    Qin, Liang; Xu, Tianyuan; Xia, Leilei; Wang, Xianjin; Zhang, Xiang; Zhang, Xiaohua; Zhu, Zhaowei; Zhong, Shan; Wang, Chuandong; Shen, Zhoujun

    2016-01-01

    Background It has been demonstrated that chloroquine (CQ) enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC). In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo. Methods The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy. Results The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05). In vitro concomitant therapy (DDP and CQ) was more effective in restraining SW13 cell proliferation. DDP could promote cell apoptosis and induce autophagy in SW13 cells. Concomitant therapy further promoted cell apoptosis by inhibiting autophagy. In vivo, we found that concomitant therapy was more potent than DDP monotherapy in inhibiting the growth of xenografted tumors and prolonging the survival of tumor-bearing mice. Conclusion The antitumor ability of DDP was related to autophagy activity, and the concomitant therapy (DDP and CQ) could be an

  9. Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium alpha-luminol (Galavit).

    PubMed

    Jiang, Yuhong; Scofield, Virginia L; Yan, Mingshan; Qiang, Wenan; Liu, Na; Reid, Amy J; Lynn, William S; Wong, Paul K Y

    2006-05-01

    Oxidative stress is involved in many human neuroimmunodegenerative diseases, including human immunodeficiency virus disease/AIDS. The retrovirus ts1, a mutant of Moloney murine leukemia virus, causes oxidative stress and progressive neuro- and immunopathology in mice infected soon after birth. These pathological changes include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell depletion. Astrocytes and thymocytes are directly infected and killed by ts1. Neurons are not infected, but they also die, most likely as an indirect result of local glial infection. Cytopathic effects of ts1 infection in cultured astrocytes are associated with accumulation of the viral envelope precursor protein gPr80env in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress. We have reported (i) that activation of the Nrf2 transcription factor and upregulation of antioxidative defenses occurs in astrocytes infected with ts1 in vitro and (ii) that some ts1-infected astrocytes survive infection by mobilization of these pathways. Here, we show that treatment with a refined monosodium alpha-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2 activation in cultured ts1-infected astrocytes. GVT treatment also inhibits the development of spongiform encephalopathy and gliosis in the central nervous system (CNS) in ts1-infected mice, preserves normal cytoarchitecture in the thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment of infected mice reduces ts1-induced oxidative stress, cell death, and pathogenesis in both the CNS and thymus of treated animals. These studies suggest that oxidative stress mediates ts1-induced neurodegeneration and T-cell loss.

  10. Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation

    PubMed Central

    Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A.; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K.

    2015-01-01

    Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy. PMID:26639668

  11. Simulating Patterns of Patient Engagement, Treatment Adherence, and Viral Suppression: A System Dynamics Approach to Evaluating HIV Care Management

    PubMed Central

    Schwartz, Brian; Palma, Anton

    2015-01-01

    Abstract System dynamics (SD) modeling belongs to the rapidly evolving, interdisciplinary field of system science research. This field adds value to more traditional health research by contributing to the design and testing of complex integrated models of change, to examine health system performance and patient outcomes. Using selected milestones in HIV care management to frame our simulation research, we created a SD model to examine three patient subgroups of women of color (WOC) represented in our multi-site cohort, classified by their health care seeking status at baseline. Asked to reflect on their circumstance 6 months prior to enrollment in the MSE cohort, 53% noted they were receiving some care (In Care, n=341), 31% that they had been seeking care (Seeking Care, n=201), and 16% that they were undecided about seeking care (i.e., answered that they may or may not look for care) for treatment of their HIV (May or May Not Seek Care, n=103). Our SD model compared simulated patterns of patient retention over 24 months in relation to: (1) access to antiretroviral therapy (ART), (2) adherence to ART, and (3) viral suppression. Assessed patterns yielded insights about system capacities and constraints in the context of the SPNS initiative under evaluation. PMID:25561309

  12. Combined administration of alpha1-adrenoceptor antagonist prazosin and beta-blocker propranolol impairs spatial avoidance learning on a dry arena.

    PubMed

    Petrasek, Tomas; Doulames, Vanessa; Prokopova, Iva; Vales, Karel; Stuchlik, Ales

    2010-04-02

    Spatial learning is a widely studied type of animal behavior often considered as a model of higher human cognitive functions. Noradrenergic receptors play a modulatory role in many nerve functions, including vigilance, attention, reward, learning and memory. The present study aimed at studying the effects of separate or combined systemic administration of the alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg) and beta-blocker propranolol (5 and 20 mg/kg) on the hippocampus-dependent learning in the active allothetic place avoidance (AAPA) task. Both centrally active drugs impaired spatial learning when administered together, exerting no effect in separate applications. Locomotion was impaired only in a combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg propranolol). These results suggest an in vivo interaction between these two types of receptors in spatial navigation regulation.

  13. Validated specific HPLC methods for determination of prazosin, terazosin and doxazosin in the presence of degradation products formed under ICH-recommended stress conditions.

    PubMed

    Bakshi, Monika; Ojha, Tina; Singh, Saranjit

    2004-01-27

    The present paper describes development of stability-indicating high-performance liquid chromatographic (HPLC) assay methods for three alpha-adrenergic-blocker drug substances, namely, prazosin, terazosin and doxazosin, in the presence of degradation products generated from forced decomposition studies. Resolution of drugs from degradation products was obtained using a reversed-phase C-18 column using water/acetonitrile/methanol/glacial acetic acid/diethylamine (25:35:40:1:0.017) as mobile phase for prazosin and terazosin and acetonitrile/water/glacial acetic acid/diethylamine (65:35:1:0.02) for doxazosin. The detection was done at 254 nm. The methods were validated with respect to linearity, precision, accuracy, specificity and robustness.

  14. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice.

    PubMed

    Sugino, Haruhiko; Futamura, Takashi; Mitsumoto, Yasuhide; Maeda, Kenji; Marunaka, Yoshinori

    2009-03-17

    There is considerable evidence that schizophrenia is associated with immune system dysregulation. For example, blood and cerebrospinal fluid (CSF) levels of proinflammatory cytokines are significantly increased in schizophrenic patients, and their normalization correlates with improvement in psychotic symptoms. In fact, typical and atypical antipsychotics are reported to modulate immune function in in vitro and in vivo studies. In the present study, we examined the anti-inflammatory effect of antipsychotics, clozapine, olanzapine, risperidone and haloperidol, on serum cytokine levels in lipopolysaccharide (LPS)-treated mice. Atypical antipsychotics, such as clozapine, olanzapine and risperidone, but not haloperidol, suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and up-regulated IL-10. Moreover, only clozapine, robustly increased the serum levels of IL-10. Clozapine reproduced its anti-inflammatory feature in polyinsinic-polycytidylic acid sodium salt (Poly[I:C])-induced inflammation. Thus, the anti-inflammatory effect of clozapine would adapt to inflammation induced by some varieties of antigens. Several receptor ligands, such as 8-OH-DPAT, ketanserin, prazosin and scopolamine, were also examined as to their anti-inflammatory effects on serum cytokine levels in LPS-treated mice. Ketanserin and prazosin, but not 8-OH-DPAT nor scopolamine, behaved similarly to atypical antipsychotics. However, the remarkable increase of serum IL-10 level observed in clozapine was not detected in ketanserin and prazosin. These results suggest the unique efficacy of atypical antipsychotics in the suppression of proinflammatory cytokines, and the increase of anti-inflammatory cytokine, IL-10.

  15. Treatment options for parasomnias.

    PubMed

    Attarian, Hrayr

    2010-11-01

    Parasomnias are undesirable physical or experiential events that occur in and around sleep. Treatments include reassurance in some cases, various forms of cognitive-behavioral therapy (CBT), and pharmacologic agents. Cognitive restructuring, imagery rehearsal, relaxation, hypnosis, desensitization, and anticipatory awakenings are some of the common CBT and nonpharmacologic interventions. Medications that are used belong to a wide variety of pharmacologic classes, such as alpha-blockers (prazosin), tricyclic antidepressants (imipramine and clomipramine), selective serotonin reuptake inhibitors, benzodiazepines (diazepam and clonazepam), anticonvulsants (topiramate and gabapentin), desmopressin acetate, and anticholinergic agents (oxybutynin and tolterodine). Data on efficacy are only available from randomized trials on CBT and prazosin for nightmares and on pharmacologic and alarm therapy for enuresis. No large-scale randomized trials are available to assess the efficacy of the other treatments, and most data come from anecdotal case reports, case series, or small open-label trials.

  16. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    PubMed

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Karuppagounder, Vengadeshprabhu; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Miyashita, Shizuka; Nomoto, Mayumi; Harima, Meilei; Suzuki, Hiroshi; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-08-01

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  17. Effect of alpha(1)-adrenergic antagonist prazosin on behavioral alterations induced by MK-801 in a spatial memory task in Long-Evans rats.

    PubMed

    Stuchlík, A; Petrásek, T; Vales, K

    2009-01-01

    Animal models of neuropsychiatric disorders are current topics in behavioral neuroscience. Application of non-competitive antagonists of NMDA receptors (such as MK-801) was proposed as a model of schizophrenia, as it leads to specific behavioral alterations, which are partly analogous to human psychotic symptoms. This study examined an animal model of schizophrenia induced by a systemic application of MK-801 (0.15 and 0.20 mg/kg) into rats tested in the active allothetic place avoidance (AAPA) task. Previous studies suggested that MK-801 may interact in vivo with other neurotransmitter systems, including noradrenergic system. Our experiments therefore evaluated the hypothesis that both locomotor stimulation and deficit in avoidance behavior in AAPA task induced by this drug would be reversible by application of alpha(1)-adrenergic antagonist prazosin (1 and 2 mg/kg). The results showed that both doses of prazosin partially reversed hyperlocomotion induced by higher doses of MK-801 and an avoidance deficit measured as number of entrances into the shock sector. Interestingly, no effect of prazosin on the MK-801-induced decrease of maximum time between two entrances (another measure of cognitive performance) was observed. These results support previous data showing that prazosin can compensate for the hyperlocomotion induced by MK-801 and newly show that this partial reduction sustains even in the forced locomotor conditions, which are involved in the AAPA task. The study also shows that certain parameters of avoidance efficiency may be closely related to locomotor activity, whereas other measures of cognition may more selectively reflect cognitive changes.

  18. [Actuals of the treatment for gender identity disorder at puberty: introducing the suppression of secondary sexual characteristics from psychotherapy].

    PubMed

    Koh, Jun

    2013-01-01

    We have treated young patients who feel gender dysphoria to help them accept their feelings of disconnection. We tell them that such feelings of disconnection are never strange, so they do not have to be suppressed, and can be expressed. To do that, the most important thing is that their parents firmly accept the situation, whereas they are the ones who also feel the most anxious. We need to provide psychological support carefully. The first major hurdle for children who have gender dysphoria is elementary school, even if parents are accepting. In elementary school, even children can distinguish beween male and female, and there are many situations where there is separation by gender in school events, so it is difficult to realize the expression of disconnection without school support. Therefore, understanding by school teachers is needed. When a school shows understanding, parental anxiety is alleviated. When a teacher provides firm support, children around them are more likely to accept the situation. Accordingly, support for children who have gender dysphoria consists of three pillars. The first of these is to help children accept their feelings of gender dysphoria and feel that they can be expressed. The second is to help their parents accept gender dysphoria and create an environment where it can be expressed. The third is to encourage schools to actively create such an environment. To deal with concrete problems which children face by providing these approaches promptly assists in promoting the social growth of children. Even if children feeling gender dysphoria have active school lives with such support, they face the following major hurdle : the secondary sexual characteristics. It has been reported in not only foreign countries but also Japan that there are many children who become mentally unbalanced and enter a maladaptive state, such as truancy and self-injury, on secondary sexual development. In the West, it has been reported that suppressive therapy

  19. Long-term effect of prazosin and losartan administration on blood pressure, heart, carotid artery, and acetylcholine induced dilation of cardiovascular system of young Wistar rats and SHR.

    PubMed

    Kristek, Frantisek; Malekova, Magdalena; Cacanyiova, Sona

    2013-06-01

    The long-term effects of prazosin and losartan administration on blood pressure, trophicity of the heart and carotid arteries, and responses of the cardiovascular system to acetylcholine, were studied in Wistar rats and spontaneously hypertensive rats (SHRs). Four-week-old rats were treated with prazosin (10 mg/kg b.w./day in tap water) or losartan (20 mg/kg b.w./day in tap water) for 5-6 weeks. BP was measured by plethysmographic method. Ten animals of each group were subjected to in vivo studies and subsequent to morphological investigations. The right jugular vein was cannulated for administration of acetylcholine (0.1, 1, and 10 µg). After perfusion with a glutaraldehyde fixative (120 mmHg), the carotid arteries were embedded in Durcupan ACM, and the inner diameter (ID), wall thickness (WT) (tunica intima and media), cross sectional area (CSA) (tunica intima and media), and WT/ID ratio were calculated. In Wistar rats and SHRs, prazosin and losartan administration produced a decrease in the blood pressure and trophicity of the heart. In Wistar rats, both drugs decreased the WT, CSA, and the WT/ID ratio. In addition, these drugs increased the circumferential stress of the artery without affecting the ID. In contrast, in the SHRs, only losartan administration produced these effects. Importantly, both the drugs improved the responses to acetylcholine in SHRs.

  20. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    PubMed Central

    Seo, K. K.; Lee, M. Y.; Lim, S. W.; Kim, S. C.

    1999-01-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  1. Efficacy of alginate-based reflux suppressant and magnesium-aluminium antacid gel for treatment of heartburn in pregnancy: a randomized double-blind controlled trial

    PubMed Central

    Meteerattanapipat, Pontip; Phupong, Vorapong

    2017-01-01

    The aim of this study was to compare the therapeutic efficacy of alginate-based reflux suppressant and magnesium-aluminium antacid gel for treatment of heartburn in pregnancy. A double-blinded, randomized, controlled trial was conducted. One hundred pregnant women at less than 36 weeks gestation with heartburn at least twice per week were randomized to either alginate-based reflux suppressant or to magnesium-aluminium antacid gel. Details of heartburn were recorded before beginning the treatment and the second week of study. Primary outcome measure was the improvement of heartburn frequency after treatment and secondary outcome were the improvement of heartburn intensity, quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. There was no difference between treatment and control groups in improvement of heartburn frequency (80% vs 88%, p = 0.275), 50% reduction of frequency of heartburn (56% vs 52%, p = 0.688), improvement of heartburn intensity (92% vs 92%, p = 1.000) and 50% reduction of heartburn intensity (68% vs 80% cases, p = 0.075). There were also no significant differences in quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. Alginate-based reflux suppressant was not different from magnesium-aluminium antacid gel in the treatment of heartburn in pregnancy. PMID:28317885

  2. Preparation and transdermal diffusion evaluation of the prazosin hydrochloride-loaded electrospun poly(vinyl alcohol) fiber mats.

    PubMed

    Shen, Xiaobing; Xu, Qian; Xu, Shi; Li, Jie; Zhang, Niping; Zhang, Ling

    2014-07-01

    This study reports on the use of electrospun polyvinyl alcohol (PVA) nanofiber mats loaded with prazosin hydrochloride (PRH) as a transdermal drug delivery system, investigating the morphology of electrospun PVA nanofibers, the in vitro release characteristics of the drug from the as-spun fibers, and the influence of permeation enhancer (water-resoluble azone, WSA) on transdermal diffusion of PRH through a rat skin. The same was also conducted on the PRH -loaded as-cast PVA films for comparison. Results indicated that the morphology of PRH-loaded PVA fibers observed by scanning electron microscopy (SEM) relied on the electrospinning processing parameters, and the addition of WSA had obvious effects on the diameter and morphology of electrospun PVA fibers. The PRH-loaded electrospun PVA fiber mats exhibited much higher accumulated release dose and release rate of PRH than as-cast PVA films. And WAS can improve the release amount and rate of PRH from drug-loaded samples. The content of PRH in receiver was more than that in the stratum corneum and in the dermis. It was concluded that the PRH-loaded electropun PVA fiber mats as a transdermal patches can be a promising candidate for the conventional preparation.

  3. Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Prazosin, Terazosin, and Doxazosin in Pharmaceutical Formulations

    PubMed Central

    Shrivastava, Alankar; Gupta, Vipin B.

    2012-01-01

    The current study was carried out with an attempt to separate similarly structured title drugs by liquid chromatography. Spectrophotometric techniques were generally insufficient under these conditions because of the spectral overlapping of drugs with similar functional groups. The pharmaceutical drugs prazosin, terazosin, and doxazosin contain the same parent quinazoline nucleus, thus making it especially difficult to separate the former two drugs because of their very similar structures. A simple and sensitive method for the routine determination of these drugs in pharmaceutical formulations was attempted. We found that the mobile phase consisting of A: ACN–diethylamine (0.05 ml), B: methanol, and C: 10 mM Ammonium acetate separated these drugs effectively. Separations were carried out on a new Kromasil C18 column (250 × 4.6 mm, 5.0 μm) at 254 nm wavelength. The calibration curve was found to be linear in the range of 2–500 μg/ml. The stated method was then validated in terms of specificity, linearity, precision, and accuracy. Additionally, the proposed method reduced the duration of the analysis. PMID:23008810

  4. Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Prazosin, Terazosin, and Doxazosin in Pharmaceutical Formulations.

    PubMed

    Shrivastava, Alankar; Gupta, Vipin B

    2012-01-01

    The current study was carried out with an attempt to separate similarly structured title drugs by liquid chromatography. Spectrophotometric techniques were generally insufficient under these conditions because of the spectral overlapping of drugs with similar functional groups. The pharmaceutical drugs prazosin, terazosin, and doxazosin contain the same parent quinazoline nucleus, thus making it especially difficult to separate the former two drugs because of their very similar structures. A simple and sensitive method for the routine determination of these drugs in pharmaceutical formulations was attempted. We found that the mobile phase consisting of A: ACN-diethylamine (0.05 ml), B: methanol, and C: 10 mM Ammonium acetate separated these drugs effectively. Separations were carried out on a new Kromasil C18 column (250 × 4.6 mm, 5.0 μm) at 254 nm wavelength. The calibration curve was found to be linear in the range of 2-500 μg/ml. The stated method was then validated in terms of specificity, linearity, precision, and accuracy. Additionally, the proposed method reduced the duration of the analysis.

  5. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice

    PubMed Central

    Su, Jin; Sherman, Alexandra; Doerfler, Phillip A.; Byrne, Barry J.; Herzog, Roland W.; Daniell, Henry

    2015-01-01

    Summary Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. PMID:26053072

  6. Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial

    PubMed Central

    Neely, E. Kirk; Kletter, Gad B.; Lewis, Katherine; Chitra, Surya; Terleckyj, Oksana; Eugster, Erica A.

    2015-01-01

    Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP. PMID:25803268

  7. Suppression of pokeweed mitogen-stimulated immunoglobulin production in patients with rheumatoid arthritis after treatment with total lymphoid irradiation

    SciTech Connect

    Kotzin, B.L.; Strober, S.; Kansas, G.S.; Terrell, C.P.; Engleman, E.G.

    1984-02-01

    Patients with intractable rheumatoid arthritis (RA) were treated with total lymphoid irradiation (TLI, 200 rad). The authors previously reported long-lasting clinical improvement in this group associated with a persistent decrease in circulating Leu-3 (helper subset) T cells and marked impairment of in vitro lymphocyte function. In the present experiments, they studied the mechanisms underlying the decrease in pokeweed mitogen stimulated immunoglobulin (Ig) secretion observed after TLI. Peripheral blood mononuclear cells (PBL) from TLI-treated patients produced 10-fold less Ig (both IgM and IgG) in response to pokeweed mitogen than before radiotherapy. This decrease in Ig production was associated with the presence of suppressor cells in co-culture studies. By using responder cells obtained from normal individuals (allogeneic system), PBL from eight of 12 patients after TLI suppressed Ig synthesis by more than 50%. In contrast, PBL from the same patients before TLI failed to suppress Ig synthesis. PBL with suppressive activity contained suppressor T cells, and the latter cells bore the Leu-2 surface antigen. In 50% of the patients studied suppressor cells were also found in the non-T fraction and were adherent to plastic. Interestingly, the Leu-2/sup +/ cells from TLI-treated patients were no more potent on a cell per cell basis than purified Leu-2/sup +/ cells obtained before TLI. Additional experiments suggested that the suppression mediated by T cells after TLI is related to the increased ratio of Leu-2 to Leu-3 cells observed after radiotherapy.

  8. Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat.

    PubMed

    Landa, A I; Cabrera, R J; Gargiulo, P A

    2006-03-01

    We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 microg/6 microL) prior to NMDA administration (1 microg/2 microL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 +/- 3.28, N = 28) when compared to saline controls (6 and 2 microL, 16.59 +/- 3.20, N = 27) was abolished by prazosin administration (17.04 +/- 5.52, N = 17, and 9.33 +/- 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 +/- 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 +/- 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

  9. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

    PubMed Central

    Baroncelli, Silvia; Pirillo, Maria F.; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Antoni, Anna Degli; Galluzzo, Clementina M.; Stentarelli, Chiara; Amici, Roberta

    2015-01-01

    Abstract There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but <37 copies/ml), and quantifiable HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA <37 copies/ml. Most of them (59/90, 65.6%) had full suppression, with the remaining (31/90, 34.4%) showing low-level viremia (median: 11.9 copies/ml; IQR 7.4–16.3). Among the 17 women with quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46–251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and

  10. Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis

    PubMed Central

    Lien, Chia-Ying; Chuang, Tai-Yuan; Hsu, Chih-Hsiang; Lin, Ching-Lung; Wang, Sheue-Er; Sheu, Shuenn-Jyi; Chien, Chiang-Ting; Wu, Chung-Hsin

    2015-01-01

    Objective This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2-associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with

  11. Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283.

    PubMed

    Petersen, William; Liu, Jingbo; Yuan, Liangping; Zhang, Hongying; Schneiderjan, Matthew; Cho, Yoon-Jae; MacDonald, Tobey J

    2014-11-01

    Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.

  12. VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorptiontdg%ang*tok.

    PubMed

    Nakamichi, Yuko; Udagawa, Nobuyuki; Horibe, Kanji; Mizoguchi, Toshihide; Yamamoto, Yoko; Nakamura, Takashi; Hosoya, Akihiro; Kato, Shigeaki; Suda, Tatsuo; Takahashi, Naoyuki

    2017-02-08

    Long-term treatment with active vitamin D [1α,25(OH)2 D3 ] and its derivatives is effective for increasing bone mass in patients with primary and secondary osteoporosis. Derivatives of 1α,25(OH)2 D3 , including eldecalcitol (ELD), exert their actions through the vitamin D receptor (VDR). ELD is more resistant to metabolic degradation than 1α,25(OH)2 D3 . It is reported that ELD treatment causes a net increase in bone mass by suppressing bone resorption rather than by increasing bone formation in animals and humans. VDR in bone and extraskeletal tissues regulates bone mass and secretion of osteotropic hormones. Therefore, it is unclear what types of cells expressing VDR preferentially regulate the vitamin D-induced increase in bone mass. Here, we examined the effects of 4-week treatment with ELD (50 ng/kg/day) on bone using osteoblast lineage-specific VDR conditional knockout (Ob-VDR-cKO) and osteoclast-specific VDR cKO (Ocl-VDR-cKO) male mice aged 10 weeks. Immunohistochemically, VDR in bone was detected preferentially in osteoblasts and osteocytes. Ob-VDR-cKO mice showed normal bone phenotypes, despite no appreciable immunostaining of VDR in bone. Ob-VDR-cKO mice failed to increase bone mass in response to ELD treatment. Ocl-VDR-cKO mice also exhibited normal bone phenotypes, but normally responded to ELD. ELD-induced FGF23 production in bone was regulated by VDR in osteoblast-lineage cells. These findings suggest that the vitamin D treatment-induced increase in bone mass is mediated by suppressing bone resorption through VDR in osteoblast-lineage cells. © 2017 American Society for Bone and Mineral Research.

  13. Fetal pancreas transplantation in miniature swine. IV. Suppression of DTH and MLR responses by treatment with ultraviolet light-irradiated peripheral blood lymphocytes

    SciTech Connect

    Taura, Y.; Stein, E.; Miyazawa, K.; Mullen, Y. )

    1990-07-01

    Irradiation of peripheral blood lymphocytes of miniature swine with ultraviolet light prevented them from initiating proliferative responses in allogeneic mixed lymphocyte reactions and also reduced IL-2 production in these MLRs. When pigs were injected in a series of 4-5 weekly transfusions with UV-irradiated allogeneic PBL differing at the MHC, PBL of recipient pigs progressively responded less strongly to donor PBL in MLRs over the treatment period. These pigs also gave negligible delayed-type hypersensitivity responses to donor PBL at the end of the treatment period. Of the seven UV-irradiated PBL-treated pigs, four produced no antidonor PBL antibody and three produced antibody. Serum from the three antibody-producing pigs also suppressed MLRs of unrelated PBL. By contrast, pigs that received a series of injections of untreated allogeneic PBL gave strong DTH responses to donor PBL and heightened proliferation in MLRs with donor PBL, and all produced antidonor PBL antibody.

  14. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients.

    PubMed

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic.

  15. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  16. Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression

    PubMed Central

    2013-01-01

    Background. To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. Material and methods. Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. Results. The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. Conclusion. Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy. PMID:23477360

  17. Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.

    PubMed

    Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Gazioglu, Isil; Kolak, Ufuk; Ozbal, Seda; Ergur, Bekir U; Arslan, Sevki; Sen, Alaattin; Topcu, Gulacti

    2016-09-15

    Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata's potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6J mice with MOG35-55/CFA. COWE was administered at a daily dose of 500mg/kg by oral gavage either from the day of immunization (T1) or at disease onset (T2) for 21days. Gene expression analysis was performed using a Mouse Multiple Sclerosis RT² Profiler PCR Array, and further determinations and validations of the identified genes were performed using qPCR. Whole-genome transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K microarrays. Immunohistochemical staining was applied to brain sections of the control and treated mice to examine the degree of degeneration. COWE was further fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in T1, and the disease activity was completely inhibited. In the T2 group, the maximal score was significantly reduced compared with that of the parallel EAE group. The COWE suppression of EAE was associated with a significantly decreased expression of genes that are important in inflammatory signaling, such as TNFα, IL6, NF-κB, CCL5, CXCL9, and CXCK10. On the other hand, the expression of genes involved in myelination/remyelination was significantly increased. Immunohistochemical analysis further supported these effects, showing that the number of infiltrating immune cells was decreased in the brains of COWE-treated animals. In addition, differential

  18. Adrenergic receptor and catecholamine distribution in rat cerebral cortex: binding studies with [3H]prazosin, [3H]idazoxan and [3H]dihydroalprenolol.

    PubMed

    Diop, L; Brière, R; Grondin, L; Reader, T A

    1987-02-03

    The tritiated adrenergic antagonists [3H]dihydroalprenolol ([3H]DHA; beta-receptors), [3H]prazosin ([3H]PRZ; alpha 1-receptors), and [3H]idazoxan ([3H]IDA; alpha 2-receptors) were used to determine the distribution of these sites in 5 defined areas of the adult rat cerebral cortex. The highest density of [3H]PRZ binding was found in the prefrontal cortex, with a lower and homogeneous distribution for the frontal, parietal, occipital and temporal areas. The [3H]IDA binding sites were fairly uniform for all areas, except for the temporal cortex where it was very dense. In contrast, beta-adrenoceptors labelled by [3H]DHA were very homogeneous for all the regions examined. The functional significance of the distribution of alpha 1, alpha 2 and beta-adrenoceptors is discussed in relation to the catecholamine innervation and monoamine contents measured by high performance liquid chromatography.

  19. Pharmacological and non-pharmacological treatments for nightmare disorder.

    PubMed

    Nadorff, Michael R; Lambdin, Karen K; Germain, Anne

    2014-04-01

    Interest in the treatment of nightmares has greatly increased over the last several years as research has demonstrated the clinical significance of nightmare disorder. This paper provides an overview of nightmare disorder, its clinical relevance, and the leading treatments that are available. In particular, the paper defines nightmare disorder and then summarize the recent literature examining the clinical relevance of nightmare disorder, including its relation to post-traumatic stress disorder and other psychiatric conditions. The relation between nightmares and suicidality is also discussed. Recent findings on the treatment of nightmare with imagery rehearsal therapy and prazosin are then summarized. Lastly, the paper comments on potential future uses of nightmare treatment including using imagery rehearsal therapy or prazosin as a first-line intervention for post-traumatic stress disorder and using these treatments as an adjunctive therapy to reduce suicide risk in those at risk of suicide with nightmares.

  20. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    PubMed

    Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson; Costa, Fábio Trindade Maranhão; Oliveira, Alexandre Leite Rodrigues; Höfling, Maria Alice da Cruz; Machado, Dagmar Ruth Stach; Thomé, Rodolfo

    2015-01-01

    Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to

  1. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells

    PubMed Central

    Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson; Costa, Fábio Trindade Maranhão; Oliveira, Alexandre Leite Rodrigues; Höfling, Maria Alice da Cruz; Machado, Dagmar Ruth Stach; Thomé, Rodolfo

    2015-01-01

    Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to

  2. Differential suppression of ethylene biosynthesis and receptor genes in 'Golden Delicious' apple by preharvest and postharvest 1-MCP treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Harvista™, a spraying formulation of 1-MCP, is a recently available tool for managing preharvest on-tree fruit maturation whereas SmartFresh™ is the widely-used treatment for postharvest handling and storage. In the current study, the timing of pre-harvest application and its effects on fruit ripeni...

  3. Chronic fluoxetine treatment suppresses plasticity (long-term potentiation) in the mature rodent primary auditory cortex in vivo.

    PubMed

    Dringenberg, Hans C; Branfield Day, Leora R; Choi, Deanna H

    2014-01-01

    Several recent studies have provided evidence that chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine can facilitate synaptic plasticity (e.g., ocular dominance shifts) in the adult central nervous system. Here, we assessed whether fluoxetine enhances long-term potentiation (LTP) in the thalamocortical auditory system of mature rats, a developmentally regulated form of plasticity that shows a characteristic decline during postnatal life. Adult rats were chronically treated with fluoxetine (administered in the drinking water, 0.2 mg/mL, four weeks of treatment). Electrophysiological assessments were conducted using an anesthetized (urethane) in vivo preparation, with LTP of field potentials in the primary auditory cortex (A1) induced by theta-burst stimulation of the medial geniculate nucleus. We find that, compared to water-treated control animals, fluoxetine-treated rats did not express higher levels of LTP and, in fact, exhibited reduced levels of potentiation at presumed intracortical A1 synapses. Bioactivity of fluoxetine was confirmed by a reduction of weight gain and fluid intake during the four-week treatment period. We conclude that chronic fluoxetine treatment fails to enhance LTP in the mature rodent thalamocortical auditory system, results that bring into question the notion that SSRIs act as general facilitators of synaptic plasticity in the mammalian forebrain.

  4. Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

    PubMed

    Poole, Ashleigh; Knowland, Nicholas; Cooper, Emily; Cole, Rebecca; Wang, Hongchuan; Booth, Lucas; Kacer, Doreen; Tarantini, Francesca; Friesel, Robert; Prudovsky, Igor

    2014-05-01

    FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

  5. Energy controllable steep pulse (ECSP) treatment suppresses tumor growth in rats implanted with Walker 256 carcinosarcoma cells through apoptosis and an antitumor immune response.

    PubMed

    Luo, Xiao-Dong; Sun, Jiang-chuan; Liu, Feng; Hu, Li-Na; Dong, Xiao-Jing; Sun, Di-Na; Xiao, Jin

    2012-01-01

    Electrochemotherapy has been widely used for the treatment of solid tumors, although the underlying mechanism remains unclear. We aimed to investigate the effects of energy controllable steep pulse (ECSP) on the regulation of tumor growth and apoptosis in rats implanted with Walker 256 carcinosarcoma cells. A rat tumor model was established by injection of Walker 256 carcinosarcoma cells into the inguinal area. H&E staining, transmission electron microscopy, and the TUNEL assay were used to detect apoptosis. Concanavalin A-induced lymphocyte transformation and MTT assays were used to assess lymphocyte proliferation. ELISA was used to determine serum cytokine levels. After 2 weeks of ECSP treatment, tumor growth in rats was effectively suppressed, while tumor cell apoptosis was significantly induced compared to the control tumor group. Moreover, ECSP treatment enhanced proliferation and activation of lymphocytes and natural killer (NK) cells. Serum IL-2 and IFN-gamma levels were significantly decreased, and IL-4 and 1-10 levels dramatically increased in rats with control tumors compared to rats without tumors and lacking treatment (p < 0.05). In contrast, ECSP treatment increased IL-2 and IFN-gamma levels, but reduced IL-4 and IL-10 levels to normal values. Moreover, ECSP also increased TNF-alpha production, possibly from peritoneal microphages. Our current study demonstrates that ECSP treatment is able to effectively reduce tumors in rats via induction of apoptosis and activation of the rat antitumor immune response. These data provide insightful information for the future application of ECSP-based electrochemotherapy in clinical trials against solid tumors.

  6. The role of an acute pasireotide suppression test in predicting response to treatment in patients with Cushing's disease: findings from a pilot study.

    PubMed

    Trementino, L; Zilio, M; Marcelli, G; Michetti, G; Barbot, M; Ceccato, F; Boscaro, M; Scaroni, C; Arnaldi, G

    2015-09-01

    Pasireotide is a multireceptor-targeted somatostatin analog effective in the treatment of Cushing's disease (CD). We evaluate the value of an acute pasireotide suppression test (PST) in predicting response to medium/long-term treatment in CD. Nineteen patients with active CD were prospectively investigated at two referral centers from May 2013 to August 2014. Follow-up data (median 6 months; range 1-9 months) were available for sixteen patients. All patients received at 09:00 h a single subcutaneous (sc) injection of 600 μg pasireotide. Serum cortisol and plasma ACTH were assessed before, and every 2 h for 8 h after, drug administration. Late-night salivary cortisol (LNSC) was assessed before and after pasireotide administration. After acute PST, all patients were continued on pasireotide 600 μg sc twice a day. During PST, cortisol and ACTH levels quickly decreased in all patients except one with a mean percentage fall, respectively, of 48.9 ± 24.3 and 48.1 ± 25.4 % compared to baseline. LNSC decreased in about 82 % of patients (14/17) achieving a normalization in five of them. Pasireotide treatment was associated with a normalization of 24-h urinary-free cortisol at last follow-up in about 68 % of patients. A fall >27 % of LNSC during PST calculated by ROC curve was the best parameter in predicting a positive response to treatment with pasireotide (sensitivity 91 %; specificity 100 %; positive predictive value 100 %; negative predictive value 75 %). Acute PST may be useful to identify CD patients who will benefit from pasireotide treatment. A LNSC fall >27 % as well as a LNSC normalization during PST is associated with a probability of 100 % of achieving a favorable response to pasireotide treatment in the medium/long term.

  7. Cellular induction of chronic allotype suppression of IgG2a in Ighb/b homozygous mice and its abrogation by in vivo treatment with anti-CD8 monoclonal antibody

    PubMed Central

    1988-01-01

    We report here the successful induction of allotype suppression in homozygous Ighb/b mice (CB20 or C57BL/6) by neonatal injection of T splenocytes from Igha congenic sensitized mice (BALB/c or BC8, respectively). The sensitization of the T cell donors was achieved by two intravenous injections of B splenocytes from Ighb congenic mice. Treated homozygous Ighb/b mice developed, as of 16-24 wk of age, a chronic suppression of Igh-1b expression (IgG2a of Ighb haplotype). The other productions tested (IgM, IgD, and IgA) of Ighb haplotype were unaffected. In vivo treatment with cytotoxic anti-CD4 or anti-CD8 mAb of mice subjected to chronic Igh-1b suppression clearly showed that CD8+ lymphocytes (suppressor or cytotoxic cell) were essential for the maintenance of the suppression. The suppression was indeed abrogated after a 1-wk treatment with anti-CD8 mAb containing culture supernatant, whereas, the anti-CD4-treated mice continued to be subjected to suppression. This anti-CD8 in vivo treatment was shown to have no effect on thymus but to severely reduce the percentages of CD8+ cells in spleen and in peripheral blood without affecting the percentages of CD4+ cells, leading to a large and rapid Igh-1b expression (up to 0.5 mg per ml of serum, the day after the end of the treatment). This suppression abrogation, and thus the Igh-1b expression, was either transient or permanent. When it was transient, a second 1-wk treatment with anti-CD8 mAb containing culture supernatant induced once again a rapid and significant production of Igh-1b (up to 0.3 mg of Igh-1b per ml of serum). PMID:2902183

  8. [Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia].

    PubMed

    Gotoh, M; Yoshikawa, Y; Otani, T; Kato, T; Kobayashi, M; Kato, K; Saito, M; Kondo, A; Miyake, K

    1990-12-01

    Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction

    PubMed Central

    Ait‐Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

    2006-01-01

    Background Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti‐inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p‐MLC). Methods Female Wistar rats received either 1011 CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham‐PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham‐PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p‐MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham‐PRS. Results PRS significantly increased the number of spike bursts for CRD pressures of 30–60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p‐MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. Conclusion L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic. PMID:16507583

  10. Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines

    PubMed Central

    Simova, Jana; Sapega, Olena; Imrichova, Terezie; Stepanek, Ivan; Kyjacova, Lenka; Mikyskova, Romana; Indrova, Marie; Bieblova, Jana; Bubenik, Jan; Bartek, Jiri; Hodny, Zdenek; Reinis, Milan

    2016-01-01

    Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit. To assess this possibility, here we first show that tumor growth of proliferating mouse TC-1 HPV-16-associated cancer cells in syngeneic mice becomes accelerated by co-administration of TC-1 or TRAMP-C2 prostate cancer cells made senescent by pre-treatment with the anti-cancer drug docetaxel, or lethally irradiated. Phenotypic analyses of tumor-explanted cells indicated that the observed acceleration of tumor growth was attributable to a protumorigenic environment created by the co-injected senescent and proliferating cancer cells rather than to escape of the docetaxel-treated cells from senescence. Notably, accelerated tumor growth was effectively inhibited by cell immunotherapy using irradiated TC-1 cells engineered to produce interleukin IL-12. Collectively, our data document that immunotherapy, such as the IL-12 treatment, can provide an effective strategy for elimination of the detrimental effects caused by bystander senescent tumor cells in vivo. PMID:27448982

  11. Effects of desipramine on prazosin potency at α1A- and α1D-adrenoceptors in rat vas deferens: implications for the α1L-adrenoceptor subclassification.

    PubMed

    Docherty, J R

    2014-12-05

    This study investigates the interaction between cocaine, desipramine and prazosin at α1-adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens. Noradrenaline potency was not significantly affected by desipramine (0.1-1.0 μM) and reduced by desipramine (10 μM), but was increased by the presence of cocaine (3.0-30 μM), particularly in terms of phasic contractions to low concentrations of noradrenaline. In vehicle experiments, prazosin exhibited relatively low potency as an antagonist against the predominantly α1A-adrenoceptor mediated response (pKB 8.50). In the presence of cocaine, prazosin exhibited higher potency against the revealed α1D-adrenoceptor mediated component (e.g. pKB 9.12). In the presence of desipramine, the potency of prazosin was either unchanged or indeed decreased. Cocaine (0.3-30 μM) significantly increased the single pulse nerve-stimulation-evoked contraction, with a maximum increase to 156±12% of control (n=9). In contrast, desipramine in low concentrations (0.1-0.3 μM) produced a small but significant increase to 126.6±5.5% (n=11), but higher concentrations failed to increase the response. In conclusion, desipramine fails to produce sufficient noradrenaline transporter block in low concentrations (0.1 μM) and produces α1-adrenoceptor antagonism in slightly higher concentrations (0.3-1 μM), and so is unsuitable for use in α1-adrenoceptor subclassification studies. Contractions of rat vas deferens are mediated by α1A- and α1D-adrenoceptors, and prazosin has selectivity for α1D- over α1A-adrenoceptors. The α1L-adrenoceptor previously identified in rat vas deferens is the native α1A-adrenoceptor. The range of prazosin potencies and receptor subtypes previously reported in rat vas deferens may be explained by the choice of cocaine or desipramine as noradrenaline transporter blocker.

  12. Repeated landscape-scale treatments following fire suppress a non-native annual grass and promote recovery of native perennial vegetation

    USGS Publications Warehouse

    Munson, Seth M.; Long, A. Lexine; Decker, Cheryl E.; Johnson, Katie A.; Walsh, Kathleen; Miller, Mark E.

    2015-01-01

    Invasive non-native species pose a large threat to restoration efforts following large-scale disturbances. Bromus tectorum (cheatgrass) is a non-native annual grass in the western U.S. that both spreads quickly following fire and accelerates the fire cycle. Herbicide and seeding applications are common restoration practices to break the positive fire-invasion feedback loop and recover native perennial species, but their interactive effects have infrequently been tested at the landscape-scale and repeated in time to encourage long-lasting effects. We determined the efficacy of repeated post-fire application of the herbicide imazapic and seeding treatments to suppressBromus abundance and promote perennial vegetation recovery. We found that the selective herbicide reduced Bromus cover by ~30 % and density by >50 % across our study sites, but had a strong initial negative effect on seeded species. The most effective treatment to promote perennial seeded species cover was seeding them alone followed by herbicide application 3 years later when the seeded species had established. The efficacy of the treatments was strongly influenced by water availability, as precipitation positively affected the density and cover of Bromus; soil texture and aspect secondarily influenced Bromus abundance and seeded species cover by modifying water retention in this semi-arid region. Warmer temperatures positively affected the non-native annual grass in the cool-season, but negatively affected seeded perennial species in the warm-season, suggesting an important role of seasonality in a region projected to experience large increases in warming in the future. Our results highlight the importance of environmental interactions and repeated treatments in influencing restoration outcomes at the landscape-scale.

  13. Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs connected?

    PubMed

    Soraya, Hamid; Farajnia, Safar; Khani, Sajjad; Rameshrad, Maryam; Khorrami, Arash; Banani, Armita; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2012-12-01

    AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI). Besides, the innate immune response through TLRs is activated during MI. In the present study, the effects of short-term treatment with metformin on TLRs activity and its relation with AMPK in isoproterenol-induced MI were assessed in rats. To induce MI, a subcutaneous injection of isoproterenol was given to Wistar rats for two consecutive days. Metformin (25, 50, and 100mg/kg) was orally administered to rats twice daily for two days. Interstitial fibrosis was dose-dependently attenuated in the treated groups in comparison to the MI group (score: 1.25 ± 0.28 with 100 mg/kg metformin versus 3.5 ± 0.28; P<0.001). Further, metformin reduced TLR-dependent inflammatory cytokines as indexed by reduced myocardial levels of TNFα (maximum 68%; P<0.001) and IL6 (maximum 84%; P<0.001) as well as by reduced myocardial MPO activity (25%; P<0.01). It was found that the level of phosphorylated AMPK was significantly upregulated by 165% (P<0.001) when treated with 100 mg/kg of metformin, but not with 25 and 50mg/kg. This was associated with a remarkable suppression of TLR4 expression and reduction of protein level of TLRs adapter protein, MyD88 (P<0.01) in the infarcted myocardium. These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs.

  14. Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

    PubMed Central

    Lider, O; Baharav, E; Mekori, Y A; Miller, T; Naparstek, Y; Vlodavsky, I; Cohen, I R

    1989-01-01

    The ability of activated T lymphocytes to penetrate the extracellular matrix and migrate to target tissues was found to be related to expression of a heparanase enzyme (Naparstek, Y., I. R. Cohen, Z. Fuks, and I. Vlodavsky. 1984. Nature (Lond.). 310:241-243; Savion, N., Z. Fuks, and I. Vlodavsky. 1984. J. Cell. Physiol. 118:169-176; Fridman, R., O. Lider, Y. Naparstek, Z. Fuks, I. Vlodavsky, and I. R. Cohen. 1987. J. Cell. Physiol. 130:85-92; Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We found previously that heparin molecules inhibited expression of T lymphocyte heparanase activity in vitro and in vivo, and administration of a low dose of heparin in mice inhibited lymphocyte traffic and delayed-type hypersensitivity reactions (Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We now report that treatment with commercial or chemically modified heparins at relatively low doses once daily (5 micrograms for mice and 20 micrograms for rats) led to inhibition of allograft rejection and the experimental autoimmune diseases adjuvant arthritis and experimental autoimmune encephalomyelitis. Higher doses of the heparins were less effective. The ability of chemically modified heparins to inhibit these immune reactions was associated with their ability to inhibit expression of T lymphocyte heparanase. There was no relationship to anticoagulant activity. Thus heparins devoid of anticoagulant activity can be effective in regulating immune reactions when used at appropriate doses. PMID:2493485

  15. Suppression of rat and human androgen biosynthetic enzymes by apigenin: Possible use for the treatment of prostate cancer.

    PubMed

    Wang, Xiudi; Wang, Guimin; Li, Xiaoheng; Liu, Jianpeng; Hong, Tingting; Zhu, Qiqi; Huang, Ping; Ge, Ren-Shan

    2016-06-01

    Apigenin is a natural flavone. It has recently been used as a chemopreventive agent. It may also have some beneficial effects to treat prostate cancer by inhibiting androgen production. The objective of the present study was to investigate the effects of apigenin on the steroidogenesis of rat immature Leydig cells and some human testosterone biosynthetic enzyme activities. Rat immature Leydig cells were incubated for 3h with 100μM apigenin without (basal) or with 1ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and 20μM of the following steroid substrates: 22R-hydroxychloesterol (22R), pregnenolone (P5), progesterone (P4), and androstenedione (D4). The medium levels of 5α-androstane-3α, 17β-diol (DIOL), the primary androgen produced by rat immature Leydig cells, were measured. Apigenin significantly inhibited basal, 8BR, 22R, PREG, P4, and D4 stimulated DIOL production in rat immature Leydig cells. Further study showed that apigenin inhibited rat 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17, 20-lyase, and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 11.41±0.7, 8.98±0.10, and 9.37±0.07μM, respectively. Apigenin inhibited human 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 2.17±0.04 and 1.31±0.09μM, respectively. Apigenin is a potent inhibitor of rat and human steroidogenic enzymes, being possible use for the treatment of prostate cancer.

  16. PEDF expression is inhibited by insulin treatment in adipose tissue via suppressing 11β-HSD1.

    PubMed

    Zhou, Yinli; Xu, Fen; Deng, Hongrong; Bi, Yan; Sun, Weiping; Zhao, Yi; Chen, Zonglan; Weng, Jianping

    2013-01-01

    Early intensive insulin therapy improves insulin sensitivity in type 2 diabetic patients; while the underlying mechanism remains largely unknown. Pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, is believed to be involved in the pathogenesis of insulin resistance. Here, we hypothesize that PEDF might be down regulated by insulin and then lead to the improved insulin resistance in type 2 diabetic patients during insulin therapy. We addressed this issue by investigating insulin regulation of PEDF expression in diabetic conditions. The results showed that serum PEDF was reduced by 15% in newly diagnosed type 2 diabetic patients after insulin therapy. In adipose tissue of diabetic Sprague-Dawley rats, PEDF expression was associated with TNF-α elevation and it could be decreased both in serum and in adipose tissue by insulin treatment. In adipocytes, PEDF was induced by TNF-α through activation of NF-κB. The response was inhibited by knockdown and enhanced by over expression of NF-κB p65. However, PEDF expression was indirectly, not directly, induced by NF-κB which promoted 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression in adipocytes. 11β-HSD1 is likely to stimulate PEDF expression through production of active form of glucocorticoids as dexamethasone induced PEDF expression in adipose tissue. Insulin inhibited PEDF by down-regulating 11β-HSD1 expression. The results suggest that PEDF activity is induced by inflammation and decreased by insulin through targeting 11β-HSD1/glucocorticoid pathway in adipose tissue of diabetic patients.

  17. Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species.

    PubMed

    Deng, Guoying; Niu, Kerun; Zhou, Feng; Li, Buxiao; Kang, Yingjie; Liu, Xijian; Hu, Junqing; Li, Bo; Wang, Qiugen; Yi, Chengqing; Wang, Qian

    2017-03-03

    Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress.

  18. Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Deng, Guoying; Niu, Kerun; Zhou, Feng; Li, Buxiao; Kang, Yingjie; Liu, Xijian; Hu, Junqing; Li, Bo; Wang, Qiugen; Yi, Chengqing; Wang, Qian

    2017-03-01

    Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress.

  19. Bcl-2 anti-apoptotic oncoprotein suppresses angiogenesis in non-small cell lung cancer: implications in resistance to photodynamic treatment?

    NASA Astrophysics Data System (ADS)

    Koukourakis, M. I.; Giatromanolaki, A.; Skarlatos, J.; Kosma, L.; Apostolikas, N.; Beroukas, K.

    1998-07-01

    PDT cytotoxicity is likely to occur through photooxidative reactions. In that way mechanisms that define poor oxygenation should be involved in defining resistance to photo-dynamic treatment (PDT). On the other hand bcl-2 anti- apoptotic protein has been shown to delay cell death and protect cells from toxic oxidative products. We examined 134 specimens from T1,2-NO,1 staged patients treated with surgery alone. Specimens were immunohistochemically examined for vascular grade using the JC70 MoAb, and bcl-2 oncoprotein expression. Bcl-2 expression correlated with low vascular grade. Only 3/27 of bcl2+ case had high angiogenesis vs. 34/107 of cases without bcl-2 expression. In the present study we provide evidence that bcl-2 overexpression directly suppresses angiogenesis in non-small cell lung cancer, which obviously results in decreased blood supply and oxygenation. This finding implies that reduced intratumoral angiogenesis and immortalizing oncoprotein overexpression are linked to each other and may have a role in defining tumors resistant to PDT.

  20. Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species

    PubMed Central

    Deng, Guoying; Niu, Kerun; Zhou, Feng; Li, Buxiao; Kang, Yingjie; Liu, Xijian; Hu, Junqing; Li, Bo; Wang, Qiugen; Yi, Chengqing; Wang, Qian

    2017-01-01

    Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress. PMID:28256626

  1. Evaluation of the clinical efficacy of Gonazon implants in the treatment of reproductive pathologies, behavioral problems, and suppression of reproductive function in the male dog.

    PubMed

    Goericke-Pesch, S; Wilhelm, E; Ludwig, C; Desmoulins, P O; Driancourt, M A; Hoffmann, B

    2010-04-15

    Efficacy of a slow-release gonadotropin-releasing hormone (GnRH)-agonist implant (Gonazon) was assessed in 53 male dogs presented with benign prostatic hyperplasia (BPH), hypersexuality, aggressive behavior (either alone or in combination), excessive micturition, or to suppress fertility. Changes in testosterone (T) and estradiol (E2) concentrations and size of testes and prostate were monitored on Weeks 0, +8, and +26 after implantation. Additional measurements during and after this period were performed in 35 dogs. Clinical signs were assessed by the owners. All implants except one were retained throughout the study. Full downregulation of testicular function (T<0.35 nmol/L) was achieved in 46 dogs, five dogs showed partial downregulation (T = 0.36 to 0.47 nmol/L), one dog did not respond, and another one displayed a transient downregulation on Week +18. On Week +8, mean T and E2 levels were reduced by 96% and 62%, respectively, and did not further decrease. Full downregulation (T<0.35 nmol/L) lasted between 6 to >22 mo in most dogs except two. Compared with pretreatment values, mean testicular and prostatic size was reduced (P<0.00001) by 54% and 52%, respectively, on Week +8 and by 68% and 64%, respectively, on Week +26. Relative reduction of prostatic size was more marked in dogs with BPH than in healthy ones on Week +8 (P<0.05) and Week +26 (P<0.02), and clinical signs of BPH disappeared rapidly after implantation. Dogs affected with BPH were significantly older (P<0.001) than nonaffected ones (9.7 vs. 2.5 yr). Hypersexuality was more common in dogs<3 yr of age, and treatment clearly improved clinical signs. Age significantly affected the response to treatment in aggressive dogs; 75% of the cases responded with an improvement. The only minor and possibly treatment-related events observed were a short-lasting exacerbation of clinical signs of BPH (two dogs), increased weight gain (three dogs), and anxiety (three dogs) with one of these dogs developing a blunt

  2. Lifestyle/dietary supplement partial androgen suppression and/or estrogen manipulation. A novel PSA reducer and preventive/treatment option for prostate cancer?

    PubMed

    Moyad, Mark A

    2002-02-01

    There is a large interest in prostate cancer prevention and/or slowing the progression of this disease via dietary/lifestyle/supplement interventions. Numerous mechanisms have been suggested as to how these interventions may lower PSA levels. However, it is possible that the primary mechanism of action is partial androgen suppression and/or estrogen manipulation.

  3. Growth suppression caused by corticosteroid eye drops.

    PubMed

    Wolthers, Ole D

    2011-01-01

    Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

  4. Suppression subtractive hybridization.

    PubMed

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  5. Innovative Strategy for Treatment of Lung Cancer: Inhalatory Codelivery of Anticancer Drugs and siRNA for Suppression of Cellular Resistance

    DTIC Science & Technology

    2011-07-01

    will allow for experimental assessment of pump suppression by the proposed DDS. Additionally, recent clinical studies demonstrated that combinations...cancer cells. Our previous study demonstrated that the receptors for LHRH peptide are overexpressed in cancer cells and are not expressed detectably...fluorescence of DOX was employed in this study to evaluate a release of the drugs from LHRH-PEG-siRNA-Drug-MSNs complex. Briefly, the release of DOX from

  6. Ammonium treatments to suppress toxic blooms of Prymnesium parvum in a subtropical lake of semi-arid climate: results from in situ mesocosm experiments.

    PubMed

    Grover, James P; Roelke, Daniel L; Brooks, Bryan W; Gable, George M; Neisch, Michael T; Hayden, Natanya J; Valenti, Theodore W; Prosser, Krista N; Umphres, George D; Hewitt, Natalie C

    2013-09-01

    Prymnesium parvum is a haptophyte alga that forms toxic, fish-killing blooms in a variety of brackish coastal and inland waters. Its abundance and toxicity are suppressed by ammonium additions in laboratory cultures and aquaculture ponds. In a cove of a large reservoir (Lake Granbury, Texas, USA) with recurring, seasonal blooms of P. parvum, ammonium additions were tested in mesocosm enclosures for their ability to suppress blooms and their effects on non-target planktonic organisms. One experiment occurred prior to the peak abundance of a P. parvum bloom in the cove, and one encompassed the peak abundance and decline of the bloom. During 21-day experiments, weekly doses raised ammonium concentrations by either 10 or 40 μM. The added ammonium accumulated in experimental mesocosms, with little uptake by biota or other losses. Effects of ammonium additions generally increased over the course of the experiments. The higher ammonium dose suppressed the abundance and toxicity of P. parvum. The biomass of non-haptophyte algae was stimulated by ammonium additions, while positive, negative and neutral effects on zooplankton taxa were observed. Low ammonium additions insufficient to control P. parvum exacerbated its harmful effects. Our results indicate a potential for mitigating blooms of P. parvum with sufficient additions of ammonium to coves of larger lakes. However, factors excluded from mesocosms, such as dilution of ammonium by water exchange and sediment ammonium uptake, could reduce the effectiveness of such additions, and they would entail a risk of eutrophication from the added nitrogen.

  7. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  8. Effects of tic suppression: ability to suppress, rebound, negative reinforcement, and habituation to the premonitory urge.

    PubMed

    Specht, Matt W; Woods, Douglas W; Nicotra, Cassandra M; Kelly, Laura M; Ricketts, Emily J; Conelea, Christine A; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2013-01-01

    The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

  9. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  10. Yeast-Derived Particulate β-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer.

    PubMed

    Albeituni, Sabrin H; Ding, Chuanlin; Liu, Min; Hu, Xiaoling; Luo, Fengling; Kloecker, Goetz; Bousamra, Michael; Zhang, Huang-ge; Yan, Jun

    2016-03-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80(+)CD11c(+) cells in vitro that served as potent APC to induce Ag-specific CD4(+) and CD8(+) T cell responses in a dectin-1-dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c(+) cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non-small cell lung carcinoma that had received WGP treatment for 10-14 d prior to any other treatment had a decreased frequency of CD14(-)HLA-DR(-)CD11b(+)CD33(+) MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer.

  11. Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm.

    PubMed

    Jongen, Lynn; Paridaens, Robert; Floris, Giuseppe; Wildiers, Hans; Neven, Patrick

    2016-02-01

    We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a 'triple-negative' status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.3. Our observation demonstrates that an AR-expressing apocrine breast cancer may respond to androgen deprivation, as an ER-positive breast cancer may benefit from estrogen deprivation. It highlights the importance of further research targeting the AR pathway in apocrine carcinoma, for which androgens represent the sole (known) steroid hormone stimulating tumor growth. Future clinical trials should not only focus on AR inhibitors like enzalutamide, but also on ablative modalities like low-dose hydrocortisone aiming at medical adrenalectomy. This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity.

  12. Repeated 100 Hz TENS for the Treatment of Chronic Inflammatory Hyperalgesia and Suppression of Spinal Release of Substance P in Monoarthritic Rats

    PubMed Central

    Liu, Hong-Xiang; Tian, Jin-Bin; Luo, Fei; Jiang, Yu-Hui; Deng, Zu-Guo; Xiong, Liang; Liu, Cheng; Wang, Jin-Shu

    2007-01-01

    Transcutaneous electrical nerve stimulation (TENS) has been shown to be an effective measure for pain relief. The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP) release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra-articular injection of complete Freund's adjuvant (CFA) at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks) of monoarthritis, twice-a-week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4–9 weeks), however, once-a-week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice- or five-times-a-week schedule. Using three levels of intensity of TENS, we found that the weaker (1-1-2 mA) stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i) consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii) for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii) a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia. PMID:17342243

  13. Assessment of the Safety and Efficacy of a Raft-Forming Alginate Reflux Suppressant (Liquid Gaviscon) for the Treatment of Heartburn during Pregnancy.

    PubMed

    Strugala, Vicki; Bassin, Julian; Swales, Valerie S; Lindow, Stephen W; Dettmar, Peter W; Thomas, Edward C M

    2012-01-01

    Gastro-oesophageal reflux (GER) and the symptoms of heartburn and regurgitation are common in pregnancy. These symptoms are transient and mostly resolve postpartum but have a negative impact on quality of life. Here, we present a prospective clinical evaluation of the safety and efficacy of an alginate raft-forming oral suspension that is licensed for use in pregnancy. The study was a multicentre, prospective, open-label, and baseline-controlled study of Liquid Gaviscon (LG) in the treatment of heartburn in pregnant women with current symptoms of heartburn and/or reflux requiring treatment (recruited 144). The efficacy of the study medication was rated by the investigator (primary endpoint) and patient. Treatment was deemed to be a success in 91% of patients as judged by the investigator (95% CI 85.0-95.3) and 90% (95% CI 84.1-94.8) when assessed by the patient themselves. Very few adverse events or serious adverse events were reported that were considered to be related to the study medication, and these were consistent with the normal population incidences. Serum sodium levels remained unchanged. This prospective open-label study in a large number of pregnant women has shown that LG is both safe and highly efficacious in the treatment of heartburn and GER symptoms in pregnancy.

  14. Long-term nicotine treatment suppresses IL-1β release and attenuates substance P- and 5-HT-evoked Ca²⁺ responses in astrocytes.

    PubMed

    Westerlund, Anna; Björklund, Ulrika; Rönnbäck, Lars; Hansson, Elisabeth

    2013-10-11

    The aim of this study was to investigate whether short- or long-term nicotine treatment, had an influence on Ca(2+)-induced intracellular Ca(2+) release in astrocytes co-cultured with microvascular endothelial cells, and if the release of interleukin-1β (IL-1β) changed during this treatment. We found that nicotine-evoked Ca(2+) transients were not attenuated up to 10d of incubation with nicotine, neither was the α7-nicotine acetylcholine receptor (α7-nAChR) protein. After 10d the IL-1β release was decreased. Furthermore, substance P- and 5-hydroxytryptamine (5-HT)-evoked Ca(2+) transients were attenuated after 10d of nicotine treatment, but glial cell line-derived neurotrophic factor (GDNF) had no effect on these transients. The results show that long-term nicotine treatment had no influence on nicotine-evoked Ca(2+) transients or protein expression of the α7-nAChR, but had with a decreased IL-1β release. The Gq protein and inositoltrisphosphate system seems to be influenced by the attenuation of Ca(2+)-evoked intracellular Ca(2+) release after stimulation with substance P and 5-HT.

  15. Suppression of volatile production in tomato fruit exposed to chilling temperature and alleviation of chilling injury by a pre-chilling heat treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chilling exposure of tomato fruit to 5 °C for less than 5 days at mature green stage does not cause visual symptom of chilling injury (CI), however, it is unknown whether such conditions would impact flavor quality (internal CI) after ripening, and if a pre-chilling heat treatment could alleviate in...

  16. Assessment of the Safety and Efficacy of a Raft-Forming Alginate Reflux Suppressant (Liquid Gaviscon) for the Treatment of Heartburn during Pregnancy

    PubMed Central

    Strugala, Vicki; Bassin, Julian; Swales, Valerie S.; Lindow, Stephen W.; Dettmar, Peter W.; Thomas, Edward C. M.

    2012-01-01

    Gastro-oesophageal reflux (GER) and the symptoms of heartburn and regurgitation are common in pregnancy. These symptoms are transient and mostly resolve postpartum but have a negative impact on quality of life. Here, we present a prospective clinical evaluation of the safety and efficacy of an alginate raft-forming oral suspension that is licensed for use in pregnancy. The study was a multicentre, prospective, open-label, and baseline-controlled study of Liquid Gaviscon (LG) in the treatment of heartburn in pregnant women with current symptoms of heartburn and/or reflux requiring treatment (recruited 144). The efficacy of the study medication was rated by the investigator (primary endpoint) and patient. Treatment was deemed to be a success in 91% of patients as judged by the investigator (95% CI 85.0–95.3) and 90% (95% CI 84.1–94.8) when assessed by the patient themselves. Very few adverse events or serious adverse events were reported that were considered to be related to the study medication, and these were consistent with the normal population incidences. Serum sodium levels remained unchanged. This prospective open-label study in a large number of pregnant women has shown that LG is both safe and highly efficacious in the treatment of heartburn and GER symptoms in pregnancy. PMID:23209926

  17. Hail suppression and society.

    PubMed

    Changnon, S A; Farhar, B C; Swanson, E R

    1978-04-28

    An interdisciplinary assessment of hail suppression in the past, present, and future has shown it to be currently scientifically uncertain but a potentially beneficial future technology. An established suppression technology would be widely adopted in the Great Plains, providing benefits to agriculture and secondarily to the American consumer. Development of a reliable technology will require a sizable longterm federal commitment to atmospheric and social research. Subcritical funding would be a mistake. Orderly future usage of hail suppression, with its scientific complexities and regional character, will necessitate development of governmental regulations, evaluation procedures, interstate arrangements, and means for compensating those who lose from modification.

  18. Repeated Baclofen treatment ameliorates motor dysfunction, suppresses reflex activity and decreases the expression of signaling proteins in reticular nuclei and lumbar motoneurons after spinal trauma in rats.

    PubMed

    Kucharíková, Andrea; Schreiberová, Andrea; Závodská, Monika; Gedrová, Štefánia; Hricová, Ľudmila; Pavel, Jaroslav; Gálik, Ján; Maršala, Martin; Lukáčová, Nadežda

    2014-03-01

    The interruption of supraspinal input to the spinal cord leads to motor dysfunction and the development of spasticity. Clinical studies have shown that Baclofen (a GABAB agonist), while effective in modulating spasticity is associated with side-effects and the development of tolerance. The aim of the present study was to assess if discontinued Baclofen treatment and its repeated application leads antispasticity effects, and whether such changes affect neuronal nitric oxide synthase (nNOS) in the brainstem, nNOS and parvalbumin (PV) in lumbar α-motoneurons and glial fibrillary acidic protein in the ventral horn of the spinal cord. Adult male Wistar rats were exposed to Th9 spinal cord transection. Baclofen (30mg/b.w.) diluted in drinking water, was administered for 6 days, starting at week 1 after injury and then repeated till week 4 after injury. The behavior of the animals was tested (tail-flick test, BBB locomotor score) from 1 to 8 weeks. Our results clearly indicate the role of nitric oxide, produced by nNOS in the initiation and the maintenance of spasticity states 1, 6 and 8 weeks after spinal trauma. A considerable decrease of nNOS staining after Baclofen treatment correlates with improvement of motor dysfunction. The findings also show that parvalbumin and astrocytes participate in the regulation of ion concentrations in the sub-acute phase after the injury.

  19. Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice

    PubMed Central

    Bouike, Go; Nishitani, Yosuke; Shiomi, Hideyuki; Yoshida, Masaru; Azuma, Takeshi; Hashimoto, Takashi; Kanazawa, Kazuki; Mizuno, Masashi

    2011-01-01

    To clarify the mechanism of the antiallergic activity of Agaricus blazei Murill extract (ABME), the present paper used an in vivo allergy model and an in vitro intestinal gut model. During OVA sensitization, the serum IgE levels decreased significantly in ABME group. Interleukin (IL)-4 and -5 produced from OVA-restimulated splenocytes was significantly decreased, and anti-CD3ε/CD28 antibody treatment also reduced IL-10, -4, and -5 production and increased IFN-γ production in ABME group. These results suggest that oral administration of ABME improves Th1/Th2 balance. Moreover, a coculture system constructed of Caco-2 cells and splenocytes from OT-II mice or RAW 264.7 cells indicated that the significant increases in IFN-γ production by ABME treatment. Therefore, it was concluded that the antiallergic activity of ABME was due to the activation of macrophages by epithelial cells and the promotion of the differentiation of naïve T cells into Th1 cells in the immune. PMID:20953432

  20. Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non-small-cell lung cancer cells.

    PubMed

    Lin, Hui-Ping; Kuo, Li-Kuo; Chuu, Chih-Pin

    2012-01-01

    Curcumin (diferuloylmethane) is a phenolic compound present in turmeric and is ingested daily in many parts of the world. Curcumin has been reported to cause inhibition on proliferation and induction of apoptosis in many human cancer cell lines, including non-small cell lung cancer cells (NSCLC). However, the clinical application of curcumin is restricted by its low bioavailability. In this report, it was observed that combined treatment of a low dosage of curcumin (5-10 µM) with a low concentration (0.1-2.5 µM) of small molecule inhibitors, including AG1478, AG1024, PD173074, LY294002 and caffeic acid phenethyl ester (CAPE) increased the growth inhibition in two human NSCLC cell lines: A549 and H1299 cells. The observation suggested that combined treatment of a low dosage of curcumin with inhibitors against epidermal growth factor receptor (EGFR), insulin-like growth factor 1 (IGF-1R), fibroblast growth factors receptor (FGFR), phosphatidylinositol 3-kinases (PI3K) or NF-κB signaling pathway may be a potential adjuvant therapy beneficial to NSCLC patients.

  1. Growth hormone suppression test

    MedlinePlus

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... At least 3 blood samples are taken. The test is done in the following way: The first blood sample is collected between 6 ...

  2. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  3. Pharmacological suppression of the Ras/MAPK pathway in thyroid carcinoma cells can provoke opposite effects on cell migration and proliferation: The appearance of yin-yang effects and the need of combinatorial treatments.

    PubMed

    Glassmann, Alexander; Winter, Jochen; Kraus, Dominik; Veit, Nadine; Probstmeier, Rainer

    2014-12-01

    A major challenge in tumor therapy is the decrease or even the halting of cell proliferation and migration of cancerous cells. In the present study, we have analyzed the impact of a pharmacological blockade of the PI3K/Akt and MAPK/ERK1/2 signaling pathways on cell migration, proliferation and cell death in three human thyroid tumor cell lines that represent the main types of malignant thyroid carcinomas (B-CPAP, follicular; Cal-62, anaplastic; FTC-133, papillary thyroid carcinoma cells) and in which these pathways are constitutively activated. In general, pharmacological perturbation of PI3/Akt (application of MK-2206) and MEK/ERK1/2 (application of PD0325901 or U0126) signaling led to a cell line and drug-specific decrease in the proliferation and migration potential of thyroid carcinoma cells, although to a varying extent. However, one exception became apparent: in Cal-62 cells inhibition of the MEK/ERK1/2 module increased the migration rate up to 50%. This effect could be prevented by a simultaneous suppression of the PI3/Akt pathway, but also by application of the multiple kinase inhibitor sorafenib, a treatment that did not change the activation state of Akt. Thus, a pharmacological perturbation of canonical signaling pathways in thyroid carcinoma may induce drug-dependent yin-yang effects that are characterized by a simultaneous suppression of one (i.e., proliferation) and the activation of another (i.e., migration) cellular process. The appearance of such phenomena should be taken into account when therapy plans are established.

  4. Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways

    PubMed Central

    Zhao, L.M.; Pang, A.X.

    2017-01-01

    Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways. PMID:28099584

  5. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    PubMed Central

    Lin, Ching-Lung; Wang, Sheue-Er; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Cardiac failure is often observed in aging patients with Huntington’s disease (HD). However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT) were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01). Cardiac expressions of superoxide dismutase 2 (SOD2) and B-cell lymphoma 2 (Bcl-2) in aging R6/2 HD mice were significantly lower than their WT (P<0.01), but cardiac expressions of tumor necrosis factor alpha (TNF-α), neurotrophin-3 (3-NT), 4-hydroxynonenal (4-HNE), Bcl-2-associated X protein (Bax), calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05). Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05). Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01), but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly reduced under oral B307 treatment (P<0.05). Oral B307 treatment may briefly alleviate cardiac failure in aging HD R6/2 mice via suppressing cardiac oxidative stress, inflammation, and apoptosis. We suggested that the herbal formula B307 may be further developed as a potential health supplement for ameliorating cardiac failure associated with

  6. Detection and Description of Soils with Specific Nematode Suppressiveness

    PubMed Central

    Westphal, Andreas

    2005-01-01

    Soils with specific suppressiveness to plant-parasitic nematodes are of interest to define the mechanisms that regulate population density. Suppressive soils prevent nematodes from establishing and from causing disease, and they diminish disease severity after initial nematode damage in continuous culturing of a host. A range of non-specific and specific soil treatments, followed by infestation with a target nematode, have been employed to identify nematode-suppressive soils. Biocidal treatments, soil transfer tests, and baiting approaches together with observations of the plant-parasitic nematode in the root zone of susceptible host plants have improved the understanding of nematode-suppressive soils. Techniques to demonstrate specific soil suppressiveness against plant-parasitic nematodes are compared in this review. The overlap of studies on soil suppressiveness with recent advances in soil health and quality is briefly discussed. The emphasis is on methods (or criteria) used to detect and identify soils that maintain specific soil suppressiveness to plant-parasitic nematodes. While biocidal treatments can detect general and specific soil suppressiveness, soil transfer studies, by definition, apply only to specific soil suppressiveness. Finally, potential strategies to exploit suppressive soils are presented. PMID:19262851

  7. PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin.

    PubMed

    Vu, John P; Goyal, Deepinder; Luong, Leon; Oh, Suwan; Sandhu, Ravneet; Norris, Joshua; Parsons, William; Pisegna, Joseph R; Germano, Patrizia M

    2015-11-15

    Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1-/-) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP1-38 or PACAP1-27 before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP1-38 administration in fasted WT mice. PACAP1-38/PACAP1-27 injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP1-38 injected into PAC1-/- mice failed to significantly change food intake. Importantly, PACAP1-38 reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1-/- mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP1-38/PACAP1-27 significantly reduced appetite and food intake through PAC1. In PAC1-/- mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.

  8. Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis.

    PubMed

    Antoniali, Giulia; Marcuzzi, Federica; Casarano, Elena; Tell, Gianluca

    2015-11-01

    Cadmium (Cd) is a carcinogenic and neurotoxic environmental pollutant. Among the proposed mechanisms for Cd toxic effects, its ability to promote oxidative stress and to inhibit, in vitro, the activities of some Base Excision DNA Repair (BER) enzymes, such as hOGG1, XRCC1 and APE1, have been already established. However, the molecular mechanisms at the basis of these processes are largely unknown especially at sub-lethal doses of Cd and no information is available on the effect of Cd on the expression levels of BER enzymes. Here, we show that non-toxic treatment of neuronal cell lines, with pro-mitogenic doses of Cd, promotes a significant time- and dose-dependent down-regulation of DNA polymerase δ (POLD1) expression through a transcriptional mechanism with a modest effect on Polβ, XRCC1 and APE1. We further elucidated that the observed transcriptional repression on Polδ is acted by through competition by activated p53 on Sp1 at POLD1 promoter and by a squelching effect. We further proved the positive effect of Sp1 not only on POLD1 expression but also on Polβ, XRCC1 and APE1 expression, suggesting that Sp1 has pleiotropic effects on the whole BER pathway. Our results indicated that Cd-mediated impairment of BER pathway, besides acting on the enzymatic functions of some key proteins, is also exerted at the gene expression level of Polδ by acting on the p53-Sp1 regulatory axis. These data may explain not only the Cd-induced neurotoxic effects but also the potential carcinogenicity of this heavy metal.

  9. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  10. Sensory suppression during feeding

    PubMed Central

    Foo, H.; Mason, Peggy

    2005-01-01

    Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors. PMID:16275919

  11. Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1+ patients

    PubMed Central

    Papasavvas, Emmanouil; Foulkes, Andrea; Yin, Xiangfan; Joseph, Jocelin; Ross, Brian; Azzoni, Livio; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

    2015-01-01

    The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1+ patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3+ CD4− perforin+ IFN-γ+ cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R2 = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3+ CD4− CSFElo CD107a+ cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies. PMID:25684333

  12. Corticosteroids and Immune Suppressive Therapies in Horses.

    PubMed

    Leclere, Mathilde

    2017-04-01

    Immune suppressive therapies target exaggerated and deleterious responses of the immune system. Triggered by exogenous or endogenous factors, these improper responses can lead to immune or inflammatory manifestations, such as urticaria, equine asthma, or autoimmune and immune-mediated diseases. Glucocorticoids are the most commonly used immune suppressive drugs and the only ones supported by robust evidence of clinical efficacy in equine medicine. In some conditions, combining glucocorticoids with other pharmacologic and nonpharmacologic treatments, such as azathioprine, antihistamine, bronchodilators, environmental management, or desensitization, can help to decrease dosages and associated side effects.

  13. Learning motion discrimination with suppressed and un-suppressed MT.

    PubMed

    Thompson, Benjamin; Liu, Zili

    2006-06-01

    Perceptual learning of motion direction discrimination is generally thought to rely on the middle temporal area of the brain (MT/V5). A recent study investigating learning of motion discrimination when MT was psychophysically suppressed found that learning was possible with suppressed MT, but only when the task was sufficiently easy [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. We investigated whether this effect was indeed due to MT suppression or whether it could be explained by task difficulty alone. By comparing learning of motion discrimination when MT was suppressed vs. un-suppressed, at different task difficulties, we found that task difficulty alone could not explain the effects. At the highest difficulty, learning was not possible with suppressed MT, confirming [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. In comparison, learning was possible with un-suppressed MT at the same difficulty level. At the intermediate task difficulty, there was a clear learning disadvantage when MT was suppressed. Only for the easiest level of difficulty, did learning become equally possible for both suppressed and un-suppressed conditions. These findings suggest that MT plays an important role in learning to discriminate relatively fine differences in motion direction.

  14. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  15. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  16. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  17. Abnormal Grain Growth Suppression in Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  18. Treatment

    MedlinePlus

    ... Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox Vaccine Guidance Infection Control: Hospital Infection Control: Home ... Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections Poxvirus Treatment Recommend on ...

  19. Tactile suppression of displacement.

    PubMed

    Ziat, Mounia; Hayward, Vincent; Chapman, C Elaine; Ernst, Marc O; Lenay, Charles

    2010-10-01

    In vision, the discovery of the phenomenon of saccadic suppression of displacement has made important contributions to the understanding of the stable world problem. Here, we report a similar phenomenon in the tactile modality. When scanning a single Braille dot with two fingers of the same hand, participants were asked to decide whether the dot was stationary or whether it was displaced from one location to another. The stimulus was produced by refreshable Braille devices that have dots that can be swiftly raised and recessed. In some conditions, the dot was stationary. In others, a displacement was created by monitoring the participant's finger position and by switching the dot activation when it was not touched by either finger. The dot displacement was of either 2.5 mm or 5 mm. We found that in certain cases, displaced dots were felt to be stationary. If the displacement was orthogonal to the finger movements, tactile suppression occurred effectively when it was of 2.5 mm, but when the displacement was of 5 mm, the participants easily detected it. If the displacement was medial-lateral, the suppression effect occurred as well, but less often when the apparent movement of the dot opposed the movement of the finger. In such cases, the stimulus appeared sooner than when the brain could predict it from finger movement, supporting a predictive rather than a postdictive differential processing hypothesis.

  20. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  1. Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone.

    PubMed

    Hughes, Sam; Hickey, Louise; Donaldson, Lucy F; Lumb, Bridget M; Pickering, Anthony E

    2015-02-01

    The descending noradrenergic (NAergic) projection to the spinal cord forms part of an endogenous analgesic system. After nerve injury, a localised failure in this compensatory system has been implicated as a permissive factor in the development of neuropathic sensitisation. We investigated whether restoring descending NAergic tone with intrathecal reboxetine can oppose the development of the neuropathic pain phenotype after tibial nerve transection (TNT). Rats had a lumbar intrathecal catheter implanted at the time of nerve injury for administration of reboxetine (10 μg) in both acute and chronic dosing experiments. In acute dosing experiments, both intrathecal and systemic (30 mg/kg) reboxetine partially reversed mechanical allodynia. This antiallodynic effect of intrathecal reboxetine was blocked by prior administration of yohimbine (α2-adrenoceptor antagonist, 30 μg) but not by prazosin (α1-adrenoceptor antagonist, 30 μg) or propranolol (β-adrenoceptor antagonist, 100 μg). Chronic intrathecal reboxetine (10 μg, intrathecally, twice daily for 2 weeks) suppressed the development of cold and mechanical allodynia. Nerve-injured animals demonstrated a place preference for intrathecal reboxetine, suggesting that it also reduced spontaneous pain. In contrast, an equivalent antiallodynic dose of systemic reboxetine (30 mg/kg) was aversive in both naive and TNT rats. On cessation of chronic intrathecal reboxetine, there was a gradual development of allodynic sensitisation that was indistinguishable from control TNT animals by 7 days after the end of dosing. Our results suggest that pharmacological restoration of spinal NAergic tone with intrathecal reboxetine can suppress both allodynia and spontaneous pain in the TNT model.

  2. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  3. Pharmacology of appetite suppression.

    PubMed

    Halford, J C; Blundell, J E

    2000-01-01

    Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i

  4. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  5. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  6. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  7. Ultrasonic Frost Suppression

    NASA Astrophysics Data System (ADS)

    Adachi, Kazunari; Saiki, Kazushi; Sato, Hiroki; Ito, Takahiro

    2003-02-01

    The authors have observed the accumulation of frost on the surface of a rectangular aluminum alloy (duralumin) plate flexurally vibrating at approximately 37 kHz in an atmosphere of almost 100% relative humidity at 2°C. The plate surface, which had been prepolished with abrasive slurry for maintaining its average surface roughness of about 100 nm, was refrigerated at a temperature of -20°C with cold carbon-dioxide gas as coolant. Experiments have been conducted with and without fine silver oxide powder spread on the plate surface so as to examine the effect of artificial ice crystal nuclei. Ultrasonic vibrations with an amplitude of 3.4 μm (rms) are found to suppress frost accumulation by approximately 60%. The phenomenon cannot be ascribed directly to the heat generation caused by high-amplitude vibration, but may have a complex mechanical and/or acoustical effect on small ice crystals.

  8. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  9. The site of saccadic suppression.

    PubMed

    Thilo, Kai V; Santoro, Loredana; Walsh, Vincent; Blakemore, Colin

    2004-01-01

    During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

  10. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  11. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  12. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  13. Painful consequences of anger suppression.

    PubMed

    Quartana, Phillip J; Burns, John W

    2007-05-01

    The authors experimentally examined the effects of anger suppression on pain perception. On the basis of ironic process theory, they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings, thereby contaminating perception of succeeding pain in an anger-congruent manner. Participants were randomly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment. A cold-pressor task followed. Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels, but also rated the anger-specific dimensions of pain uniquely strong. Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain.

  14. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    NASA Astrophysics Data System (ADS)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  15. Suppression of Eimeria tenella sporulation by disinfectants.

    PubMed

    You, Myung-Jo

    2014-08-01

    The disinfectant effects (DEs) of 10 types of chemicals, defined by their ability to destroy or inhibit oocysts and consequently prevent sporulation of Eimeria tenella field isolate, were evaluated in vitro. Correct species assignments and sample purities were confirmed by the singular internal transcribed spacer (ITS)-PCR analysis. A total of 18 treatments were performed, and the disinfection suppression levels were 75.9% for 39% benzene + 22% xylene (1:10 dilution), 85.5% for 30% cresol soup (1:1 dilution), and 91.7% for 99.9% acetic acid (1:2 dilution) group. The results indicate that acetic acid, cresol soup, and benzene+xylene are good candidates for suppression of E. tenella oocyst sporulation.

  16. Appetite suppressants and valvular heart disease.

    PubMed

    Seghatol, Frank F; Rigolin, Vera H

    2002-09-01

    Appetite suppressants fenfluramine, dexfenfluramine, and phentermine have been used alone or in combination as an alternative to diet and surgery in the management of obesity. This therapy was halted in 1997 after reports of valvular lesions affecting almost one third of patients treated with these drugs. Fortunately, most cases of appetite suppressant-related valve disease are mild or moderate and rarely required valve repair or replacement. Follow-up studies have suggested improvement in valvulopathy after discontinuation of the treatment. The mechanism of valve disease induced by these drugs is speculative and may be related to their serotonergic effects. Echocardiographic features are similar to carcinoid heart disease and valvulopathy associated with ergot use. Most cases require only follow-up and endocarditis prophylaxis; surgery is rarely needed.

  17. Ovarian follicular growth suppression by long-term treatment with a GnRH agonist and impact on small follicle number, oocyte yield, and in vitro embryo production in Zebu beef cows.

    PubMed

    Batista, E O S; Vieira, L M; Sá Filho, M F; Dias, E A R; Bayeux, B M; Accorsi, M F; Monteiro, F M; Souza, A H; Baruselli, P S; D'Occhio, M J

    2016-06-01

    The aim of the present study was to evaluate small follicle number, oocyte yield, and in vitro embryo production (IVEP) in Zebu beef cows treated long term with a GnRH agonist to suppress ovarian follicular growth. Nelore (Bos indicus) cows (n = 20) showing regular estrous cycles were randomly assigned to one of two groups: control (n = 10, placebo ear implant without a GnRH agonist); GnRH agonist (n = 10, GnRH agonist ear implant containing 9.4-mg deslorelin). All cows underwent an ovum pick-up (OPU) session 14 days (Day 14) before the start of treatments (Day 0) followed by seven OPU-IVEP procedures at 30-day intervals (Days 0, 30, 60, 90, 120, 150, and 180). Semen from a single batch of a previously tested bull was used for all the IVEP. Cows treated with agonist reported a decrease over time in the proportion of animals with a (CL; P ≤ 0.05) and large follicles (>10 mm, P ≤ 0.05). These cows had a lesser number of medium + large follicles (>5 mm; 1.74 ± 0.5 vs. 4.13 ± 0.5; P ≤ 0.05), greater number of small follicles (2-5 mm; 44.3 ± 2.8 vs. 30.8 ± 1.8; P ≤ 0.05), greater yield of cumulus-oocyte complexes (COCs; 21.0 ± 2.3 vs. 15.6 ± 1.9; P ≤ 0.05), greater proportion of COCs cultured (79.2 vs. 73.9%; P ≤ 0.05), COCs cleaved (10.6 ± 1.5 vs. 6.8 ± 1.1, P ≤ 0.05), and cleaved rate (52.8 vs. 44.3%; P ≤ 0.05) compared with control cows. The number (3.4 ± 0.7 vs. 3.0 ± 0.6; P > 0.05) and proportion (16.5 vs. 19.1%; P > 0.05) of blastocysts produced were similar between agonist and control cows, respectively. The study has shown that Zebu beef cows treated long term with a GnRH agonist had follicular growth restricted to small follicles. This did not compromise the ability of oocytes to undergo IVF and embryonic development.

  18. Currently available cough suppressants for chronic cough.

    PubMed

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

  19. Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases.

    PubMed

    Keeling, Kim M; Bedwell, David M

    2011-01-01

    Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy.

  20. Suppressing bullfrog larvae with carbon dioxide

    USGS Publications Warehouse

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  1. Simple suppression of radiation damping.

    PubMed

    Khitrin, A K; Jerschow, Alexej

    2012-12-01

    Radiation damping is known to cause line-broadening and frequency shifts of strong resonances in NMR spectra. While several techniques exist for the suppression of these effects, many require specialized hardware, or are only compatible with the presence of few strong resonances. We describe a simple pulse sequence for radiation damping suppression in spectra with many strong resonances. The sequence can be used as-is to generate simple spectra or as a signal excitation part in more advanced experiments.

  2. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  3. Bacterial rRNA Genes Associated with Soil Suppressiveness against the Plant-Parasitic Nematode Heterodera schachtii

    PubMed Central

    Yin, Bei; Valinsky, Lea; Gao, Xuebiao; Becker, J. Ole; Borneman, James

    2003-01-01

    The goal of this study was to identify bacteria involved in soil suppressiveness against the plant-parasitic nematode Heterodera schachtii. Since H. schachtii cysts isolated from the suppressive soil can transfer this beneficial property to nonsuppressive soils, analysis of the cyst-associated microorganisms should lead to the identification of the causal organisms. Our experimental approach was to identify bacterial rRNA genes (rDNA) associated with H. schachtii cysts obtained from soil mixtures with various levels of suppressiveness. We hypothesized that we would be able to identify bacteria involved in the suppressiveness by correlating population shifts with differing levels of suppressiveness. Soil treatments containing different amounts of suppressive and fumigation-induced nonsuppressive soils exhibited various levels of suppressiveness after two nematode generations. The 10%-suppressive-soil treatment contained numbers of eggs per gram of soil similar to those of the 100%-suppressive-soil treatment, indicating that the suppressive factor(s) had been transferred. Bacterial rDNA associated with H. schachtii cysts were identified using a culture-independent method termed oligonucleotide fingerprinting of rRNA genes. Bacteria from five major taxonomic groups (Actinobacteria, Cytophaga-Flexibacter-Bacteroides, α-Proteobacteria, β-Proteobacteria, and γ-Proteobacteria) were identified. Three bacterial rDNA groups contained clones that were more prevalent in the highly suppressive soil treatments than in the less suppressive treatments, indicating a potential involvement in the H. schachtii suppressiveness. When these three groups were examined with specific PCR analyses performed on H. schachtii cysts that developed in soils treated with three biocidal compounds, only one bacterial rDNA group with moderate to high sequence identity to rDNA from several Rhizobium species and uncultured α-proteobacterial clones was consistently associated with the highly

  4. Binocular vision in amblyopia: structure, suppression and plasticity.

    PubMed

    Hess, Robert F; Thompson, Benjamin; Baker, Daniel H

    2014-03-01

    The amblyopic visual system was once considered to be structurally monocular. However, it now evident that the capacity for binocular vision is present in many observers with amblyopia. This has led to new techniques for quantifying suppression that have provided insights into the relationship between suppression and the monocular and binocular visual deficits experienced by amblyopes. Furthermore, new treatments are emerging that directly target suppressive interactions within the visual cortex and, on the basis of initial data, appear to improve both binocular and monocular visual function, even in adults with amblyopia. The aim of this review is to provide an overview of recent studies that have investigated the structure, measurement and treatment of binocular vision in observers with strabismic, anisometropic and mixed amblyopia.

  5. Suppression of autophagy exacerbates Mefloquine-mediated cell death.

    PubMed

    Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Kim, Eun Sung; Kang, Hee; Park, Ji-Ho; Lee, Eunjoo H; Cho, Dong-Hyung

    2012-05-02

    Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.

  6. Local cortical dynamics of burst suppression in the anaesthetized brain.

    PubMed

    Lewis, Laura D; Ching, Shinung; Weiner, Veronica S; Peterfreund, Robert A; Eskandar, Emad N; Cash, Sydney S; Brown, Emery N; Purdon, Patrick L

    2013-09-01

    , subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.

  7. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery.

  8. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  9. Design and performance of duct acoustic treatment

    NASA Technical Reports Server (NTRS)

    Motsinger, R. E.; Kraft, R. E.

    1991-01-01

    The procedure for designing acoustic treatment panels used to line the walls of aircraft engine ducts and for estimating the resulting suppression of turbofan engine duct noise is discussed. This procedure is intended to be used for estimating noise suppression of existing designs or for designing new acoustic treatment panels and duct configurations to achieve desired suppression levels.

  10. A Comparison of Urge Intensity and the Probability of Tic Completion During Tic Freely and Tic Suppression Conditions.

    PubMed

    Specht, Matt W; Nicotra, Cassandra M; Kelly, Laura M; Woods, Douglas W; Ricketts, Emily J; Perry-Parrish, Carisa; Reynolds, Elizabeth; Hankinson, Jessica; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2014-03-01

    Tic-suppression-based treatments (TSBTs) represent a safe and effective treatment option for Chronic Tic Disorders (CTDs). Prior research has demonstrated that treatment naive youths with CTDs have the capacity to safely and effectively suppress tics for prolonged periods. It remains unclear how tic suppression is achieved. The current study principally examines how effective suppression is achieved and preliminary correlates of the ability to suppress tics. Twelve youths, ages 10 to 17 years, with moderate-to-marked CTDs participated in an alternating sequence of tic freely and reinforced tic suppression conditions during which urge intensity and tic frequency were frequently assessed. Probability of tics occurring was half as likely following high-intensity urges during tic suppression (31%) in contrast to low-intensity urges during tic freely conditions (60%). Age was not associated with ability to suppress. Intelligence indices were associated with or trended toward greater ability to suppress tics. Attention difficulties were not associated with ability to suppress but were associated with tic severity. In contrast to our "selective suppression" hypothesis, we found participants equally capable of suppressing their tics regardless of urge intensity during reinforced tic suppression. Tic suppression was achieved with an "across-the-board" effort to resist urges. Preliminary data suggest that ability to suppress may be associated with general cognitive variables rather than age, tic severity, urge severity, and attention. Treatment naive youths appear to possess a capacity for robust tic suppression. TSBTs may bolster these capacities and/or enable their broader implementation, resulting in symptom improvement.

  11. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  12. Molecular Modulation of Prefrontal Cortex: Rational Development of Treatments for Psychiatric Disorders

    PubMed Central

    Gamo, Nao J.; Arnsten, Amy F.T.

    2011-01-01

    Dysfunction of the prefrontal cortex (PFC) is a central feature of many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia and bipolar disorder. Thus, understanding molecular influences on PFC function through basic research in animals is essential to rational drug development. In this review, we discuss the molecular signaling events initiated by norepinephrine and dopamine that strengthen working memory function mediated by the dorsolateral PFC under optimal conditions, and weaken working memory function during uncontrollable stress. We also discuss how these intracellular mechanisms can be compromised in psychiatric disorders, and how novel treatments based on these findings may restore a molecular environment conducive to PFC regulation of behavior, thought and emotion. Examples of successful translation from animals to humans include guanfacine for the treatment of ADHD and related PFC disorders, and prazosin for the treatment of PTSD. PMID:21480691

  13. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors.

    PubMed

    Tachibana, Kaori; Matsumoto, Machiko; Togashi, Hiroko; Kojima, Taku; Morimoto, Yuji; Kemmotsu, Osamu; Yoshioka, Mitsuhiro

    2004-03-04

    Pharmacological characteristics of a serotonin (5-HT) and noradrenaline reuptake inhibitor (SNRI), milnacipran, in modulation of the synaptic plasticity were investigated. Milnacipran (30 mg/kg, i.p.) suppressed the long-term potentiation (LTP) in the hippocampal CA1 field of anesthetized rats. Milnacipran-induced suppression was reversed by pretreatment with the selective 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, i.v.) or the alpha1-adrenoceptor antagonist prazosin (1 and 10 microg/rat, i.c.v.). The alpha2-adrenoceptor antagonist idazoxan (5 mg/kg, i.p.) did not influence the milnacipran-induced synaptic responses. These data suggest that the inhibitory effects of milnacipran on LTP induction are mediated via both 5-HT1A receptors and alpha1-adrenoceptors. In other words, functional interaction between the serotonergic and noradrenergic neuronal systems is involved in alteration of the hippocampal synaptic plasticity, which may be implicated in the SNRI-induced therapeutic effect on psychiatric disorders.

  14. Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race

    PubMed Central

    Cetintas, R.; Dickson, D. W.

    2004-01-01

    The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P ≤ 0.01). PMID:19262836

  15. Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race.

    PubMed

    Cetintas, R; Dickson, D W

    2004-12-01

    The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P

  16. Arsenite suppression of BMP signaling in human keratinocytes

    SciTech Connect

    Phillips, Marjorie A.; Qin, Qin; Hu, Qin; Zhao, Bin; Rice, Robert H.

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte

  17. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    PubMed

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

  18. Recent results about fan noise: Its generation, radiation and suppression

    NASA Technical Reports Server (NTRS)

    Feiler, C. E.

    1982-01-01

    Fan noise including its generation, radiation characteristics, and suppression by acoustic treatment is studied. In fan noise generation, results from engine and fan experiments, using inflow control measures to suppress noise sources related to inflow distortion and turbulence, are described. The suppression of sources related to inflow allows the experiments to focus on the fan or engine internal sources. Some of the experiments incorporated pressure sensors on the fan blades to sample the flow disturbances encountered by the blades. From these data some inferences can be drawn about the origins of the disturbances. Also, hot wire measurements of a fan rotor wake field are presented and related to the fan's noise signature. The radiation and the suppression of fan noise are dependent on the acoustic modes generated by the fan. Fan noise suppression and radiation is described by relating these phenomena to the mode cutoff ratio parameter. In addition to its utility in acoustic treatment design and performance prediction, cutoff ratio was useful in developing a simple description of the radiation pattern for broadband fan noise. Some of the findings using the cutoff ratio parameter are presented.

  19. Concurrent Treatment with Taxifolin and Cilostazol on the Lowering of β-Amyloid Accumulation and Neurotoxicity via the Suppression of P-JAK2/P-STAT3/NF-κB/BACE1 Signaling Pathways

    PubMed Central

    Park, Hee Jeong; Shin, Hwa Kyoung; Hong, Ki Whan; Kim, Chi Dae

    2016-01-01

    Taxifolin is a potent flavonoid that exerts anti-oxidative effect, and cilostazol increases intracellular cAMP levels by inhibiting phosphodiesterase 3 that shows antiinflammatory actions. BACE1 (β-site APP cleaving enzyme 1) is the rate-limiting enzyme responsible for the β-cleavage of amyloid precursor proteins to Aβ peptides. In this study, endogenous Aβ and C99 accumulation was explored in N2a Swe cells exposed to 1% FBS medium. Increased Aβ and C99 levels were significantly attenuated by taxifolin alone and in combination with cilostazol. Increased phosphorylated JAK2 at Tyr1007/1008 (P-JAK), phosphorylated STAT3 at Tyr 705 (P-STAT3) expressions and increased expressions of BACE1 mRNA and protein in the activated N2a Swe cells were significantly attenuated by taxifolin (10~50 μM), cilostazol (10~50 μM) alone and in combination at minimum concentrations. In these cells, decreased cytosol IκBα expression was elevated, and increased nuclear NF-κB p65 level and nuclear NF-κB p65 DNA binding activity were significantly reduced by taxifolin and cilostazol in a similar manner. Following STAT3 gene (~70% reduction) knockdown in N2a cells, Aβ-induced nuclear NF-κB and BACE1 expressions were not observed. Taxifolin, cilostazol, or resveratrol significantly stimulated SIRT1 protein expression. In SIRT1 gene-silenced (~50%) N2a cells, taxifolin, cilostazol, and resveratrol all failed to suppress Aβ1-42-stimulated P-STAT3 and BACE1 expression. Consequently, taxifolin and cilostazol were found to significantly decrease lipopolysaccharide (1–10 μg/ml)-induced iNOS and COX-2 expressions, and nitrite production in cultured BV-2 microglia cells and to increase N2a cell viability. In conclusion, taxifolin and cilostazol strongly inhibited amyloidogenesis in a synergistic manner by suppressing P-JAK2/P-STAT3-coupled NF-κB-linked BACE1 expression via the up-regulation of SIRT1. PMID:27977755

  20. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  1. Weed Suppression by Seven Clover Species

    SciTech Connect

    Ross, Shirley M.; King, Jane R.; Izaurralde, R Cesar C.; O'Donovan, John T.

    2001-01-01

    Used as cover crops, clover species may differ in their ability to suppress weed growth. Field trials were conducted in Alberta, Canada to measure the growth of brown mustard [Brassica juncea (L.) Czern.], in mowed and nonmowed production, as influenced by alsike (Trifolium hybridum L.), balansa [T. michelianum Savi var. balansae (Boiss.) Azn.], berseem (T. alexandrinum L.), crimson [T. incarnatum (Boiss.) Azn.], berseem (T. alexandrinum L.), crimson (T. incarnatum L.), Persian (T. resupinatum L.), red (T. pratense L.), and white Dutch (T. repens L.) clover and fall rye (Secale cereale L.). In 1997, clovers reduced mustard biomass in nonmowed treatments by 29% on a high- fertility soil (Typic Cryoboroll) at Edmonton and by 57% on a low- fertility soil (Typic Cryoboralf) at Breton. At Edmonton, nonmowed mustard biomass was reduced by alsike and berseem clover in 1996 and by alsike, balansa, berseem, and crimson clover in 1997. At Breton, all seven clover species suppressed weed biomass. A negative correlation was noted among clover and mustard biomass at Edmonton but not at Breton. The effects of mowing varied with location, timing, and species. Mowing was beneficial to crop/weed proportion at Edmonton but not at Breton. Mowing at early flowering of mustard large-seeded legumes and sweetclover (Melilotus offici) produced greater benefit than mowing at late flowering. With early mowing, all clover species suppressed mustard growth at Edmonton. Clovers reduced mustard regrowth (g plant21 ) and the number of mustard plants producing regrowth. The characteristics of berseem clover (upright growth, long stems, high biomass, and late flowering) would support its use as a cover crop or forage in north-central Alberta.

  2. Mustard seed meal amendments for suppression of Meloidogyne incognita on tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meal is applied to soil as a fertilizer and for suppressing weeds and pathogens. Brassica juncea (Bj) ‘Pacific Gold’ and Sinapis alba (Sa) ‘IdaGold’ seed meals were tested for suppression of Meloidogyne incognita on tomato ‘BHN 444’. In greenhouse trials these treatments (all 0.25% weig...

  3. Examining the relationship between food thought suppression and binge eating disorder.

    PubMed

    Barnes, Rachel D; Masheb, Robin M; White, Marney A; Grilo, Carlos M

    2013-10-01

    Food thought suppression, or purposely attempting to avoid thoughts of food, is related to a number of unwanted eating- and weight-related consequences, particularly in dieting and obese individuals. Little is known about the possible significance of food thought suppression in clinical samples, particularly obese patients who binge eat. This study examined food thought suppression in 150 obese patients seeking treatment for binge eating disorder (BED). Food thought suppression was not associated with binge eating frequency or body mass index but was significantly associated with higher current levels of eating disorder psychopathology and variables pertaining to obesity, dieting, and binge eating.

  4. The Factors Related to CD4+ T-Cell Recovery and Viral Suppression in Patients Who Have Low CD4+ T Cell Counts at the Initiation of HAART: A Retrospective Study of the National HIV Treatment Sub-Database of Zhejiang Province, China, 2014

    PubMed Central

    He, Lin; Pan, Xiaohong; Dou, Zhihui; Huang, Peng; Zhou, Xin; Peng, Zhihang; Zheng, Jinlei; Zhang, Jiafeng; Yang, Jiezhe; Xu, Yun; Jiang, Jun; Chen, Lin; Jiang, Jianmin; Wang, Ning

    2016-01-01

    Background Since China has a unique system of delivering HIV care that includes all patients’ records. The factors related to CD4+ T-cell recovery and viral suppression in patients who have low CD4+ T cell counts at the initiation of HAART are understudied in the China despite subsequent virological suppression (viral load < 50 copies/mL) is unknown. Methods The authors conducted a retrospective cohort study using data from the national HIV treatment sub-database of Zhejiang province to identify records of HIV+ patients. Patient records were included if they were ≥ 16 years of age, had an initial CD4 count < 100 cells/μL, were on continuous HAART for at least one year by the end of December 31, 2014; and achieved and maintained continued maximum virological suppression (MVS) (< 50 copies/ml) by 9 months after starting HAART. The primary endpoint for analysis was time to first CD4+ T cell count recovery (≥ 200, 350, 500 cells/μL). Cox proportional hazard regression was used to identify the risk factors for CD4+ T cell count recovery to key thresholds (200–350, 350–500, ≥ 500 cells/μL) by the time of last clinical follow-up (whichever occurred first), key thresholds (follow-up date for analysis), with patients still unable to reach the endpoints being censored by the end December 31, 2014 (follow-up date for analysis). Results Of the 918 patients who were included in the study, and the median CD4+ T cell count was 39 cells/μL at the baseline. At the end of follow-up, 727 (79.2%), 363 (39.5%) and 149 (16.2%) patients had return to ≥ 200, 350, and 500 cells/μL, respectively. Kaplan-Meier analysis demonstrated that the rate of patients with CD4+ count recovery to ≥ 200, 350, and 500 cells/μL after 1 year on HAART was 43.6, 8.6, and 2.5%, respectively, after 3 years on treatment was 90.8, 46.3, and 17.9%, respectively, and after 5 years on HAART was 97.1, 72.2, and 36.4%, respectively. The median time to return to 200–350, 350–500, ≥ 500cells

  5. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  6. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation.

    PubMed

    Tang, Jun; Lobatto, Mark E; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M; Calcagno, Claudia; Braza, Mounia S; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L; Duivenvoorden, Raphaël; Sager, Hendrik; Astudillo, Yaritzy M; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P; Strijkers, Gustav J; Stroes, Erik S G; Swirski, Filip K; Nahrendorf, Matthias; Fisher, Edward A; Fayad, Zahi A; Mulder, Willem J M

    2015-04-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E deficient mice (Apoe(-/-) ) with advanced atherosclerotic plaques. This resulted in rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an eight-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.

  7. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik B.; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S. G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  8. Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis

    PubMed Central

    Ranjan, Alok; Srivastava, Sanjay K.

    2016-01-01

    Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells with IC50 ranging between 6–7 μM after 24 h of treatment. Significant autophagy was induced by penfluridol treatment in pancreatic cancer cells. Punctate LC3B and autophagosomes staining confirmed autophagy. Inhibiting autophagy by chloroquine, bafilomycin, 3-methyladenine or LC3BsiRNA, significantly blocked penfluridol-induced apoptosis, suggesting that autophagy lead to apoptosis in our model. Penfluridol treatment suppressed the growth of BxPC-3 tumor xenografts by 48% as compared to 17% when treated in combination with chloroquine. Similarly, penfluridol suppressed the growth of AsPC-1 tumors by 40% versus 16% when given in combination with chloroquine. TUNEL staining and caspase-3 cleavage revealed less apoptosis in the tumors from mice treated with penfluridol and chloroquine as compared to penfluridol alone. Penfluridol treatment also suppressed the growth of orthotopically implanted Panc-1 tumors by 80% by inducing autophagy-mediated apoptosis in the tumors. These studies established that penfluridol inhibits pancreatic tumor growth by autophagy-mediated apoptosis. Since penfluridol is already in clinic, positive findings from our study will accelerate its clinical development. PMID:27189859

  9. Efficacy of Paecilomyces lilacinus in Suppressing Rotylenchulus reniformis on Tomato

    PubMed Central

    Walters, S. Alan; Barker, Kenneth R.

    1994-01-01

    Effects of rice-cultured Paecilomyces lilacinus on Rotylenchulus reniformis were studied in both greenhouse and field microplot tests with 'Rutgers' tomato. Numbers of R. reniformis were reduced (P ≤ 0.05) by P. lilacinus, with suppression in the initial greenhouse test ranging from 46 to 48% for two rice + P. lilacinus treatments; the rice-only treatment caused a nonsignificant reduction of 25%. In the second greenhouse test, total R. reniformis numbers were restricted (P ≤ 0.05) by 41% by the rice + P. lilacinus treatment, whereas the rice-only treatment had a slight negative effect (16% inhibition, NS). Total numbers of R. reniformis were suppressed 59 and 36% at midseason and harvest, respectively, in microplots infested with P. lilacinus. The fungus was recovered from egg masses via isolations in the second greenhouse test. Shoot and fruit growth of Rutgers tomato were restricted by R. reniformis in the initial greenhouse test irrespective of P. lilacinus treatment, but this nematode did not affect fresh shoot weights in the second greenhouse test, The nematode also limited shoot growth of Rutgers tomato in microplots, and P. lilacinus suppressed R. reniformis numbers sufficiently to prevent related impairment of shoot and fruit growth. This study indicated that P. lilacinus has detrimental effects on R. reniformis population development under both greenhouse and field microplot conditions. PMID:19279933

  10. Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone

    PubMed Central

    1996-01-01

    An overproduction of proinflammatory cytokines by activated macrophages/monocytes mediates the injurious sequelae of inflammation, septic shock, tissue injury, and cachexia. We recently synthesized a tetravalent guanylhydrazone compound (CNI-1493) that inhibits cytokine- inducible arginine transport and nitric oxide (NO) production in macrophages, and protects mice against lethal endotoxemia and carrageenan-induced inflammation. During these investigations we noticed that CNI-1493 effectively prevented lipopolysaccharide (LPS)- induced NO production, even when added in concentrations 10-fold less than required to competitively inhibit L-arginine uptake, suggesting that the suppressive effects of this guanylhydrazone compound might extend to other LPS-induced responses. Here, we report that CNI-1493 suppressed the LPS-stimulated production of proinflammatory cytokines (tumor necrosis factor [TNF], interleukins 1beta and 6, macrophage inflammatory proteins 1alpha and 1beta) from human peripheral blood mononuclear cells. Cytokine suppression was specific, in that CNI-1493 did not inhibit either the constitutive synthesis of transforming growth factor beta or the upregulation of major histocompatibility complex class II by interferon gamma (IFN-gamma). In contrast to the macrophage suppressive actions of dexamethasone, which are overridden in the presence of IFN-gamma, CNI-1493 retained its suppressive effects even in the presence of IFN-gamma. The mechanism of cytokine- suppressive action by CNI-1493 was independent of extracellular L- arginine content and NO production and is not restricted to induction by LPS. As a selective inhibitor of macrophage activation that prevents TNF production, this tetravalent guanylhydrazone could be useful in the development of cytokine-suppressive agents for the treatment of diseases mediated by overproduction of cytokines. PMID:8642296

  11. Suppressive effects of ketamine on macrophage functions

    SciTech Connect

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2005-04-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.

  12. Detection of Burst Suppression Patterns in EEG Using Recurrence Rate

    PubMed Central

    Ren, Yongshao; Sleigh, Jamie; Li, Xiaoli

    2014-01-01

    Burst suppression is a unique electroencephalogram (EEG) pattern commonly seen in cases of severely reduced brain activity such as overdose of general anesthesia. It is important to detect burst suppression reliably during the administration of anesthetic or sedative agents, especially for cerebral-protective treatments in various neurosurgical diseases. This study investigates recurrent plot (RP) analysis for the detection of the burst suppression pattern (BSP) in EEG. The RP analysis is applied to EEG data containing BSPs collected from 14 patients. Firstly we obtain the best selection of parameters for RP analysis. Then, the recurrence rate (RR), determinism (DET), and entropy (ENTR) are calculated. Then RR was selected as the best BSP index one-way analysis of variance (ANOVA) and multiple comparison tests. Finally, the performance of RR analysis is compared with spectral analysis, bispectral analysis, approximate entropy, and the nonlinear energy operator (NLEO). ANOVA and multiple comparison tests showed that the RR could detect BSP and that it was superior to other measures with the highest sensitivity of suppression detection (96.49%, P = 0.03). Tracking BSP patterns is essential for clinical monitoring in critically ill and anesthetized patients. The purposed RR may provide an effective burst suppression detector for developing new patient monitoring systems. PMID:24883378

  13. Ribavirin efficiently suppresses porcine nidovirus replication.

    PubMed

    Kim, Youngnam; Lee, Changhee

    2013-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.

  14. Nonsense Suppression as an Approach to Treat Lysosomal Storage Diseases

    PubMed Central

    Keeling, Kim M.

    2016-01-01

    In-frame premature termination codons (PTCs) (also referred to as nonsense mutations) comprise ~10% of all disease-associated gene lesions. PTCs reduce gene expression in two ways. First, PTCs prematurely terminate translation of an mRNA, leading to the production of a truncated polypeptide that often lacks normal function and/or is unstable. Second, PTCs trigger degradation of an mRNA by activating nonsense-mediated mRNA decay (NMD), a cellular pathway that recognizes and degrades mRNAs containing a PTC. Thus, translation termination and NMD are putative therapeutic targets for the development of treatments for genetic diseases caused by PTCs. Over the past decade, significant progress has been made in the identification of compounds with the ability to suppress translation termination of PTCs (also referred to as readthrough). More recently, NMD inhibitors have also been explored as a way to enhance the efficiency of PTC suppression. Due to their relatively low threshold for correction, lysosomal storage diseases are a particularly relevant group of diseases to investigate the feasibility of nonsense suppression as a therapeutic approach. In this review, the current status of PTC suppression and NMD inhibition as potential treatments for lysosomal storage diseases will be discussed. PMID:28367323

  15. Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy.

    PubMed

    Nuzzo, V; Lupoli, G; Esposito Del Puente, A; Rampone, E; Carpinelli, A; Del Puente, A E; Oriente, P

    1998-10-01

    Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis. The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in a group of premenopausal women. Forty consecutive patients (mean age +/- SE = 40.95 +/- 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 +/- 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered. In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

  16. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus

    PubMed Central

    Heath, Sonya L.; Sweeton, Bentley; Williams, Kathy; Cunningham, Pamela; Keele, Brandon F.; Sen, Sharon; Palmer, Brent E.; Chomont, Nicolas; Xu, Yongxian; Basu, Rahul; Hellerstein, Michael S.; Kwa, Suefen

    2016-01-01

    GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA) boost vaccine (GOVX-B11), was undertaken in HIV infected participants on antiretroviral treatment (ART) to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI). Nine men who began antiretroviral therapy (ART) within 18 months of seroconversion and had sustained plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine. Trial Registration clinicaltrials.gov NCT01378156 PMID

  17. Suppression of operant vs consummatory behavior.

    PubMed

    DeCosta, M J; Ayres, J J

    1971-07-01

    The magnitude and variability of conditioned suppression of bar pressing and dipper licking were compared. In two steady-state experiments, suppression of bar pressing was more profound and more stable from day to day. The two measures of suppression were uncorrelated as indexed by Pearson product-moment correlation coefficients computed for adjacent trials. Correlations within measures (internal consistency) were somewhat higher for the bar-press system except when a high proportion of rats completely suppressed on one of the correlated trials. In a transient state experiment in which possible adventitious punishment of both response systems was eliminated, suppression of bar pressing was again more profound and considerably slower to extinguish.

  18. Fire suppression and detection equipment

    SciTech Connect

    E.E. Bates

    2006-01-15

    Inspection and testing guidelines go beyond the 'Code of Federal Regulation'. Title 30 of the US Code of Federal Regulations (30 CFR) contains requirements and references to national standards for inspection, testing and maintenance of fire suppression and detection equipment for mine operators. However, federal requirements have not kept pace with national standards and best practices. The article lists National Fire Protection (NFPA) standards that are referenced by the US Mine Safety and Health Administration (MSHA) in 30 CFR. It then discusses other NFPA Standards excluded from 30 CFR and explains the NFPA standard development process. 2 refs., 3 tabs., 5 photos.

  19. Menstrual suppression in special circumstances.

    PubMed

    Kirkham, Yolanda A; Ornstein, Melanie P; Aggarwal, Anjali; McQuillan, Sarah; Allen, Lisa; Millar, Debra; Dalziel, Nancy; Gascon, Suzy; Hakim, Julie; Ryckman, Julie; Spitzer, Rachel; Van Eyk, Nancy

    2014-10-01

    Objectif : Offrir, aux fournisseurs de soins de santé, un document de consensus canadien comptant des recommandations pour ce qui est de la suppression menstruelle chez les patientes qui font face à des obstacles physiques et/ou cognitifs ou chez les patientes qui font l’objet d’un traitement contre le cancer et pour lesquelles les règles pourraient exercer un effet délétère sur la santé. Options : Le présent document analyse les options disponibles aux fins de la suppression menstruelle, les indications, les contre-indications et les effets indésirables (tant immédiats qu’à long terme) propres à cette dernière, et les explorations et le monitorage nécessaires tout au long de la suppression. Issues : Les cliniciens seront mieux renseignés au sujet des options et des indications propres à la suppression menstruelle chez les patientes qui présentent des déficiences cognitives et/ou physiques et chez les patientes qui font l’objet d’une chimiothérapie, d’une radiothérapie ou d’autres traitements contre le cancer. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, EMBASE, OVID et The Cochrane Library au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « heavy menstrual bleeding », « menstrual suppression », « chemotherapy/radiation », « cognitive disability », « physical disability », « learning disability »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés, aux études observationnelles et aux études pilotes. Aucune restriction n’a été imposée en matière de langue ou de date. Les recherches ont été mises à jour de façon régulière et du nouveau matériel a été intégré à la directive clinique jusqu’en septembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d

  20. Orientation-tuned suppression in binocular rivalry reveals general and specific components of rivalry suppression.

    PubMed

    Stuit, Sjoerd M; Cass, John; Paffen, Chris L E; Alais, David

    2009-10-16

    During binocular rivalry (BR), conflicting monocular images are alternately suppressed from awareness. During suppression of an image, contrast sensitivity for probes is reduced by approximately 0.3-0.5 log units relative to when the image is in perceptual dominance. Previous studies on rivalry suppression have led to controversies concerning the nature and extent of suppression during BR. We tested for feature-specific suppression using orthogonal rivaling gratings and measuring contrast sensitivity to small grating probes at a range of orientations in a 2AFC orientation discrimination task. Results indicate that suppression is not uniform across orientations: suppression was much greater for orientations close to that of the suppressed grating. The higher suppression was specific to a narrow range around the suppressed rival grating, with a tuning similar to V1 orientation bandwidths. A similar experiment tested for spatial frequency tuning and found that suppression was stronger for frequencies close to that of the suppressed grating. Interestingly, no tuned suppression was observed when a flicker-and-swap paradigm was used, suggesting that tuned suppression occurs only for lower-level, interocular rivalry. Together, the results suggest there are two components to rivalry suppression: a general feature-invariant component and an additional component specifically tuned to the rivaling features.

  1. Suppressed epidemics in multirelational networks

    NASA Astrophysics Data System (ADS)

    Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

    2015-08-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

  2. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  3. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment.

    PubMed

    Qi, Wenqing; Spier, Catherine; Liu, Xiaobing; Agarwal, Amit; Cooke, Laurence S; Persky, Daniel O; Chen, Deyu; Miller, Thomas P; Mahadevan, Daruka

    2013-04-01

    Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin lymphomas (NHL) that carry a poor prognosis and are in need of effective therapies. Alisertib (MLN8237) an investigational agent that inhibits Aurora A Ser/Thr kinase has shown activity in PTCL patients. Here we demonstrate that aurora A and B are highly expressed in T-cell lymphoma cell lines. In PTCL patient samples aurora A was positive in 3 of 24 samples and co-expressed with aurora B. Aurora B was positive in tumor cells in 22 of 32 samples. Of the subtypes of PTCL, aurora B was over-expressed in PTCL (NOS) [73%], T-NHL [100%], ALCL (Alk-Neg) [100%] and AITL [100%]. Treatment with MLN8237 inhibited PTCL cell proliferation in CRL-2396 and TIB-48 cells with an IC50 of 80-100nM. MLN8237 induced endo-reduplication in a dose and time dependent manner in PTCL cell lines leading to apoptosis demonstrated by flow cytometry and PARP-cleavage at concentrations achieved in early phase clinical trials. Moreover, inhibition of HisH3 and aurora A phosphorylation was dose dependent and strongly correlated with endo-reduplication. The data provide a sound rationale for aurora inhibition in PTCL as a therapeutic modality and warrants clinical trial evaluation.

  4. Suppression of human spermatogenesis by testosterone implants.

    PubMed

    Handelsman, D J; Conway, A J; Boylan, L M

    1992-11-01

    Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE

  5. Food thought suppression: a matched comparison of obese individuals with and without binge eating disorder.

    PubMed

    Barnes, Rachel D; Masheb, Robin M; Grilo, Carlos M

    2011-12-01

    Preliminary studies of non-clinical samples suggest that purposely attempting to avoid thoughts of food, referred to as food thought suppression, is related to a number of unwanted eating- and weight-related consequences, particularly in obese individuals. Despite possible implications for the treatment of obesity and eating disorders, little research has examined food thought suppression in obese individuals with binge eating disorder (BED). This study compared food thought suppression in 60 obese patients with BED to an age-, gender-, and body mass index (BMI)-matched group of 59 obese persons who do not binge eat (NBO). In addition, this study examined the associations between food thought suppression and eating disorder psychopathology within the BED and NBO groups and separately by gender. Participants with BED and women endorsed the highest levels of food thought suppression. Food thought suppression was significantly and positively associated with many features of ED psychopathology in NBO women and with eating concerns in men with BED. Among women with BED, higher levels of food thought suppression were associated with higher frequency of binge eating, whereas among men with BED, higher levels of food thought suppression were associated with lower frequency of binge eating. Our findings suggest gender differences in the potential significance of food thought suppression in obese groups with and without co-existing binge eating problems.

  6. Drug-induced graves disease from CTLA-4 receptor suppression.

    PubMed

    Borodic, Gary; Hinkle, David M; Cia, Yihong

    2011-01-01

    Monoclonal antibody, ipilimumab, useful for treatment of metastatic melanoma, blocks CTLA-4 mediated T-cell suppression and can also cause a Graves ophthalmopathy like syndrome. Epidemiologic study has linked variant polymorphisms of CTLA-4 receptor gene to the presence of thyroid eye disease. The combination of these observations suggests CTLA-4 mediated T-cell functions are important to the pathogenesis of thyroid-associated eye disease.

  7. Assessing Suppression in Amblyopic Children With a Dichoptic Eye Chart

    PubMed Central

    Birch, Eileen E.; Morale, Sarah E.; Jost, Reed M.; De La Cruz, Angie; Kelly, Krista R.; Wang, Yi-Zhong; Bex, Peter J.

    2016-01-01

    Purpose Suppression has a key role in the etiology of amblyopia, and contrast-balanced binocular treatment can overcome suppression and improve visual acuity. Quantitative assessment of suppression could have a role in managing amblyopia. We describe a novel eye chart to assess suppression in children. Methods We enrolled 100 children (7–12 years; 63 amblyopic, 25 nonamblyopic with strabismus or anisometropia, 12 controls) in the primary cohort and 22 children (3–6 years; 13 amblyopic, 9 nonamblyopic) in a secondary cohort. Letters were presented on a dichoptic display (5 letters per line). Children wore polarized glasses so that each eye saw a different letter chart. At each position, the identity of the letter and its contrast on each eye's chart differed. Children read 8 lines of letters for each of 3 letter sizes. The contrast balance ratio was the ratio at which 50% of letters seen by the amblyopic eye were reported. Results Amblyopic children had significantly higher contrast balance ratios for all letter sizes compared to nonamblyopic children and controls, requiring 4.6 to 5.6 times more contrast in the amblyopic eye compared to the fellow eye (P < 0.0001). Amblyopic eye visual acuity was correlated with contrast balance ratio (r ranged from 0.49–0.57 for the 3 letter sizes). Change in visual acuity with amblyopia treatment was correlated with change in contrast balance ratio (r ranged from 0.43–0.62 for the 3 letter sizes). Conclusions Severity of suppression can be monitored as part of a routine clinical exam in the management of amblyopia in children. PMID:27784068

  8. Social Mimicry Enhances Mu-Suppression During Action Observation.

    PubMed

    Hogeveen, Jeremy; Chartrand, Tanya L; Obhi, Sukhvinder S

    2015-08-01

    During social interactions, there is a tendency for people to mimic the gestures and mannerisms of others, which increases liking and rapport. Psychologists have extensively studied the antecedents and consequences of mimicry at the social level, but the neural basis of this behavior remains unclear. Many researchers have speculated that mimicry is related to activity in the human mirror system (HMS), a network of parietofrontal regions that are involved in both action execution and observation. However, activity of the HMS during reciprocal social interactions involving mimicry has not been demonstrated. Here, we took an electroencephalographic (EEG) index of mirror activity-mu-suppression during action observation-in a pretest/post-test design with 1 of 3 intervening treatments: 1) social interaction in which the participant was mimicked, 2) social interaction without mimicry, or 3) an innocuous computer task, not involving another human agent. The change in mu-suppression from pre- to post-test varied as a function of the intervening treatment, with participants who had been mimicked showing an increase in mu-suppression during the post-treatment action observation session. We propose that this specific modulation of HMS activity as a function of mimicry constitutes the first direct evidence for mirror system involvement in real social mimicry.

  9. How to suppress undesired synchronization.

    PubMed

    Louzada, V H P; Araújo, N A M; Andrade, J S; Herrmann, H J

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network.

  10. Elastic Suppression of Viscous Fingering

    NASA Astrophysics Data System (ADS)

    Peng, Gunnar; Lister, John

    2016-11-01

    Consider peeling an elastic tape or beam away from a rigid base to which it is stuck by a film of viscous liquid. The peeling motion requires air to invade the viscous liquid and is thus susceptible to the Saffman-Taylor fingering instability. We analyse the fundamental travelling-wave solution and show that the advancing air-liquid interface remains linearly stable at higher capillary numbers than in a standard Hele-Shaw cell. A short-wavelength expansion yields an analytical expression for the growth rate which is valid for all unstable modes throughout the parameter space, allowing us to identify and quantify four distinct physical mechanisms that each help suppress the instability. Applying our method to the experiments by Pihler-Puzovic et al. (2012) reveals that the radial geometry and time-variation stabilize the system further.

  11. How to suppress undesired synchronization

    PubMed Central

    Louzada, V. H. P.; Araújo, N. A. M.; Andrade, J. S.; Herrmann, H. J.

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network. PMID:22993685

  12. Tactile stimulation can suppress visual perception

    PubMed Central

    Ide, Masakazu; Hidaka, Souta

    2013-01-01

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities. PMID:24336391

  13. Tactile stimulation can suppress visual perception.

    PubMed

    Ide, Masakazu; Hidaka, Souta

    2013-12-13

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities.

  14. Treatment of sleep disturbances in posttraumatic stress disorder: a review.

    PubMed

    Schoenfeld, Frank B; Deviva, Jason C; Manber, Rachel

    2012-01-01

    Sleep disturbances are among the most commonly reported posttraumatic stress disorder (PTSD) symptoms. It is essential to conduct a careful assessment of the presenting sleep disturbance to select the optimal available treatment. Cognitive-behavioral therapies (CBTs) are at least as effective as pharmacologic treatment in the short-term and more enduring in their beneficial effects. Cognitive-behavioral treatment for insomnia and imagery rehearsal therapy have been developed to specifically treat insomnia and nightmares and offer promise for more effective relief of these very distressing symptoms. Pharmacotherapy continues to be an important treatment choice for PTSD sleep disturbances as an adjunct to CBT, when CBT is ineffective or not available, or when the patient declines CBT. Great need exists for more investigation into the effectiveness of specific pharmacologic agents for PTSD sleep disturbances and the dissemination of the findings to prescribers. The studies of prazosin and the findings of its effectiveness for PTSD sleep disturbance are examples of studies of pharmacologic agents needed in this area. Despite the progress made in developing more specific treatments for sleep disturbances in PTSD, insomnia and nightmares may not fully resolve.

  15. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    PubMed Central

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Stephen J.

    2016-01-01

    Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Anti-inflammatory effects arose with prolonged (i.e. 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, while silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation. PMID:26186142

  16. Inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.

    PubMed

    Tavis, John E; Wang, Hong; Tollefson, Ann E; Ying, Baoling; Korom, Maria; Cheng, Xiaohong; Cao, Feng; Davis, Katie L; Wold, William S M; Morrison, Lynda A

    2014-12-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family.

  17. Two Techniques For Suppressing Vibrations In Structures

    NASA Technical Reports Server (NTRS)

    Chen, Gun-Shing; Garba, John A.; Wada, Ben K.

    1991-01-01

    Two techniques intended to be used together to suppress vibrations in large, complicated truss structure involve combination of active and passive damping. Based on bridge feedback and criterion for placement of actuators. Research continues to develop system using these and other techniques to suppress vibrations in, and help control shape of, truss structure in outer space that supports precise, segmented reflector of communication antenna. On Earth, developmental techniques applicable to suppression of vibrations in bridges and tall buildings.

  18. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  19. Increased attempts to suppress negative and positive emotions in Borderline Personality Disorder.

    PubMed

    Beblo, Thomas; Fernando, Silvia; Kamper, Pia; Griepenstroh, Julia; Aschenbrenner, Steffen; Pastuszak, Anna; Schlosser, Nicole; Driessen, Martin

    2013-12-15

    Patients with Borderline Personality Disorder (BPD) show evidence of disturbed emotion regulation. In particular, patients may try to suppress their emotions with possibly negative effects on mental health. We investigated the suppression of both negative and positive emotions in BPD patients and healthy participants. Thirty BPD patients and 30 matched healthy controls were assessed for emotion suppression using the Emotion Acceptance Questionnaire (EAQ). In addition, we administered additional questionnaires to validate emotion suppression findings. BPD patients reported increased attempts to suppress both negative and positive emotions. These findings indicate that BPD patients are not simply acting out negative emotions. Therapeutic approaches that focus on emotion acceptance of emotions are supported by our study data. Apart from negative emotions, treatment programs should consider positive emotions as well.

  20. ISS Update: Burning and Suppression of Solids

    NASA Video Gallery

    ISS Update Commentator Pat Ryan interviews Paul Ferkul, Principal Investigator for the Burning and Suppression of Solids (BASS) experiment, about performing combustion experiments in microgravity. ...

  1. Issues in Numerical Simulation of Fire Suppression

    SciTech Connect

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  2. Using unplanned fires to help suppressing future large fires in Mediterranean forests.

    PubMed

    Regos, Adrián; Aquilué, Núria; Retana, Javier; De Cáceres, Miquel; Brotons, Lluís

    2014-01-01

    Despite the huge resources invested in fire suppression, the impact of wildfires has considerably increased across the Mediterranean region since the second half of the 20th century. Modulating fire suppression efforts in mild weather conditions is an appealing but hotly-debated strategy to use unplanned fires and associated fuel reduction to create opportunities for suppression of large fires in future adverse weather conditions. Using a spatially-explicit fire-succession model developed for Catalonia (Spain), we assessed this opportunistic policy by using two fire suppression strategies that reproduce how firefighters in extreme weather conditions exploit previous fire scars as firefighting opportunities. We designed scenarios by combining different levels of fire suppression efficiency and climatic severity for a 50-year period (2000-2050). An opportunistic fire suppression policy induced large-scale changes in fire regimes and decreased the area burnt under extreme climate conditions, but only accounted for up to 18-22% of the area to be burnt in reference scenarios. The area suppressed in adverse years tended to increase in scenarios with increasing amounts of area burnt during years dominated by mild weather. Climate change had counterintuitive effects on opportunistic fire suppression strategies. Climate warming increased the incidence of large fires under uncontrolled conditions but also indirectly increased opportunities for enhanced fire suppression. Therefore, to shift fire suppression opportunities from adverse to mild years, we would require a disproportionately large amount of area burnt in mild years. We conclude that the strategic planning of fire suppression resources has the potential to become an important cost-effective fuel-reduction strategy at large spatial scale. We do however suggest that this strategy should probably be accompanied by other fuel-reduction treatments applied at broad scales if large-scale changes in fire regimes are to be

  3. Bone suppression technique for chest radiographs

    NASA Astrophysics Data System (ADS)

    Huo, Zhimin; Xu, Fan; Zhang, Jane; Zhao, Hui; Hobbs, Susan K.; Wandtke, John C.; Sykes, Anne-Marie; Paul, Narinder; Foos, David

    2014-03-01

    High-contrast bone structures are a major noise contributor in chest radiographic images. A signal of interest in a chest radiograph could be either partially or completely obscured or "overshadowed" by the highly contrasted bone structures in its surrounding. Thus, removing the bone structures, especially the posterior rib and clavicle structures, is highly desirable to increase the visibility of soft tissue density. We developed an innovative technology that offers a solution to suppress bone structures, including posterior ribs and clavicles, on conventional and portable chest X-ray images. The bone-suppression image processing technology includes five major steps: 1) lung segmentation, 2) rib and clavicle structure detection, 3) rib and clavicle edge detection, 4) rib and clavicle profile estimation, and 5) suppression based on the estimated profiles. The bone-suppression software outputs an image with both the rib and clavicle structures suppressed. The rib suppression performance was evaluated on 491 images. On average, 83.06% (±6.59%) of the rib structures on a standard chest image were suppressed based on the comparison of computer-identified rib areas against hand-drawn rib areas, which is equivalent to about an average of one rib that is still visible on a rib-suppressed image based on a visual assessment. Reader studies were performed to evaluate reader performance in detecting lung nodules and pneumothoraces with and without a bone-suppression companion view. Results from reader studies indicated that the bone-suppression technology significantly improved radiologists' performance in the detection of CT-confirmed possible nodules and pneumothoraces on chest radiographs. The results also showed that radiologists were more confident in making diagnoses regarding the presence or absence of an abnormality after rib-suppressed companion views were presented

  4. Attentional selection by distractor suppression.

    PubMed

    Caputo, G; Guerra, S

    1998-03-01

    Selective attention was studied in displays containing singletons popping out for their odd form or color. The target was defined as the form-singleton, the distractor as the color-singleton. The task was to discriminate the length of a longer line inside the target. Target-distractor similarity was controlled using a threshold measurement as dependent variable in experiments in which distractor presence vs absence, bottom-up vs top-down selection (through knowledge of target features), and target-distractor distance were manipulated. The results in the bottom-up condition showed that length threshold was elevated when a distractor was present and that this elevation progressively increased as the number of distractors was increased from one to two. This set-size effect was not accounted by the hypothesis that selective attention intervenes only at the stage of decision before response. Selective attention produced a suppressive surround in which discriminability of neighboring objects was strongly reduced, and a larger surround in which discriminability was reduced by an approximately constant amount. Different results were found in the top-down condition in which target discriminability was unaffected by distractor presence and no effect of target-distractor distance was found. On the other hand, response times in both bottom-up and top-down conditions were slower the shorter the target-distractor distance was. On the basis of the experimental results, selective attention is a parallel process of spatial filtering at an intermediate processing level operating after objects have been segmented. This filtering stage explores high level interactions between objects taking control on combinatorial explosion by operating over only a limited spatial extent: it picks out a selected object and inhibits the neighboring objects; then, non-selected objects are suppressed across the overall image. When no feature-based selection is available in the current behavior, this

  5. Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

    PubMed

    Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

    2017-04-01

    An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

  6. Spatial variation in automated burst suppression detection in pharmacologically induced coma.

    PubMed

    An, Jingzhi; Jonnalagadda, Durga; Moura, Valdery; Purdon, Patrick L; Brown, Emery N; Westover, M Brandon

    2015-01-01

    Burst suppression is actively studied as a control signal to guide anesthetic dosing in patients undergoing medically induced coma. The ability to automatically identify periods of EEG suppression and compactly summarize the depth of coma using the burst suppression probability (BSP) is crucial to effective and safe monitoring and control of medical coma. Current literature however does not explicitly account for the potential variation in burst suppression parameters across different scalp locations. In this study we analyzed standard 19-channel EEG recordings from 8 patients with refractory status epilepticus who underwent pharmacologically induced burst suppression as medical treatment for refractory seizures. We found that although burst suppression is generally considered a global phenomenon, BSP obtained using a previously validated algorithm varies systematically across different channels. A global representation of information from individual channels is proposed that takes into account the burst suppression characteristics recorded at multiple electrodes. BSP computed from this representative burst suppression pattern may be more resilient to noise and a better representation of the brain state of patients. Multichannel data integration may enhance the reliability of estimates of the depth of medical coma.

  7. Harnessing Regulatory T cells to Suppress Asthma

    PubMed Central

    Thorburn, Alison N.; Hansbro, Philip M.

    2010-01-01

    Regulatory T cells (Tregs) play an essential role in maintaining the homeostatic balance of immune responses. Asthma is an inflammatory condition of the airways that is driven by dysregulated immune responses toward normally innocuous antigens. Individuals with asthma have fewer and less functional Tregs, which may lead to uncontrolled effector cell responses and promote proasthmatic responses of T helper type 2, T helper 17, natural killer T, antigen-presenting, and B cells. Tregs have the capacity to either directly or indirectly suppress these responses. Hence, the induced expansion of functional Tregs in predisposed or individuals with asthma is a potential approach for the prevention and treatment of asthma. Infection by a number of micro-organisms has been associated with reduced prevalence of asthma, and many infectious agents have been shown to induce Tregs and reduce allergic airways disease in mouse models. The translation of the regulatory and therapeutic properties of infectious agents for use in asthma requires the identification of key modulatory components and the development and trial of effective immunoregulatory therapies. Further translational and clinical research is required for the induction of Tregs to be harnessed as a therapeutic strategy for asthma. PMID:20097830

  8. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    SciTech Connect

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

  9. New approaches to hard bubble suppression

    NASA Technical Reports Server (NTRS)

    Henry, R. D.; Besser, P. J.; Warren, R. G.; Whitcomb, E. C.

    1973-01-01

    Description of a new double-layer method for the suppression of hard bubbles that is more versatile than previously reported suppression techniques. It is shown that it may be possible to prevent hard bubble generation without recourse to exchange coupling of multilayer films.

  10. Suppressive soils: back on the radar screen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Suppressive soils are those in which a pathogen does not establish or persist, establishes but causes little or no damage, or establishes and causes disease for a while but thereafter the disease is less important, although the pathogen may persist in the soil (Weller, 2002). ‘General suppression,’ ...

  11. Ferromagnetic resonance probe liftoff suppression apparatus

    DOEpatents

    Davis, Thomas J.; Tomeraasen, Paul L.

    1985-01-01

    A liftoff suppression apparatus utilizing a liftoff sensing coil to sense the amount a ferromagnetic resonance probe lifts off the test surface during flaw detection and utilizing the liftoff signal to modulate the probe's field modulating coil to suppress the liftoff effects.

  12. Polypyrrole actuators for tremor suppression

    NASA Astrophysics Data System (ADS)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse; West, Keld

    2003-07-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers exemplify "soft actuator" technology that may be especially suitable for use in conjunction with human limbs. The electrochemical and mechanical properties of polypyrrole dodecyl benzene sulphonate actuator films have been studied with this application in mind. The results show that the time constants for the change of length and for the stiffness change are significantly different; the stiffness change being about 10 times faster. Both force measurements and Electrochemical Quartz Crystal Microbalance measurements indicate that the actuation process is complex and involves at least two different processes. The EQCM results make it possible to formulate a hypothesis for the two different time constants: Sodium ions enter the polymer correlated with a fast mass change that probably involves a few (~4) strongly bound water molecules as well. On further reduction, about 10 additional water molecules enter the polymer in a slower process driven by osmotic pressure. Earlier work has tended to focus on achieving the maximum length change, therefore taking the time needed to include all processes. However, since the slower process described above is associated with the lowest strength of the actuator, concentrating on the faster stiffness change results in only a small reduction in the work done by the actuator. This may make actuation at higher frequencies feasible.

  13. Multicopy Suppression Underpins Metabolic Evolvability

    PubMed Central

    Patrick, Wayne M.; Quandt, Erik M.; Swartzlander, Dan B.; Matsumura, Ichiro

    2009-01-01

    Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability. PMID:17884825

  14. Transport suppression by shear reduction

    NASA Astrophysics Data System (ADS)

    Martinell, Julio; Del-Castillo-Negrete, Diego

    2009-11-01

    The relationship between transport and shear is a problem of considerable interest to magnetically confined plasmas. It is well known that there are cases in which an increase of flow shear can lead to a reduction of turbulent transport. However, this is not a generic result, and there are transport problems in which the opposite is the case. In particular, as originally discussed in Ref. footnotetextdel-Castillo-Negrete and Morrison, Phys. Fluids A 5, 948 (1993), barriers to chaotic transport typically form in regions of vanishing shear. This property, which is generic to the so-called non-twist Hamiltonian systems footnotetextdel-Castillo-Negrete, Greene, and Morrison, Physica D 91, 1 (1996), explains the observed resilience of transport barriers in non-monotonic zonal flows in plasmas and fluids and the robustness of shearless magnetic surfaces in reverse shear configurations. Here we study the role of finite Larmor radius (FLR) effects on the suppression of chaotic transport by shear reduction in a simplified model. Following Ref. footnotetextdel-Castillo-Negrete, Phys. Plasmas, 7, 1702 (2000) we consider a model consisting of a superposition of drift waves and a non-monotonic zonal flow. The FLR effects are incorporated by gyroaveraging the E xB velocity, and transport is studied by following the evolution of ensembles of test particles.

  15. TGF-β Suppresses Ift88 Expression in Chondrocytic ATDC5 Cells.

    PubMed

    Kawasaki, Makiri; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Izu, Yayoi; Noda, Masaki

    2015-11-01

    Ift88 is an intraflagella transport protein, critical for the cilium, and has been shown to be required for the maintenance of chondrocytes and cartilage. However, how Ift88 is controlled by cytokines that play a role in osteoarthritis is not well understood. Therefore, we examined the effects of TGF-β on the expression of Ift88. We used ATDC5 cells as chondrocytes and analyzed the effects of TGF-β on gene expression. TGF-β treatment suppresses the levels of Ift88 mRNA in a dose-dependent manner starting from as low as 0.5 ng/mL and reaching the nadir at around 2 ng/mL. TGF-β treatment also suppresses the protein levels of Ift88. TGF-β suppression of Ift88 is still observed when the cells are cultured in the presence of a transcriptional inhibitor while the TGF-β suppression is weakened in the presence of a protein synthesis inhibitor, cycloheximide. TGF-β treatment suppresses the levels of Ift88 mRNA stability suggesting the presence of posttranscriptional regulation. TGF-β treatment reduces the number of cilia positive cells and suppresses average length of cilia. Knockdown of Ift88 by siRNA enhances TGF-β-induced increase in type II collagen mRNA expression in ATDC5 cells revealing the suppressive role of Ift88 on TGF-β-induced regulation of extracellular matrix protein expression. TGF-β also suppresses Ift88 mRNA expression in primary culture of rib chondrocytes. These data indicate that TGF-β regulates Ift88 gene expression at least in part via posttrascriptional manner.

  16. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    SciTech Connect

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

    2014-01-03

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

  17. An Effective Secondary Electron Emission Suppression Treatment For Copper MDC

    NASA Technical Reports Server (NTRS)

    Curren, Arthur N.; Long, Kenwyn J.; Jensen, Kenneth A.; Roman, Robert F.

    1993-01-01

    Untreated oxygen-free, high-conductivity (OFHC) copper, commonly used for MDC electrodes, exhibits relatively high secondary electron emission characteristics. This paper describes a specialized ion-bombardment procedure for texturing copper surfaces which sharply reduces the emission properties relative to untreated copper. The resulting surface is a particle-free, robust, uniformly highly-textured all-metal structure. The use of this process requires no modifications to copper machining, brazing, or other MDC normal fabrication procedures. The flight TWT for a planned NASA deep space probe, the Cassini Mission, will incorporate copper MDC electrodes treated with the method described here.

  18. Impacts of suppressing guide on information spreading

    NASA Astrophysics Data System (ADS)

    Xu, Jinghong; Zhang, Lin; Ma, Baojun; Wu, Ye

    2016-02-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  19. Quercetin suppresses lung cancer growth by targeting Aurora B kinase.

    PubMed

    Xingyu, Zhu; Peijie, Ma; Dan, Peng; Youg, Wang; Daojun, Wang; Xinzheng, Chen; Xijun, Zhang; Yangrong, Song

    2016-11-01

    aurora B kinase is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug to treat tumors. Quercetin was identified to be an antitumor agent. Herein, we report for the first time that quercetin inhibited aurora B activities by directly binding with aurora B in vitro and in vivo. Ex vivo studies showed that quercetin inhibited aurora B activities in JB6 Cl41 cells and A549 lung cancer cells. Moreover, knockdown of aurora B in A549 cells decreased their sensitivities to quercetin. In vivo study demonstrated that injection of quercetin in A549 tumor-bearing mice effectively suppressed cancer growth. The phosphorylation of histone 3 in tumor tissues was also decreased after quercetin treatment. In short, quercetin can suppress growth of lung cancer cells as an aurora B inhibitor both in vitro and in vivo.

  20. The calpain-suppressing effects of olesoxime in Huntington's disease.

    PubMed

    Weber, Jonasz J; Ortiz Rios, Midea M; Riess, Olaf; Clemens, Laura E; Nguyen, Huu P

    2016-01-01

    Olesoxime, a small molecule drug candidate, has recently attracted attention due to its significant beneficial effects in models of several neurodegenerative disorders including Huntington's disease. Olesoxime's neuroprotective effects have been assumed to be conveyed through a direct, positive influence on mitochondrial function. In a long-term treatment study in BACHD rats, the latest rat model of Huntington's disease, olesoxime revealed a positive influence on mitochondrial function and improved specific behavioral and neuropathological phenotypes. Moreover, a novel target of the compound was discovered, as olesoxime was found to suppress the activation of the calpain proteolytic system, a major contributor to the cleavage of the disease-causing mutant huntingtin protein into toxic fragments, and key player in degenerative processes in general. Results from a second model of Huntington's disease, the Hdh (Q111) knock-in mouse, confirm olesoxime's calpain-suppressing effects and support the therapeutic value of olesoxime for Huntington's disease and other disorders involving calpain overactivation.

  1. Eurycoma longifolia extract-artemisinin combination: parasitemia suppression of Plasmodium yoelii-infected mice.

    PubMed

    Mohd Ridzuan, M A R; Sow, A; Noor Rain, A; Mohd Ilham, A; Zakiah, I

    2007-06-01

    Eurycoma longifolia, locally known as 'Tongkat Ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. The claims have been proven scientifically on isolated compounds from the plant. The present study is to investigate the anti malaria properties of Eurycoma longifolia standardized extract (root) (TA164) alone and in combination with artemisinin in vivo. Combination treatment of the standardized extract (TA164) with artemisinin suppressed P. yoelii infection in the experimental mice. The 4 day suppressive test showed that TA164 suppressed the parasitemia of P. yoelii-infected mice as dose dependent manner (10, 30 and 60 mg/kg BW) by oral and subcutaneous treatment. By oral administration, combination of TA164 at 10, 30 and 60 mg/kg BW each with artemisinin respectively showed a significant increase in the parasitemia suppression to 63, 67 and 80 percent as compared to artemisinin single treatment (31%). Using subcutaneous administration, at 10 mg/kg BW of TA164 in combination with 1.7 mg/kg BW of artemisinin gave a suppression of 80% of infection. This study showed that combination treatment of TA164 with artemisinin gives a promising potential anti malaria candidate using both oral and subcutaneous route, the later being the most potent.

  2. Increasing enemy biodiversity strengthens herbivore suppression on two plant species.

    PubMed

    Straub, Cory S; Snyder, William E

    2008-06-01

    Concern over biodiversity loss, especially at higher trophic levels, has led to a surge in studies investigating how changes in natural enemy diversity affect community and ecosystem functioning. These studies have found that increasing enemy diversity can strengthen, weaken, and not affect prey suppression, demonstrating that multi-enemy effects on prey are context-dependent. Here we ask how one factor, plant species identity, influences multi-enemy effects on prey. We focused on two plant species of agricultural importance, potato (Solanum tuberosum), and collards (Brassica oleracea L.). These species share a common herbivorous pest, the green peach aphid (Myzus persicae), but vary in structural and chemical traits that affect aphid reproductive rates and which may also influence inter-enemy interactions. In a large-scale field experiment, overall prey exploitation varied dramatically among the plant species, with enemies reducing aphid populations by approximately 94% on potatoes and approximately 62% on collards. Increasing enemy diversity similarly strengthened aphid suppression on both plants, however, and there was no evidence that plant species identity significantly altered the relationship between enemy diversity and prey suppression. Microcosm experiments suggested that, on both collards and potatoes, intraspecific competition among natural enemies exceeded interspecific competition. Enemy species showed consistent and significant differences in where they foraged on the plants, and enemies in the low-diversity treatment tended to spend less time foraging than enemies in the high-diversity treatment. These data suggest that increasing enemy diversity may strengthen aphid suppression because interspecific differences in where enemies forage on the plant allow for greater resource partitioning. Further, these functional benefits of diversity appear to be robust to changes in plant species identity.

  3. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    NASA Astrophysics Data System (ADS)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  4. Mutual Suppression: Comment on Paulhus et Al. (2004)

    ERIC Educational Resources Information Center

    Nickerson, Carol

    2008-01-01

    Paulhus, Robins, Trzesniewski, and Tracy ("Multivariate Behavioral Research," 2004, 39, 305-328) suggested that the three types of two-predictor suppression situations--classical suppression, cooperative suppression, and net suppression--can all be considered special cases of mutual suppression, in that the magnitude of each of the two…

  5. Psychopathology and Thought Suppression: A Quantitative Review

    PubMed Central

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  6. Suppression effects in feature-based attention

    PubMed Central

    Wang, Yixue; Miller, James; Liu, Taosheng

    2015-01-01

    Attending to a feature enhances visual processing of that feature, but it is less clear what occurs to unattended features. Single-unit recording studies in middle temporal (MT) have shown that neuronal modulation is a monotonic function of the difference between the attended and neuron's preferred direction. Such a relationship should predict a monotonic suppressive effect in psychophysical performance. However, past research on suppressive effects of feature-based attention has remained inconclusive. We investigated the suppressive effect for motion direction, orientation, and color in three experiments. We asked participants to detect a weak signal among noise and provided a partially valid feature cue to manipulate attention. We measured performance as a function of the offset between the cued and signal feature. We also included neutral trials where no feature cues were presented to provide a baseline measure of performance. Across three experiments, we consistently observed enhancement effects when the target feature and cued feature coincided and suppression effects when the target feature deviated from the cued feature. The exact profile of suppression was different across feature dimensions: Whereas the profile for direction exhibited a “rebound” effect, the profiles for orientation and color were monotonic. These results demonstrate that unattended features are suppressed during feature-based attention, but the exact suppression profile depends on the specific feature. Overall, the results are largely consistent with neurophysiological data and support the feature-similarity gain model of attention. PMID:26067533

  7. β₂ adrenergic receptor activation suppresses bone morphogenetic protein (BMP)-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells.

    PubMed

    Yamada, Takayuki; Ezura, Yoichi; Hayata, Tadayoshi; Moriya, Shuichi; Shirakawa, Jumpei; Notomi, Takuya; Arayal, Smriti; Kawasaki, Makiri; Izu, Yayoi; Harada, Kiyoshi; Noda, Masaki

    2015-06-01

    β adrenergic stimulation suppresses bone formation in vivo while its actions in osteoblastic differentiation are still incompletely understood. We therefore examined the effects of β2 adrenergic stimulation on osteoblast-like MC3T3-E1 cells focusing on BMP-induced alkaline phosphatase expression. Morphologically, isoproterenol treatment suppresses BMP-induced increase in the numbers of alkaline phosphatase-positive small foci in the cultures of MC3T3-E1 cells. Biochemically, isoproterenol treatment suppresses BMP-induced enzymatic activity of alkaline phosphatase in a dose-dependent manner. Isoproterenol suppression of alkaline phosphatase activity is observed even when the cells are treated with high concentrations of BMP. With respect to cell density, isoproterenol treatment tends to suppress BMP-induced increase in alkaline phosphatase expression more in osteoblasts cultured at higher cell density. In terms of treatment protocol, continuous isoproterenol treatment is compared to cyclic treatment. Continuous isoproterenol treatment is more suppressive against BMP-induced increase in alkaline phosphatase expression than cyclic regimen. At molecular level, isoproterenol treatment suppresses BMP-induced enhancement of alkaline phosphatase mRNA expression. Regarding the mode of isoproterenol action, isoproterenol suppresses BMP-induced BRE-luciferase activity. These data indicate that isoproterenol regulates BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells.

  8. Best practice guide for the treatment of nightmare disorder in adults.

    PubMed

    Aurora, R Nisha; Zak, Rochelle S; Auerbach, Sanford H; Casey, Kenneth R; Chowdhuri, Susmita; Karippot, Anoop; Maganti, Rama K; Ramar, Kannan; Kristo, David A; Bista, Sabin R; Lamm, Carin I; Morgenthaler, Timothy I

    2010-08-15

    Prazosin is recommended for treatment of Posttraumatic Stress Disorder (PTSD)-associated nightmares. Level A. Image Rehearsal Therapy (IRT) is recommended for treatment of nightmare disorder. Level A. Systematic Desensitization and Progressive Deep Muscle Relaxation training are suggested for treatment of idiopathic nightmares. Level B. Venlafaxine is not suggested for treatment of PTSD-associated nightmares. Level B. Clonidine may be considered for treatment of PTSD-associated nightmares. Level C. The following medications may be considered for treatment of PTSD-associated nightmares, but the data are low grade and sparse: trazodone, atypical antipsychotic medications, topiramate, low dose cortisol, fluvoxamine, triazolam and nitrazepam, phenelzine, gabapentin, cyproheptadine, and tricyclic antidepressants. Nefazodone is not recommended as first line therapy for nightmare disorder because of the increased risk of hepatotoxicity. Level C. The following behavioral therapies may be considered for treatment of PTSD-associated nightmares based on low-grade evidence: Exposure, Relaxation, and Rescripting Therapy (ERRT); Sleep Dynamic Therapy; Hypnosis; Eye-Movement Desensitization and Reprocessing (EMDR); and the Testimony Method. Level C. The following behavioral therapies may be considered for treatment of nightmare disorder based on low-grade evidence: Lucid Dreaming Therapy and Self-Exposure Therapy. Level C No recommendation is made regarding clonazepam and individual psychotherapy because of sparse data.

  9. [Osteoporosis treatment].

    PubMed

    Uebelhart, B; Rizzoli, R

    2006-01-04

    As for any chronic disease, adherence to osteoporosis treatment is low. Folates and vitamin B12 decrease hip fracture risk in elderly Japanese with stroke. Raloxifene (Evista) decreases the incidence of positive estrogen receptor breast cancer and could prevent cardiovascular events in patients at high risk. Strontium ranelate (Protélos) prevents hip fracture in elderly women. The action of alendronate (Fosamax) on bone mineral density and markers of bone remodelling is of higher amplitude than that of risedronate (Actonel). Once monthly ibandronate (Bonviva) increases bone mineral density in post menopausal women with osteoporosis. Excessive suppression of bone remodelling and osteonecrosis of the yaws could be related to bisphosphonate intake.

  10. Integrin endosomal signalling suppresses anoikis

    PubMed Central

    Alanko, Jonna; Mai, Anja; Jacquemet, Guillaume; Schauer, Kristine; Kaukonen, Riina; Saari, Markku; Goud, Bruno; Ivaska, Johanna

    2016-01-01

    to enhanced signalling of co-trafficked receptor tyrosine kinases10, 11 it has remained unclear whether endocytosed active integrins signal in endosomes. Here, we demonstrate that integrin signalling is not restricted to focal adhesions as previously described and that endocytosis is necessary for full ECM-induced, integrin mediated ERK, AKT and FAK signalling. We find that FAK binds directly to and can become activated on purified endosomes. Moreover, the FERM-domain of FAK is able to bind purified integrin containing endosomes, suggesting the potential for integrin signalling complexes to assemble on endosomes after internalization of active integrins. Importantly, FAK is required for anchorage-independent growth and suppression of anoikis 12. Integrin endosomal signalling correlates with reduced anoikis sensitivity in normal cells and anchorage-independent growth and metastasis in breast cancer cells. PMID:26436690

  11. Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ12,14-Prostaglandin J2 (15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4+CD25−FOXP3+ Cells

    PubMed Central

    Benevides, Luciana; Pinto, Larissa G.; Cunha, Thiago M.

    2016-01-01

    The prostaglandin, 15-deoxy Δ12,14-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4+ Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25− population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25− cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA. PMID:27872515

  12. Suppression of immune response to Listeria monocytogenes: mechanism(s) of immune complex suppression.

    PubMed Central

    Virgin, H W; Wittenberg, G F; Bancroft, G J; Unanue, E R

    1985-01-01

    We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. However, these changes were not found in immune complex-suppressed mice. In contrast, membrane interleukin 1 expression was increased in macrophages from suppressed mice compared with macrophages from normal mice. Macrophages from L. monocytogenes-infected normal and immune complex-suppressed mice expressed cytotoxicity against tumor cells in vitro. We conclude that immune complexes do not inhibit resistance to L. monocytogenes by activation of complement or decreasing macrophage cytotoxic activity. Rather, defects in Ia expression by macrophages from suppressed mice might be one component responsible for immune complex suppression of resistance to L. monocytogenes. PMID:3932204

  13. Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation.

    PubMed

    Lee, Jennifer; Baek, Seungye; Lee, Jaeseon; Lee, Juhyun; Lee, Dong-Gun; Park, Mi-Kyung; Cho, Mi-La; Park, Sung-Hwan; Kwok, Seung-Ki

    2015-05-01

    Digoxin is a cardiac glycoside that is commonly used to treat heart failure. Based on its known anti-inflammatory effect, this study was undertaken to investigate the effect of digoxin on collagen-induced arthritis (CIA) and to delineate the underlying mechanism. Digoxin or vehicle was injected intraperitoneally thrice weekly in mice with CIA, from day 7 or day 35 after immunization to investigate preventive or therapeutic effect, respectively. The incidence and severity of arthritis was evaluated. Digoxin treatment suppressed the incidence of arthritis and joint inflammation in mice with CIA. The expression of IL-17 and other proinflammatory cytokines, including IL-1β, IL-6, TNF-α and IL-21, were markedly reduced in the arthritic joints of digoxin-treated CIA mice. Th17 cells and CD4(+) pSTAT3(+) cells were less frequently observed in the spleen of digoxin-treated CIA mice than controls. The mRNA expression of IL-17 and ROR γt was consistently lower in total splenocytes or draining lymph node cells obtained from digoxin-treated CIA mice. Digoxin also reduced in vitro Th17 differentiation and LPS-stimulated IgG production. The number of osteoclasts in the arthritic joint was lower in digoxin-treated mice, whereas digoxin treatment did not directly suppress in vitro osteoclastogenesis. Our findings suggest that digoxin can regulate Th17 and reciprocally promote Treg cells and suppress joint inflammation and bone erosion in CIA. Digoxin may be a therapeutic option by targeting pathogenic Th17 and immunoglobulin production, for treatment of autoimmune arthritis and other Th17-related diseases.

  14. On-off control of burst high frequency electrical stimulation to suppress 4-AP induced seizures

    NASA Astrophysics Data System (ADS)

    Chiang, Chia-Chu; Lin, Chou-Ching K.; Ju, Ming-Shaung

    2013-06-01

    Objective. The goal of this study was to investigate, using model simulations and animal experiments, the efficiency and the side effects of burst high frequency stimulation combined with on-off control in seizure suppression. Approach. A modified mathematical hippocampal seizure model was created to provide evidence of the eligibility of this approach. In the experimental setup, two recording electrodes were inserted into bilateral septal CA1 of the hippocampus, and a stimulation electrode was placed on the ventral hippocampal commissure of a rat. After seizures had been induced by 4-aminopyridine treatment, on-off control stimulation was used to suppress the seizures at 20 s intervals. The stimulation time, cumulative charge and post-stimulation suppression were used to assess the effects of burst duration. Main results. The results showed that burst stimulation could suppress the seizures during the control period and burst stimulation of a shorter duration could keep the seizure suppressed with less effort. By decreasing the burst duration, the cumulative stimulation time became shorter, the delivered cumulative charge became lower, and the cumulative time of post-stimulation suppression became longer. Significance. The on-off control stimulation not only prolonged the duration of suppression but also avoided the side effects of the conversion of seizure patterns. In particular, decreasing the specified burst duration increased the efficiency of the burst stimulation.

  15. Examining the impact of distraction on tic suppression in children and adolescents with Tourette syndrome.

    PubMed

    Conelea, Christine A; Woods, Douglas W

    2008-11-01

    Tourette syndrome (TS) is characterized by motor and/or vocal tics. Tics are thought to be temporarily suppressible, and it is believed that suppression requires significant attentional resources. The aim of the current study was to examine the impact of an attention-demanding distraction task on tic suppression. A secondary aim was to examine whether performance on that task decreased during concomitant periods of suppression. Nine children with TS, ages 9-15, participated in the study. An alternating treatment design was used to compare three conditions, free-to-tic baseline (BL), reinforced tic suppression (SUP) and reinforced tic suppression plus a distraction task (SUP+DIS). Tic frequencies were significantly higher during BL conditions than both SUP and SUP+DIS conditions, and tic frequencies during SUP and SUP+DIS did not differ. Accuracy on the distraction task decreased during SUP+DIS as compared to BL. Results suggest that contextual distractions may not negatively impact tic frequencies. In addition, accuracy on an attention-demanding task may be impacted if a child is simultaneously suppressing.

  16. RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes

    PubMed Central

    Daffu, Gurdip; Shen, Xiaoping; Senatus, Laura; Thiagarajan, Devi; Abedini, Andisheh; Hurtado del Pozo, Carmen; Rosario, Rosa; Song, Fei; Friedman, Richard A.; Ramasamy, Ravichandran

    2015-01-01

    Diabetes exacerbates cardiovascular disease, at least in part through suppression of macrophage cholesterol efflux and levels of the cholesterol transporters ATP binding cassette transporter A1 (ABCA1) and ABCG1. The receptor for advanced glycation end products (RAGE) is highly expressed in human and murine diabetic atherosclerotic plaques, particularly in macrophages. We tested the hypothesis that RAGE suppresses macrophage cholesterol efflux and probed the mechanisms by which RAGE downregulates ABCA1 and ABCG1. Macrophage cholesterol efflux to apolipoprotein A1 and HDL and reverse cholesterol transport to plasma, liver, and feces were reduced in diabetic macrophages through RAGE. In vitro, RAGE ligands suppressed ABCG1 and ABCA1 promoter luciferase activity and transcription of ABCG1 and ABCA1 through peroxisome proliferator–activated receptor-γ (PPARG)–responsive promoter elements but not through liver X receptor elements. Plasma levels of HDL were reduced in diabetic mice in a RAGE-dependent manner. Laser capture microdissected CD68+ macrophages from atherosclerotic plaques of Ldlr−/− mice devoid of Ager (RAGE) displayed higher levels of Abca1, Abcg1, and Pparg mRNA transcripts versus Ager-expressing Ldlr−/− mice independently of glycemia or plasma levels of total cholesterol and triglycerides. Antagonism of RAGE may fill an important therapeutic gap in the treatment of diabetic macrovascular complications. PMID:26253613

  17. Suppressive effect of microRNA-143 in retinoblastoma

    PubMed Central

    Wang, Li-Lun; Hu, Hai-Feng; Feng, Yan-Qin

    2016-01-01

    AIM To investigate microRNA-143 expression and effect on suppression of retinoblastoma (RB) cells. METHODS The expression of microRNA-143 was investigated and compared in normal human retina tissue samples and in RB cell lines of Y79 and Weri1. The microRNA-143 mimics were transfected into the RB cell lines separately, and its effect on RB cell lines was detected using reverse-transcription quantitative polymerase chain reaction and Western blotting methods. RESULTS The microRNA-143 expression was significantly suppressed in RB cell lines. Overexpression of microRNA-143 significantly lowered cell viability and invasion of the RB cell lines, and increased the number of apoptotic cells. Meanwhile, the Bax expression was up-regulated and much higher in the microRNA-143 mimics transfected group than that in the negative control and the microRNA-143 inhibitor groups. CONCLUSION MicroRNA-143 exhibits suppressive effects in RB. The current study provides the perspective of a potential therapeutic treatment for RB. PMID:27990360

  18. Suppression factors in diffractive photoproduction of dijets

    NASA Astrophysics Data System (ADS)

    Klasen, Michael; Kramer, Gustav

    2010-11-01

    Now that new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut.

  19. METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

    DOEpatents

    Visek, W.J.

    1963-04-23

    This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

  20. Suppression as a stereotype control strategy.

    PubMed

    Monteith, M J; Sherman, J W; Devine, P G

    1998-01-01

    Recent research reveals that efforts to suppress stereotypic thoughts can backfire and produce a rebound effect, such that stereotypic thinking increases to a level that is even greater than if no attempt at stereotype control was initially exercised (e.g., Macrae, Bodenhausen, Milne, & Jetten, 1994). The primary goal of this article is to present an in-depth theoretical analysis of stereotype suppression that identifies numerous potential moderators of the effect of stereotype suppression on the likelihood of subsequent rebound. Our analysis of stereotype suppression focuses on two broad issues: the influence of level of prejudice and the influence of processing goals on the activation versus application of stereotypes. Although stereotype rebound occurs under some circumstances, we suggest that a complete understanding of this phenomenon requires consideration of the full array of possible moderating influences.

  1. Puberty suppression in gender identity disorder: the Amsterdam experience.

    PubMed

    Kreukels, Baudewijntje P C; Cohen-Kettenis, Peggy T

    2011-05-17

    The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment steps, and to obtain improved results in the physical appearance of those who opt to continue with sex reassignment. The effects of GnRHa are reversible. However, concerns have been raised about the risk of making the wrong treatment decisions, as gender identity could fluctuate during adolescence, adolescents in general might have poor decision-making abilities, and there are potential adverse effects on health and on psychological and psychosexual functioning. Proponents of puberty suppression emphasize the beneficial effects of GnRHa on the adolescents' mental health, quality of life and of having a physical appearance that makes it possible for the patients to live unobtrusively in their desired gender role. In this Review, we discuss the evidence pertaining to the debate on the effects of GnRHa treatment. From the studies that have been published thus far, it seems that the benefits outweigh the risks. However, more systematic research in this area is needed to determine the safety of this approach.

  2. Inhibition of autophagy may suppress the development of hepatoblastoma.

    PubMed

    Chang, Yanxin; Chen, Lei; Liu, Yuan; Hu, Liang; Li, Liang; Tu, Qianqian; Wang, Ruoyu; Wu, Mengchao; Yang, Jiahe; Wang, Hongyang

    2011-12-01

    Hepatoblastoma (HB) is a rare cancer but represents the most common liver malignancy in children under 3 years of age. Nevertheless, a clear understanding of the pathogenesis is lacking. Although the treatment of HB has been dramatically improved by combining chemotherapy regimens with surgery, its fatal outcome of fast development and recurrence makes new treatment strategies for HB, based on an improved understanding of the pathogenesis, essential. Autophagy is believed to be important in the progression of cancers. However, the role of autophagy in HB remains to be elucidated. Here, we show that autophagy is activated in HB tissues and cells under the conditions of starvation or chemotherapy, coupled with the over-expression of autophagic-related genes BECN1 and ATG5. Suppression of autophagy with pharmacological agents and small interfering RNAs significantly increased cell apoptosis and retarded proliferation in response to nutrition deprivation and treatment with chemotherapeutics. Our data demonstrate that the BECN1 and ATG5-dependent phosphoinositide 3-kinase (PI3K) signaling pathway is essential for the survival of HB cells and their tolerance to chemotherapy and starvation-induced death, and suggests that modifying such autophagic genes may suppress the development of HB, thus offering a therapeutic potential for patients with HB.

  3. Concrete Dust Suppression System. Innovative Technology Summary Report

    SciTech Connect

    1998-12-01

    The improved technology is a water-based dust suppression system for controlling concrete dust generated by demolition equipment, in this case a demolition ram. This demonstration was performed to assess the effectiveness of this system to (1) minimize the amount of water used to suppress potentially contaminated dust, (2) focus the water spray on the dust-generating source and (3) minimize the dust cloud generated by the demolition activity. The technology successfully reduced the water required by a factor of eight compared to the traditional (baseline) method, controlled the dust generated, and permitted a reduction in the work force. The water spray can be focused at the ram point, but it is affected by wind. Prior to the use of this dust control system, dust generated by the demolition ram was controlled manually by spraying with fire hoses (the baseline technology). The improved technology is 18% less expensive than the baseline technology for the conditions and parameters of this demonstration, however, the automated system can save up to 80% versus the baseline whenever waste water treatment costs are considered. For demolishing one high-walled room and a long slab with a total of 413 m{sup 3} (14,580 ft{sup 3}) of concrete, the savings are $105,000 (waste water treatment included). The improved technology reduced the need for water consumption and treatment by about 88% which results in most of the savings.

  4. Marihuana smoking suppresses luteinizing hormone in women.

    PubMed

    Mendelson, J H; Mello, N K; Ellingboe, J; Skupny, A S; Lex, B W; Griffin, M

    1986-06-01

    Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

  5. Investigation of refracting flows for acoustic suppression

    NASA Technical Reports Server (NTRS)

    Sloan, D.; Purves, R. B.; Farquhar, B. W.

    1977-01-01

    An experimental investigation to determine the possibility of using refracting flows for the suppression of aircraft inlet noise is described. Observations of wave refraction in duct flows and measurements of the increase in effectiveness of acoustic linings due to refraction have suggested methods for the design of engine inlet ducts which can either suppress noise internally or direct it to where it causes less annoyance.

  6. Flame Suppression Agent, System and Uses

    NASA Technical Reports Server (NTRS)

    Parrish, Clyde F. (Inventor)

    2013-01-01

    Aqueous droplets encapsulated in a flame retardant polymer are useful in suppressing combustion. Upon exposure to a flame, the encapsulated aqueous droplets rupture and vaporize, removing heat and displacing oxygen to retard the combustion process. The polymer encapsulant, through decomposition, may further add free radicals to the combustion atmosphere, thereby further retarding the combustion process. The encapsulated aqueous droplets may be used as a replacement to halon, water mist and dry powder flame suppression systems.

  7. Measurement of myeloid cell immune suppressive activity.

    PubMed

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  8. Method for Transducer Transient Suppression. I. Theory

    DTIC Science & Technology

    1992-09-01

    Vol. 92, No. 3, September 1992 Method for transducer transient suppression. I: Theory Jean C. Piquette Naval Research Laboratory. Underwater Sound...TITLE AND SUBTITLE 5. FUNDING NUMBERS Method for transducer transient suppression. I: Theo:y PE - 61153N TA - RROII-08-42 WU - DN220-161 6. AUTHOR(S) Jean...STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution unlimited. 13. ABSTRACT (Maximum 200 words) The problem of driving a transducer in

  9. Kaposi's sarcoma following immune suppressive therapy for Wegener's granulomatosis.

    PubMed

    Deschênes, Isabelle; Dion, Louise; Beauchesne, Claude; de Brum-Fernandes, Artur

    2003-03-01

    The association between Kaposi's sarcoma and infection with human herpesvirus 8 is now well recognized. Immunologic impairment is associated with 2 forms of Kaposi's sarcoma, epidemic [associated with human immunodeficiency virus (HIV) infection] and iatrogenic (associated with immunosuppressive treatment); both forms have become more common during the last decade. We describe an HIV negative 54-year-old man who developed Kaposi's sarcoma 2 months after the beginning of immuno-suppressive therapy for Wegener's granulomatosis (WG). With tapering of medication, complete remission of Kaposi's sarcoma was achieved in one year. To our knowledge, this is the second reported case of iatrogenic Kaposi's sarcoma in a patient with WG.

  10. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  11. Noise suppression in surface microseismic data

    USGS Publications Warehouse

    Forghani-Arani, Farnoush; Batzle, Mike; Behura, Jyoti; Willis, Mark; Haines, Seth S.; Davidson, Michael

    2012-01-01

    We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform. We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform.

  12. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    PubMed

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  13. The temporal frequency tuning of continuous flash suppression reveals peak suppression at very low frequencies

    PubMed Central

    Han, Shui’er; Lunghi, Claudia; Alais, David

    2016-01-01

    Continuous flash suppression (CFS) is a psychophysical technique where a rapidly changing Mondrian pattern viewed by one eye suppresses the target in the other eye for several seconds. Despite the widespread use of CFS to study unconscious visual processes, the temporal tuning of CFS suppression is currently unknown. In the present study we used spatiotemporally filtered dynamic noise as masking stimuli to probe the temporal characteristics of CFS. Surprisingly, we find that suppression in CFS peaks very prominently at approximately 1 Hz, well below the rates typically used in CFS studies (10 Hz or more). As well as a strong bias to low temporal frequencies, CFS suppression is greater for high spatial frequencies and increases with increasing masker contrast, indicating involvement of parvocellular/ventral mechanisms in the suppression process. These results are reminiscent of binocular rivalry, and unifies two phenomenon previously thought to require different explanations. PMID:27767078

  14. Viral re-suppression and detection of drug resistance following interruption of a suppressive NNRTI-based regimen

    PubMed Central

    Fox, Zoe; Phillips, Andrew; Cohen, Cal; Neuhaus, Jacquie; Baxter, John; Emery, Sean; Hirschel, Bernard; Hullsiek, Kathy Huppler; Stephan, Christoph; Lundgren, Jens

    2009-01-01

    Background Interruption of an NNRTI-regimen is often necessary, but must be performed with caution because NNRTIs have a low genetic barrier to resistance. Limited data exist to guide clinical practice on the best interruption strategy to use. Methods Patients in the drug-conservation arm of SMART who interrupted a fully suppressive NNRTI-regimen were evaluated. From 2003, SMART recommended interruption of an NNRTI by: a staggered-interruption, where the NNRTI was stopped before the NRTIs; or by replacing the NNRTI with another drug before interruption. Simultaneous-interruption of all ARVs was discouraged. Re-suppression rates four-to-eight months after re-initiating NNRTI-therapy were assessed, as was the detection of drug-resistance mutations within two months of the treatment interruption in a subset (N=141). Results Overall, 601/688 (87.4%) patients who re-started an NNRTI achieved viral re-suppression. The adjusted odds ratio (95% CI) for achieving re-suppression was 1.94 (1.02-3.69) for patients with a staggered-interruption and 3.64 (1.37-9.64) for those with a switched-interruption compared to patients with a simultaneous-interruption. At least one NNRTI-mutation was detected in the virus of 16.4% patients with simultaneous-interruption, 12.5% patients with staggered-interruption and 4.2% patients with switched-interruption. Fewer patients with detectable mutations (i.e. 69.2%) achieved HIV-RNA≤400 copies/mL compared to those in whom no mutations were detected (i.e. 86.7%), p=0.05. Conclusions In patients who interrupt a suppressive NNRTI-regimen, the choice of interruption-strategy may influence re-suppression rates when re-starting a similar regimen. NNRTI drug-resistance mutations were observed in a relatively high proportion of patients. These data provide additional support for a staggered- or switched-interruption strategy for NNRTI drugs. PMID:18981767

  15. Mechanical suppression of essential tremor.

    PubMed

    Rocon, Eduardo; Manto, Mario; Pons, Jose; Camut, Stephane; Belda, Juan Manuel

    2007-01-01

    This paper describes a new treatment for essential tremor. A wearable orthosis, which can be adapted to each configuration of each joint of the upper limb, is able to apply effective dynamic force between consecutive segments of the upper limb and change its biomechanical characteristics. The orthosis is controlled by a computer with a dedicated software application that distinguishes between real time tremor and voluntary movement. The wearable orthosis is able to detect position, rate and acceleration of rotation of the joint by means of a chip gyroscope. This technology was evaluated in six patients suffering from essential tremor. The technique is non invasive and represents an alternative to medication and deep brain stimulation.

  16. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

    PubMed

    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  17. Feature-based attention modulates surround suppression

    PubMed Central

    Flevaris, Anastasia V.; Murray, Scott O.

    2015-01-01

    Stimuli appearing in the surround of the classical receptive field (CRF) can reduce neuronal firing and perceived contrast of a preferred stimulus in the CRF, a phenomenon referred to as surround suppression. Suppression is greatest when the surrounding stimulus has the same orientation and spatial frequency (SF) as the central target. Although spatial attention has been shown to influence surround suppression, the effects of feature-based attention have yet to be characterized. Using behavioral contrast adaptation in humans, we examined center-surround interactions between SF and orientation, and asked whether attending to one feature dimension versus the other influenced suppression. A center-surround triplet comprised of a central target Gabor and two flanking Gabors were used for adaptation. The flankers could have the same SF and orientation as the target, or differ in one or both of the feature dimensions. Contrast thresholds were measured for the target before and after adapting to center-surround triplets, and postadaptation thresholds were taken as an indirect measure of surround suppression. Both feature dimensions contributed to surround suppression and did not summate. Moreover, when center and surround had the same feature value in one dimension (e.g., same orientation) but had different values in the other dimension (e.g., different SF), there was more suppression when attention was directed to the feature dimension that matched between center and surround than when attention was directed to the feature dimension that differed. These results demonstrate that feature-based attention can influence center-surround interactions by enhancing the effects of the attended dimension. PMID:25630380

  18. Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

    PubMed Central

    Zhao, Jing; Ha, Yonju; Liou, Gregory I.; Gonsalvez, Graydon B.; Smith, Sylvia B.; Bollinger, Kathryn E.

    2014-01-01

    Purpose. To evaluate the effects of the σ 1 receptor (σR1) agonist, (+)-pentazocine, on lipopolysaccharide (LPS)–induced inflammatory changes in retinal microglia cells. Methods. Retinal microglia cells were isolated from Sprague-Dawley rat pups. Cells were treated with LPS with or without (+)-pentazocine and with or without the σR1 antagonist BD1063. Morphologic changes were assayed. Cell viability was assessed by using MTT assay. Supernatant levels of tumor necrosis factor α (TNF-α), interleukin 10, (IL-10), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO) were determined. Reactive oxygen species (ROS) formation was assayed, and levels of mitogen-activated protein kinases (MAPKs) were analyzed by using Western blot. Results. The σR1 protein was expressed in retinal microglia. Incubation with LPS and/or (+)-pentazocine did not alter cell viability or σR1 protein levels. Incubation with LPS for 24 hours induced a marked change in microglial morphology and a significant increase in secreted levels of TNF-α, IL-10, MCP-1, and NO. Pretreatment with (+)-pentazocine inhibited the LPS-induced morphologic changes. Release of TNF-α, IL-10, MCP-1, and NO was reduced with (+)-pentazocine. Intracellular ROS formation was suppressed with (+)-pentazocine. Phosphorylation of extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was reduced in the presence of (+)-pentazocine. The σR1 antagonist BD1063 blocked the (+)-pentazocine–mediated inhibition of LPS-induced morphologic changes. In addition, BD1063 treatment blocked (+)-pentazocine–mediated suppression of LPS-induced TNF-α, IL-10, MCP-1, NO, and intracellular ROS release. Conclusions. Treatment with (+)-pentazocine suppressed inflammatory responses of retinal microglia and inhibited LPS-induced activation of ERK/JNK MAPK. In neurodegenerative disease, (+)-pentazocine may exert neuroprotective effects through manipulation of microglia. PMID:24812552

  19. Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase.

    PubMed

    Yano, Akiko; Kubota, Masafumi; Iguchi, Kazuhiro; Usui, Shigeyuki; Hirano, Kazuyuki

    2006-05-01

    The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.

  20. The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder

    PubMed Central

    Arnsten, Amy F.T.; Raskind, Murray A.; Taylor, Fletcher B.; Connor, Daniel F.

    2014-01-01

    Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE) system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors), which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders. PMID:25436222

  1. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    SciTech Connect

    Tsai, Cheng Ying; Douglas, David R.; Li, Rui; Tennant, Christopher D.; di Mitri, Simone

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  2. Suppression of branches in Eucalyptus trees.

    PubMed

    Senthalir, P; Sharanya, S; Paramathma, M

    2004-06-01

    The effect of neem oil, which acts as a suckericide in tobacco, on branch suppression in Eucalyptus tereticornis was assessed to help maximize stem biomass. Lateral branches of selected trees were pruned, and neem oil solutions at concentrations of either 80%, 40%, 20%, 10%, or 0% (untreated control) were applied to leaf axils of the pruned branches. Regeneration of branches was suppressed, and the magnitude of suppression was proportional to the concentration of neem oil. Compared to the control, the percentage reduction in branching at 80% neem oil was 41.6%. When regenerated branches were repruned and neem oil applied at either 100%, 80%, or 0% (control), the regenerating ability of these branches was severely repressed by 78% at 100% neem oil relative to the control. Apical shoots were also topped and treated at either 100% or 0% (control) neem oil to identify the principal suppressive component in neem oil. The principal component azadirachtin was tested at 375, 750, 1500, 3125, 6250, 12 500, 25 000, 50 000, and 100 000 ppm and 0 ppm as the control. Reduction in the coppicing shoot was as high as 85%. Azadirachtin was responsible for the suppression. By pruning the lateral branches with neem oil, wasteful consumption of photosynthates can be precluded and the stem biomass maximized.

  3. Rutin suppresses atopic dermatitis and allergic contact dermatitis.

    PubMed

    Choi, Jin Kyeong; Kim, Sang-Hyun

    2013-04-01

    Atopic dermatitis (AD) and allergic contact dermatitis (ACD) is a common allergic inflammatory skin disease caused by a combination of eczematous, scratching, pruritus and cutaneous sensitization with allergens. The aim of our study was to examine whether rutin, a predominant flavonoid having anti-inflammatory and antioxidative potential, modulates AD and ACD symptoms. We established an atopic dermatitis model in BALB/c mice by repeated local exposure of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, 2,4-dinitroflourobenzene-sensitized a local lymph node assay was used for the ACD model. Repeated alternative treatment of DFE/DNCB caused AD symptoms. Topical application of rutin reduced AD based on ear thickness and histopathological analysis, in addition to serum IgE levels. Rutin inhibited mast cell infiltration into the ear and serum histamine level. Rutin suppressed DFE/DNCB-induced expression of interleukin (IL)-4, IL-5, IL-13, IL-31, IL-32 and interferon (INF)-γ in the tissue. In addition, rutin suppressed ACD based on ear thickness and lymphocyte proliferation, serum IgG2a levels, and expression of INF-γ, IL-4, IL-5, IL-10, IL-17 and tumour necrosis factor-α in ACD ears. This study demonstrates that rutin inhibits AD and ACD, suggesting that rutin might be a candidate for the treatment of allergic skin diseases.

  4. Stromal heparan sulfate differentiates neuroblasts to suppress neuroblastoma growth.

    PubMed

    Knelson, Erik H; Gaviglio, Angela L; Nee, Jasmine C; Starr, Mark D; Nixon, Andrew B; Marcus, Stephen G; Blobe, Gerard C

    2014-07-01

    Neuroblastoma prognosis is dependent on both the differentiation state and stromal content of the tumor. Neuroblastoma tumor stroma is thought to suppress neuroblast growth via release of soluble differentiating factors. Here, we identified critical growth-limiting components of the differentiating stroma secretome and designed a potential therapeutic strategy based on their central mechanism of action. We demonstrated that expression of heparan sulfate proteoglycans (HSPGs), including TβRIII, GPC1, GPC3, SDC3, and SDC4, is low in neuroblasts and high in the Schwannian stroma. Evaluation of neuroblastoma patient microarray data revealed an association between TGFBR3, GPC1, and SDC3 expression and improved prognosis. Treatment of neuroblastoma cell lines with soluble HSPGs promoted neuroblast differentiation via FGFR1 and ERK phosphorylation, leading to upregulation of the transcription factor inhibitor of DNA binding 1 (ID1). HSPGs also enhanced FGF2-dependent differentiation, and the anticoagulant heparin had a similar effect, leading to decreased neuroblast proliferation. Dissection of individual sulfation sites identified 2-O, 3-O-desulfated heparin (ODSH) as a differentiating agent, and treatment of orthotopic xenograft models with ODSH suppressed tumor growth and metastasis without anticoagulation. These studies support heparan sulfate signaling intermediates as prognostic and therapeutic neuroblastoma biomarkers and demonstrate that tumor stroma biology can inform the design of targeted molecular therapeutics.

  5. Suppression of benign prostate hyperplasia by Kaempferia parviflora rhizome

    PubMed Central

    Murata, Kazuya; Hayashi, Hirotaka; Matsumura, Shinichi; Matsuda, Hideaki

    2013-01-01

    Background: Kaempferia parviflora rhizome is used as a folk medicine in Thailand for the treatment of various symptoms. In the present study, the inhibitory activities of extract from K. parviflora rhizome against 5α-reductase (5αR) were subjected. Furthermore, the effects of the extract from K. parviflorar hizome in benign prostate hyperplasia (BPH) were studied using the model mice. Materials and Methods: Preparations of extracts from the rhizomes of K. parviflora, Curcuma zedoaria and Zingiber officinale, and methoxyflavones isolated from K. parviflora was used for 5αR inhibition assay. The effects of K. parviflora extract on growth suppression for the prostates and seminal vesicles were performed based on the Hershberger's method. The K. parviflora extract was administered to castrated mice for 14 days. Results: K. parviflora extract showed more potent inhibitory activity on 5αR than C. zedoaria and Z. officinale extracts. The active principles were identified as 3,5,7,3’,4’-pentamethoxyflavone and 5,7,3’,4’-tetramethoxyflavone by activity guided fractionation. Furthermore, K. parviflora extract suppressed the weights of prostates and seminal vesicles in BPH model rats by daily administration for 14 days. Conclusion: These results indicate that K. parviflora extract can be a promising agent for the treatment of BPH. PMID:24174827

  6. Pyrroloquinoline-Quinone Suppresses Liver Fibrogenesis in Mice

    PubMed Central

    Jia, Dongwei; Duan, Fangfang; Peng, Peike; Sun, Linlin; Ruan, Yuanyuan; Gu, Jianxin

    2015-01-01

    Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injuries, and its progression toward cirrhosis is the major cause of liver-related morbidity and mortality worldwide. However, anti-fibrotic treatment remains an unconquered area for drug development. Accumulating evidence indicate that oxidative stress plays a critical role in liver fibrogenesis. In this study, we found that PQQ, a natural anti-oxidant present in a wide variety of human foods, exerted potent anti-fibrotic and ROS-scavenging activity in Balb/C mouse models of liver fibrosis. The antioxidant activity of PQQ was involved in the modulation of multiple steps during liver fibrogenesis, including chronic liver injury, hepatic inflammation, as well as activation of hepatic stellate cells and production of extracellular matrix. PQQ also suppressed the up-regulation of RACK1 in activated HSCs in vivo and in vitro. Our data suggest that PQQ suppresses oxidative stress and liver fibrogenesis in mice, and provide rationale for the clinical application of PQQ in the prevention and treatment of liver fibrosis. PMID:25822822

  7. Salvia plebeia suppresses atopic dermatitis-like skin lesions.

    PubMed

    Choi, Jin Kyeong; Oh, Hyun-Mee; Lee, Soyoung; Kwon, Taeg Kyu; Shin, Tae-Yong; Rho, Mun-Chual; Kim, Sang-Hyun

    2014-01-01

    Salvia plebeia R. Br. (Lamiaceae) has been used for folk medicines in Asian countries, including Korea and China, to treat skin inflammatory diseases and asthma. In this study, we investigated the effects of S. plebeia extract (SPE) on atopic dermatitis (AD)-like skin lesions and defined underlying mechanisms of action. We established an AD model in BALB/c mice by repeated local exposure of house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like skin lesions. The oral administration of SPE decreased AD symptoms based on ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. SPE suppressed mast cell infiltration into the ear and serum histamine level. SPE inhibited Th1/Th2/Th17 phenotype CD4(+) T lymphocytes expansion in the lymph node and the expression of Th1/Th2/Th17 cytokines in the ear tissue. To define the underlying mechanisms of action, the tumor necrosis factor (TNF)-α and interferon (IFN)-γ activated human keratinocytes (HaCaT) model was used. SPE significantly suppressed the expression of cytokines and chemokines through the down-regulation of mitogen-activated protein kinases, nuclear factor-κB, and STAT1 in HaCaT cells. Taken together, our results suggest that SPE might be a candidate for the treatment of AD.

  8. Modulation of radiation-induced hemopoietic suppression by acute thrombocytopenia

    SciTech Connect

    Ebbe, S.; Phalen, E.; Threatte, G.; Londe, H.

    1985-01-01

    Modifications of radiation-induced hemopoietic suppression by acute thrombocytopenia were evaluated. Immediately before or after exposure to sublethal irradiation, mice were given a single injection of anti-mouse platelet serum (APS), normal heterologous serum, neuraminidase (N'ase), or saline, or no further treatment was provided. Hemopoiesis was evaluated by blood cell counts, hematocrits, and incorporation of (75Se)selenomethionine into platelets. APS and N'ase induced an acute thrombocytopenia from which there was partial recovery before the platelet count started to fall from the radiation. During the second post-treatment week, both thrombocytopoiesis and erythropoiesis were greater in mice that received APS or N'ase in addition to radiation than in control irradiated mice. Differences in leukopoiesis were not apparent. Therefore, both thrombocytopoiesis and erythropoiesis appeared to be responsive to a stimulus generated by acute thrombocytopenia in sublethally irradiated mice.

  9. Estrogen suppresses adipogenesis by inhibiting S100A16 expression

    PubMed Central

    Zhang, Rihua; Su, Dongming; Zhu, Weidong; Huang, Qiong; Liu, Menglan; Xue, Yi; Zhang, Yuanyuan; li, Dong; Zhao, Allan; Liu, Yun

    2014-01-01

    The aim of this study is to determine the effects of E2 on metabolic syndrome and the molecular mechanisms involving S100A16. Ovariectomized (OVX) rat models and mouse embryonic fibroblasts cell models were used. E2 loss in OVX rats induced body weight gain and central abdominal fat accumulation, which were ameliorated by E2 treatment under chow and high-fat diet (HFD) conditions. E2 decreased the expression of the adipocyte marker genes PPAR γ, aP2, C/EBP α, and S100A16. E2 inhibited adipogenesis. Overexpression of S100A16 reversed the E2-induced adipogenesis effect. A luciferase assay showed that E2 inhibited the expression of S100A16. E2 treatment decreased body weight gain and central abdominal fat accumulation under both chow and HFD conditions. Also, E2 suppressed adipogenesis by inhibiting S100A16 expression. PMID:24501224

  10. Tactical Checkpoint: Hail/Warn Suppress/Stop (Poster)

    DTIC Science & Technology

    2010-11-15

    distractor , optical suppression , human behavior, checkpoint, ambient light, driver suppression , human experimentation, light, paintball, obscuration...HAIL/WARN AND - SUPPRESS /STOP Poster Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER...warning to a driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression

  11. Suppressive Activity of Quercetin on Periostin Functions In Vitro.

    PubMed

    Irie, Shinji; Kashiwabara, Misako; Yamada, Asako; Asano, Kazuhito

    2016-01-01

    Periostin, a 90-kDa extracellular matrix protein, has been attracting attention as a novel biomarker of airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although oral administration of quercetin to patients with AR can favorably modify the clinical condition of this disease, the influence of quercetin on periostin functions is not well understood. The present study was, therefore, undertaken to examine the influence of quercetin on the production of both periostin and periostin-induced eosinophil chemoattractants from human nasal epithelial cells (HNEpC) in vitro. HNEpC were stimulated with 15.0 ng/ml interleukin (IL)-4 in the absence or presence of quercetin for 72 h. Periostin levels in the culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Addition of 4.0 μM quercetin into cell cultures suppressed periostin production from HNEpC that was induced by IL-4 stimulation through inhibitation of signal transducer and activator of transcription 6 (STAT6) activation. We then examined whether quercetin could inhibit production of the periostin-induced eosinophil chemoattractants, regulated on activation, normal T-cell expressed and secreted (RANTES) and eotaxin, from HNEpC. HNEpC were stimulated with 2.0 ng/ml periostin in the absence or presence of quercetin for 72 h. RANTES and eotaxin levels in culture supernatants were examined using ELISA. Treatment of HNEpC with quercetin at a concentration of 4.0 μM suppressed the ability of cells to produce RANTES and eotaxin. This suppression was mediated through suppression of activation of the transcription factor nuclear factor-kappa B (NF-κB) p65, as measured using ELISA, and of chemokine mRNA expression, as measured using reverse transcriptase-polymerase chain reaction (RT-PCR). These results strongly suggest that quercetin suppresses the production of both periostin and periostin-induced eosinophil chemoattractants from HNEpC and results in improvement of the

  12. Appetite suppressants and valvular heart disease.

    PubMed

    Weissman, N J

    2001-04-01

    The association between valvular heart disease and diet pills was discovered several years ago in a small cohort of patients. Subsequent uncontrolled surveys and reports suggested a prevalence of cardiac abnormalities as high as 30%. These results led to widespread concern by millions of appetite suppressant users and the withdrawal of both fenfluramine and dexfenfluramine from the market. Through this review of the literature, it becomes apparent that we have better defined the association between valvular heart disease and appetite suppressants; nonetheless, many questions and controversies remain. Most large scale, multicenter, controlled studies have shown that a prevalence of significant valve regurgitation is between 2 and 12% and that the likelihood of disease increases with increasing dose and/or duration of appetite suppressant use, but several other issues, such as the mechanism of action, remain unanswered.

  13. Wing rock suppression using forebody vortex control

    NASA Technical Reports Server (NTRS)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  14. Implicitly learned suppression of irrelevant spatial locations.

    PubMed

    Leber, Andrew B; Gwinn, Rachael E; Hong, Yoolim; O'Toole, Ryan J

    2016-12-01

    How do we ignore a salient, irrelevant stimulus whose location is predictable? A variety of studies using instructional manipulations have shown that participants possess the capacity to exert location-based suppression. However, for the visual search challenges we face in daily life, we are not often provided explicit instructions and are unlikely to consciously deliberate on what our best strategy might be. Instead, we might rely on our past experience-in the form of implicit learning-to exert strategic control. In this paper, we tested whether implicit learning could drive spatial suppression. In Experiment 1, participants searched displays in which one location contained a target, while another contained a salient distractor. An arrow cue pointed to the target location with 70 % validity. Also, unbeknownst to the participants, the same arrow cue predicted the distractor location with 70 % validity. Results showed facilitated RTs to the predicted target location, confirming target enhancement. Critically, distractor interference was reduced at the predicted distractor location, revealing that participants used spatial suppression. Further, we found that participants had no explicit knowledge of the cue-distractor contingencies, confirming that the learning was implicit. In Experiment 2, to seek further evidence for suppression, we modified the task to include occasional masked probes following the arrow cue; we found worse probe identification accuracy at the predicted distractor location than control locations, providing converging evidence that observers spatially suppressed the predicted distractor locations. These results reveal an ecologically desirable mechanism of suppression, which functions without the need for conscious knowledge or externally guided instructions.

  15. Large-Scale Identification and Analysis of Suppressive Drug Interactions

    PubMed Central

    Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P.

    2014-01-01

    SUMMARY One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

  16. Vibration Isolation, Suppression, Steering, and Pointing (VISSP)

    NASA Technical Reports Server (NTRS)

    Wada, Ben K.; Rahman, Zahidul; Kedikian, Roland

    1996-01-01

    The design of a six degree of freedom flight vibration isolation suppression and steering (VISS) subsystem for a mid-wave infrared camera on the top of a spacecraft is presented. The development of a long stroke piezoelectric, redundant, compact, low stiffness and power efficient actuator is summarized. A subsystem that could be built and validated for flight within 15 months was investigated. The goals of the VISS are 20 dB vibration isolation above 2 Hz, 15 dB vibration suppression of disturbances at about 60 Hz and 120 Hz, and +/- 0.3 deg steering at 2 Hz and 4 Hz.

  17. Active Suppression Of Vibrations On Aircraft Structures

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    1995-01-01

    Method of active suppression of nonlinear and nonstationary vibrations developed to reduce sonic fatigue and interior noise in high-speed aircraft. Structure of aircraft exhibits periodic, chaotic, and random vibrations when forced by high-intensity sound from jet engines, shock waves, turbulence, and separated flows. Method of suppressing vibrations involves feedback control: Strain gauges or other sensors mounted in paths of propagation of vibrations on structure sense vibrations; outputs of sensors processed into control signal applied to actuator mounted on structure, inducing compensatory forces.

  18. Immune suppressive mechanisms in the tumor microenvironment.

    PubMed

    Munn, David H; Bronte, Vincenzo

    2016-04-01

    Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of immunotherapy of cancer.

  19. Glucocorticoids Suppress Selected Components of the Senescence-Associated Secretory Phenotype

    PubMed Central

    Laberge, Remi-Martin; Zhou, Lili; Sarantos, Melissa R.; Rodier, Francis; Freund, Adam; de Keizer, Peter L.J.; Liu, Su; Demaria, Marco; Cong, Yu-Sheng; Kapahi, Pankaj; Desprez, Pierre-Yves; Hughes, Robert E.; Campisi, Judith

    2012-01-01

    SUMMARY Cellular senescence suppresses cancer by arresting the proliferation of cells at risk for malignant transformation. Recently, senescent cells were shown to secrete numerous cytokines, growth factors and proteases that can alter the tissue microenvironment and may promote age-related pathology. To identify small molecules that suppress the senescence-associated secretory phenotype (SASP), we developed a screening protocol using normal human fibroblasts and a library of compounds that are approved for human use. Among the promising library constituents was the glucocorticoid corticosterone. Both corticosterone and the related glucocorticoid cortisol decreased the production and secretion of selected SASP components, including several pro-inflammatory cytokines. Importantly, the glucocorticoids suppressed the SASP without reverting the tumor suppressive growth arrest, and were efficacious whether cells were induced to senesce by ionizing radiation or strong mitogenic signals delivered by oncogenic RAS or MAP kinase kinase 6 overexpression. Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1α signaling and NF-κB transactivation activity. Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1α efficiently reestablished NF-κB transcriptional activity and IL-6 secretion. Our findings demonstrate feasibility of screening for compounds that inhibit the effects of senescent cells. They further show that glucocorticoids inhibit selected components of the SASP, and suggest that corticosterone and cortisol, two FDA-approved drugs, might exert their effects in part by suppressing senescence-associated inflammation. PMID:22404905

  20. Glucocorticoids suppress selected components of the senescence-associated secretory phenotype.

    PubMed

    Laberge, Remi-Martin; Zhou, Lili; Sarantos, Melissa R; Rodier, Francis; Freund, Adam; de Keizer, Peter L J; Liu, Su; Demaria, Marco; Cong, Yu-Sheng; Kapahi, Pankaj; Desprez, Pierre-Yves; Hughes, Robert E; Campisi, Judith

    2012-08-01

    Cellular senescence suppresses cancer by arresting the proliferation of cells at risk for malignant transformation. Recently, senescent cells were shown to secrete numerous cytokines, growth factors, and proteases that can alter the tissue microenvironment and may promote age-related pathology. To identify small molecules that suppress the senescence-associated secretory phenotype (SASP), we developed a screening protocol using normal human fibroblasts and a library of compounds that are approved for human use. Among the promising library constituents was the glucocorticoid corticosterone. Both corticosterone and the related glucocorticoid cortisol decreased the production and secretion of selected SASP components, including several pro-inflammatory cytokines. Importantly, the glucocorticoids suppressed the SASP without reverting the tumor suppressive growth arrest and were efficacious whether cells were induced to senesce by ionizing radiation or strong mitogenic signals delivered by oncogenic RAS or MAP kinase kinase 6 overexpression. Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1α signaling and NF-κB transactivation activity. Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1α efficiently reestablished NF-κB transcriptional activity and IL-6 secretion. Our findings demonstrate feasibility of screening for compounds that inhibit the effects of senescent cells. They further show that glucocorticoids inhibit selected components of the SASP and suggest that corticosterone and cortisol, two FDA-approved drugs, might exert their effects in part by suppressing senescence-associated inflammation.

  1. Histidine augments the suppression of hepatic glucose production by central insulin action.

    PubMed

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2013-07-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

  2. The activating transcription factor 3 protein suppresses the oncogenic function of mutant p53 proteins.

    PubMed

    Wei, Saisai; Wang, Hongbo; Lu, Chunwan; Malmut, Sarah; Zhang, Jianqiao; Ren, Shumei; Yu, Guohua; Wang, Wei; Tang, Dale D; Yan, Chunhong

    2014-03-28

    Mutant p53 proteins (mutp53) often acquire oncogenic activities, conferring drug resistance and/or promoting cancer cell migration and invasion. Although it has been well established that such a gain of function is mainly achieved through interaction with transcriptional regulators, thereby modulating cancer-associated gene expression, how the mutp53 function is regulated remains elusive. Here we report that activating transcription factor 3 (ATF3) bound common mutp53 (e.g. R175H and R273H) and, subsequently, suppressed their oncogenic activities. ATF3 repressed mutp53-induced NFKB2 expression and sensitized R175H-expressing cancer cells to cisplatin and etoposide treatments. Moreover, ATF3 appeared to suppress R175H- and R273H-mediated cancer cell migration and invasion as a consequence of preventing the transcription factor p63 from inactivation by mutp53. Accordingly, ATF3 promoted the expression of the metastasis suppressor SHARP1 in mutp53-expressing cells. An ATF3 mutant devoid of the mutp53-binding domain failed to disrupt the mutp53-p63 binding and, thus, lost the activity to suppress mutp53-mediated migration, suggesting that ATF3 binds to mutp53 to suppress its oncogenic function. In line with these results, we found that down-regulation of ATF3 expression correlated with lymph node metastasis in TP53-mutated human lung cancer. We conclude that ATF3 can suppress mutp53 oncogenic function, thereby contributing to tumor suppression in TP53-mutated cancer.

  3. Controlled suppression of the photoluminescence superlinear dependence on excitation density in quantum dots.

    PubMed

    Bietti, Sergio; Sanguinetti, Stefano

    2012-10-04

    : We have shown that it is possible to tune, up to complete suppression, the photoluminescence superlinear dependence on the excitation density in quantum dot samples at high temperatures by annealing treatments. The effect has been attributed to the reduction of the defectivity of the material induced by annealing.

  4. Animal and pasture responses to grazing management of chemically suppressed tall fescue in mixed pastures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Treatment of toxic endophyte-infected tall fescue [Lolium arundinaceum (Schreb.) Darbysh] with metsulfuran-methyl can mitigate fescue toxicosis and enhance forage nutritive value by suppressing seedhead emergence. A grazing experiment was conducted with steers (2013) and heifers (2014) to evaluate a...

  5. Suppressing weed growth after wheat harvest with underseeded red clover in organic farming

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organic producers are seeking alternative tactics for weed control so that they can reduce their need for tillage. In this study, we examined cover crop strategies for suppressing weed growth after harvest of wheat. Two cover crop treatments, red clover (mammoth type) or a mixture of oat and dry p...

  6. Antagonistic effect of polyamines on ABA-induced suppression of mitosis in Allium cepa L.

    PubMed

    Mahajan, Arpana; Sharma, Shashi

    2009-02-01

    Effect of abscisic acid (ABA) and polyamines (PAs) [putrescine (Put), spermidine (Spd) and spermine (Spm)] on mitosis in root tips of A. cepa was studied. Treatment with ABA (0.1 to 100 microM) for 24 hr suppressed the mitosis, measured as mitotic index (MI), in a concentration-dependent manner with approx. 50% suppression at 10 microM of ABA. Treatment with different PAs (1 to 100 microM) had differential mitosis suppression effect. Spm was most inhibitory followed by Spd and Put, respectively. The higher concentrations of PAs (1 mM Put; 0.1 and 1 mM Spd or Spm) caused cell distortion. Remarkably, a 24 hr pretreatment of root tips with PAs prior to ABA (100 microM) treatment resulted in a general concentration-dependent reversal of ABA-induced suppression of MI. Catalase (CAT) activity in the root tips, an indicator of redox metabolism, increased due to ABA treatment in a concentration-dependent manner, remained unaltered in response to Put and declined due to Spd and Spm (> or = 0.1 mM). However, all PAs, irrespective of their individual effects, generally antagonized the ABA-dependent increase in CAT activity. Data indicate the possibility of ABA-PA interaction in the regulation of mitosis.

  7. Suppression of newborn natural killer cell activity by prostaglandin E2

    SciTech Connect

    Milch, P.O.; Salvatore, W.; Luft, B.; Baker, D.A.

    1988-10-01

    The effect of prostaglandin E2 on natural killer cell activity of cord blood was examined. Natural killer cell activity, determined by chromium 51 release, was significantly reduced after prostaglandin E2 (1 microgram/ml) treatment. Prostaglandin E2 has been found to enhance the cellular spread of herpesvirus. Thus prostaglandins may enhance viral infections indirectly by suppressing natural killer cell activity.

  8. Adherence and Viral Suppression among Infants and Young Children Initiating Protease Inhibitor-Based Antiretroviral Therapy

    PubMed Central

    Teasdale, Chloe A; Abrams, Elaine J; Coovadia, Ashraf; Strehlau, Renate; Martens, Leigh; Kuhn, Louise

    2012-01-01

    Background High levels of adherence to antiretroviral therapy (ART) are considered necessary to achieve viral suppression. We analyzed data from a cohort of HIV-infected children who were less than 2 years of age receiving protease inhibitor (PI)-based ART to investigate associations between viral suppression and adherence ascertained using different methods. Methods Data were from the pre-randomization phase of a clinical trial in South Africa of HIV-infected children initiating either ritonavir-boosted lopinavir (LPV/r)- or ritonavir-based ART. At scheduled visits during the first 24 weeks of enrollment, study pharmacists measured quantities of medications returned (MR) to the clinic. Caregivers answered questionnaires on missed doses and adherence barriers. Associations between adherence and viral suppression (HIV-1 RNA <400 copies/mL) were investigated by regimen. Results By 24 weeks, 197/269 (73%) children achieved viral suppression. There was no association between viral suppression and caregiver reported missed doses or adherence barriers. For children receiving the LPV/r-based regimen, MR adherence to each of the three drugs in the regimen (LPV/r, lamivudine or stavudine) individually or together was associated with viral suppression at different adherence thresholds. For example, <85% adherence to any of the three medications significantly increased odds of lack of viral suppression (Odds Ratio [OR] 2.30 [95% CI: 1.30–4.07], p=.004). In contrast, for children receiving the ritonavir-based regimen, there was no consistent pattern of association between MR and viral suppression. Conclusions Caregiver reports of missed doses did not predict virologic response to treatment. Pharmacist medication reconciliation correlated strongly with virologic response for children taking a LPV/r-based regimen and appears to be a valid method for measuring pediatric adherence. PMID:23249913

  9. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

    PubMed

    Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

    2016-08-01

    Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy.

  10. Suppressive competition: how sounds may cheat sight.

    PubMed

    Kayser, Christoph; Remedios, Ryan

    2012-02-23

    In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior.

  11. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  12. Characterization of Immune Suppression Induced by Polyribonucleotides.

    DTIC Science & Technology

    1985-12-01

    RD-0162 482 CHARACTERIZATION OF IMMUNE SUPPRESSION INDUCED Y v i POLYRIDONUCLEOTIDES(U) MINNESOTA UNIV DULUTH DEPT OF MEDICAL MICROBIOLOGY AND...Polyribonucleotides by Marilyn J. Odean and Arthur G. Johnson Dept. of Medical Microbiology /Immunology University of Minnesota-Duluth 55812 DTICS ELECTE DEC 18

  13. Active suppression after involuntary capture of attention.

    PubMed

    Sawaki, Risa; Luck, Steven J

    2013-04-01

    After attention has been involuntarily captured by a distractor, how is it reoriented toward a target? One possibility is that attention to the distractor passively fades over time, allowing the target to become attended. Another possibility is that the captured location is actively suppressed so that attention can be directed toward the target location. The present study investigated this issue with event-related potentials (ERPs), focusing on the N2pc component (a neural measure of attentional deployment) and the Pd component (a neural measure of attentional suppression). Observers identified a color-defined target in a search array, which was preceded by a task-irrelevant cue array. When the cue array contained an item that matched the target color, this item captured attention (as measured both behaviorally and with the N2pc component). This capture of attention was followed by active suppression (indexed by the Pd component), and this was then followed by a reorienting of attention toward the target in the search array (indexed by the N2pc component). These findings indicate that the involuntary capture of attention by a distractor is followed by an active suppression process that presumably facilitates the subsequent voluntary orienting of attention to the target.

  14. Sound-suppressing structure with thermal relief

    NASA Technical Reports Server (NTRS)

    Nash, D. O.; Holowach, J. (Inventor)

    1978-01-01

    Sound-suppressing structure comprising stacked acoustic panels wherein the inner high frequency panel is mounted for thermal expansion with respect to the outer low frequency panel is discussed. Slip joints eliminate the potential for thermal stresses, and a thermal expansion gap between the panels provides for additional relative thermal growth while reducing heat convection into the low frequency panel.

  15. Suppressed Carrier Synchronizers for ISI Channels

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami M.; Simon, Marvin K.

    1996-01-01

    We demonstrate a class of suppressed carrier synchronization loops that are motivated by MAP estimation theory and in the presence of ISI outperform the conventional I-Q loop which is designed on the basis of zero ISI (wideband assumption). The measure of comparison used is the so-called.

  16. Radio science measurements with suppressed carrier

    NASA Astrophysics Data System (ADS)

    Asmar, S.; Divsalar, D.; Oudrhiri, K.; Hamkins, J.

    Radio Science started when it became apparent with early deep space missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. The type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use the Cramer-Rao bound (CRB). The CRB for suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of the CRB for non-ideal data wiping is an innovative method that is presented here. Some numerical results are provided for a coded system.

  17. Radio Science Measurements with Suppressed Carrier

    NASA Technical Reports Server (NTRS)

    Asmar, Sami; Divsalar, Dariush; Oudrhiri, Kamal

    2013-01-01

    Radio Science started when it became apparent with early Solar missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. Type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use Cramer-Rao bound (CRB). The CRB for the suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of CRB for non-ideal data wiping is an innovative method that presented here. Some numerical results are provided for coded system.

  18. Government Doublethink: Protection or Suppression in Information.

    ERIC Educational Resources Information Center

    Drake, Miriam A.

    2003-01-01

    Discusses regulations and actions related to government withholding, suppressing, and altering information since September 11, 2001. Topics include conflicting goals of an informed citizenry versus national security, science and technology progress versus protection of sensitive information, and public health versus ideology; political pressure;…

  19. Collective suppression of linewidths in circuit QED.

    PubMed

    Nissen, Felix; Fink, Johannes M; Mlynek, Jonas A; Wallraff, Andreas; Keeling, Jonathan

    2013-05-17

    We report the experimental observation and a theoretical explanation of collective suppression of linewidths for multiple superconducting qubits coupled to a good cavity. This demonstrates how strong qubit-cavity coupling can significantly modify the dephasing and dissipation processes that might be expected for individual qubits, and can potentially improve coherence times in many-body circuit QED.

  20. Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

    PubMed Central

    van Agtmaal, Maaike; van Os, Gera J.; Hol, W.H. Gera; Hundscheid, Maria P.J.; Runia, Willemien T.; Hordijk, Cornelis A.; de Boer, Wietse

    2015-01-01

    There is increasing evidence that microbial volatiles (VOCs) play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial community composition would affect the production by soils of VOCs suppressing the plant-pathogenic oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we compared the composition of bacterial communities in sandy soils that had been exposed to anaerobic disinfestation (AD), a treatment used to kill harmful soil organisms, with the composition in untreated soils. Three months after the AD treatment had been finished, there was still a clear legacy effect of the former anaerobic stress on bacterial community composition with a strong increase in relative abundance of the phylum Bacteroidetes and a significant decrease of the phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi, and Chlorobi. This change in bacterial community composition coincided with loss of production of Pythium suppressing soil volatiles (VOCs) and of suppression of Pythium impacts on Hyacinth root development. One year later, the composition of the bacterial community in the AD soils was reflecting that of the untreated soils. In addition, both production of Pythium-suppressing VOCs and suppression of Pythium in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS analysis identified several VOCs, among which compounds known to be antifungal, that were produced in the untreated soils but not in the AD soils. These compounds were again produced 15 months after the AD treatment. Our data indicate that soils exposed to a drastic stress can temporarily lose pathogen suppressive characteristics and that both loss and return of these suppressive characteristics coincides with shifts in the soil bacterial community composition. Our data are supporting the

  1. Spacecraft Fire Suppression: Testing and Evaluation

    NASA Technical Reports Server (NTRS)

    Abbud-Madrid, Angel; McKinnon, J. Thomas; Delplanque, Jean-Pierre; Kailasanath, Kazhikathra; Gokoglu, Suleyman; Wu, Ming-Shin

    2004-01-01

    The objective of this project is the testing and evaluation of the effectiveness of a variety of fire suppressants and fire-response techniques that will be used in the next generation of spacecraft (Crew Exploration Vehicle, CEV) and planetary habitats. From the many lessons learned in the last 40 years of space travel, there is common agreement in the spacecraft fire safety community that a new fire suppression system will be needed for the various types of fire threats anticipated in new space vehicles and habitats. To date, there is no single fire extinguishing system that can address all possible fire situations in a spacecraft in an effective, reliable, clean, and safe way. The testing conducted under this investigation will not only validate the various numerical models that are currently being developed, but it will provide new design standards on fire suppression that can then be applied to the next generation of spacecraft extinguishment systems. The test program will provide validation of scaling methods by conducting small, medium, and large scale fires. A variety of suppression methods will be tested, such as water mist, carbon dioxide, and nitrogen with single and multiple injection points and direct or distributed agent deployment. These injection methods cover the current ISS fire suppression method of a portable hand-held fire extinguisher spraying through a port in a rack and also next generation spacecraft units that may have a multi-point suppression delivery system built into the design. Consideration will be given to the need of a crew to clean-up the agent and recharge the extinguishers in flight in a long-duration mission. The fire suppression methods mentioned above will be used to extinguish several fire scenarios that have been identified as the most relevant to spaceflight, such as overheated wires, cable bundles, and circuit boards, as well as burning cloth and paper. Further testing will be conducted in which obstructions and

  2. Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation

    PubMed Central

    Taguchi, Kazumi; Kitamura, Hiroshi; Yasui, Takahiro; Naiki, Taku; Hamamoto, Shuzo; Ando, Ryosuke; Mizuno, Kentaro; Kawai, Noriyasu; Tozawa, Keiichi; Asano, Kenichi; Tanaka, Masato; Miyoshi, Ichiro; Kohri, Kenjiro

    2014-01-01

    We recently reported evidence suggesting that migrating macrophages (Mϕs) eliminate renal crystals in hyperoxaluric mice. Mϕs can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mϕ phenotype. M2Mϕs promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mϕs in renal crystal formation during hyperoxaluria using CSF-1–deficient mice, which lack M2Mϕs. Compared with wild-type mice, CSF-1–deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1–deficient and wild-type mice. Flow cytometry of sorted renal Mϕs showed that CSF-1 deficiency resulted in a smaller population of CD11b+F4/80+CD163+CD206hi cells, which represent M2-like Mϕs. Additionally, transfusion of M2Mϕs into CSF-1–deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mϕs than M1-polarized Mϕs or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation. PMID:24578130

  3. Bird assemblage response to restoration of fire-suppressed longleaf pine sandhills.

    PubMed

    Steen, David A; Conner, L M; Smith, Lora L; Provencher, Louis; Hiers, J Kevin; Pokswinski, Scott; Helms, Brian S; Guyer, Craig

    2013-01-01

    The ecological restoration of fire-suppressed habitats may require a multifaceted approach. Removal of hardwood trees together with reintroduction of fire has been suggested as a method of restoring fire-suppressed longleaf pine (Pinus palustris) forests; however, this strategy, although widespread, has not been evaluated on large spatial and temporal scales. We used a landscape-scale experimental design to examine how bird assemblages in fire-suppressed longleaf pine sandhills responded to fire alone or fire following mechanical removal or herbicide application to reduce hardwood levels. Individual treatments were compared to fire-suppressed controls and reference sites. After initial treatment, all sites were managed with prescribed fire, on an approximately two- to three-year interval, for over a decade. Nonmetric multidimensional scaling ordinations suggested that avian assemblages on sites that experienced any form of hardwood removal differed from assemblages on both fire-suppressed sites and reference sites 3-4 years after treatment (i.e., early posttreatment). After >10 years of prescribed burning on all sites (i.e., late posttreatment), only assemblages at sites treated with herbicide were indistinguishable from assemblages at reference sites. By the end of the study, individual species that were once indicators of reference sites no longer contributed to making reference sites unique. Occupancy modeling of these indicator species also demonstrated increasing similarity across treatments over time. Overall, although we documented long-term and variable assemblage-level change, our results indicate occupancy for birds considered longleaf pine specialists was similar at treatment and reference sites after over a decade of prescribed burning, regardless of initial method of hardwood removal. In other words, based on the response of species highly associated with the habitat, we found no justification for the added cost and effort of fire surrogates; fire

  4. OSCEE fan exhaust bulk absorber treatment evaluation

    NASA Technical Reports Server (NTRS)

    Bloomer, H. E.; Samanich, N. E.

    1980-01-01

    The acoustic suppression capability of bulk absorber material designed for use in the fan exhaust duct walls of the quiet clean short haul experiment engine (OCSEE UTW) was evaluated. The acoustic suppression to the original design for the engine fan duct which consisted of phased single degree-of-freedom wall treatment was tested with a splitter and also with the splitter removed. Peak suppression was about as predicted with the bulk absorber configuration, however, the broadband characteristics were not attained. Post test inspection revealed surface oil contamination on the bulk material which could have caused the loss in bandwidth suppression.

  5. Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining

    PubMed Central

    Liu, Yan; Li, Tong-Ruei R; Xu, Cong; Xu, Tian

    2016-01-01

    The increasing prevalence of obesity is closely related to excessive energy consumption. Clinical intervention of energy intake is an attractive strategy to fight obesity. However, the current FDA-approved weight-loss drugs all have significant side effects. Here we show that ribose upregulates gut motility and suppresses mice body weight gain. Ribokinase, which is encoded by Rbks gene, is the first enzyme for ribose metabolism in vivo. Rbks mutation resulted in ribose accumulation in the small intestine, which accelerated gut movement. Ribose oral treatment in wild type mice also enhanced bowel motility and rendered mice resistance to high fat diets. The suppressed weight gain was resulted from enhanced ingested food excretion. In addition, the effective dose of ribose didn't cause any known side effects (i.e. diarrhea and hypoglycemia). Overall, our results show that ribose can regulate gut motility and energy homeostasis in mice, and suggest that administration of ribose and its analogs could regulate gastrointestinal motility, providing a novel therapeutic approach for gastrointestinal dysfunction and weight control. PMID:27194947

  6. Suppression of cardiac alternans by alternating-period-feedback stimulations

    NASA Astrophysics Data System (ADS)

    Sridhar, S.; Le, Duy-Manh; Mi, Yun-Chieh; Sinha, Sitabhra; Lai, Pik-Yin; Chan, C. K.

    2013-04-01

    Alternans response, comprising a sequence of alternating long and short action potential durations in heart tissue, seen during rapid periodic pacing can lead to conduction block resulting in potentially fatal cardiac failure. A method of pacing with feedback control is proposed to reduce the alternans and therefore the probability of subsequent cardiac failure. The reduction is achieved by feedback control using small perturbations of constant magnitude to the original, alternans-generating pacing period T, viz., using sequences of two alternating periods of T+ΔT and T-ΔT, with ΔT≪T. Such a control scheme for alternans suppression is demonstrated experimentally in isolated whole heart experiments. This alternans suppression scheme is further confirmed and investigated in detail by simulations of ion-channel-based cardiac models both for a single cell and in one-dimensional spatially extended systems. The mechanism of the success of our method can be understood in terms of dynamics in phase space, viz., as the state of activity of the cell being confined within a narrow volume of phase space for the duration of control, resulting in extremely diminished variation in successive action potential durations. Our method is much more robust to noise than previous alternans reduction techniques based on fixed point stabilization and should thus be more efficient in terms of experimental implementation, which has implications for clinical treatment for arrhythmia.

  7. Sulfated glycosaminoglycans support osteoblast functions and concurrently suppress osteoclasts.

    PubMed

    Salbach-Hirsch, Juliane; Ziegler, Nicole; Thiele, Sylvia; Moeller, Stephanie; Schnabelrauch, Matthias; Hintze, Vera; Scharnweber, Dieter; Rauner, Martina; Hofbauer, Lorenz C

    2014-06-01

    In order to improve bone regeneration, development and evaluation of new adaptive biomaterials is warranted. Glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are major extracellular matrix (ECM) components of bone, and display osteogenic properties that are potentially useful for biomaterial applications. Using native and synthetic sulfate-modified GAGs, we manufactured artificial collagen/GAG ECM (aECMs) coatings, and evaluated how the presence of GAGs and their degree of sulfation affects the differentiation of murine mesenchymal stem cells to osteoblasts (OB) cultivated on these aECMs. GAG sulfation regulated osteogenesis at all key steps of OB development. Adhesion, but not migration, was diminished by 50% (P < 0.001). Proliferation and metabolic activity were slightly (P < 0.05) and cell death events strongly (P < 0.001) down-regulated due to a switch from proliferative to matrix synthesis state. When exposed to sulfated GAGs, OB marker genes, such as alkaline phosphatase, osteoprotegerin (OPG), and osteocalcin increased by up to 28-fold (P < 0.05) and calcium deposition up to 4-fold (P < 0.05). Furthermore, GAG treatment of OBs suppressed their ability to support osteoclast (OC) differentiation and resorption. In conclusion, GAG sulfation controls bone cell homeostasis by concurrently promoting osteogenesis and suppressing their paracrine support of OC functions, thus displaying a favorable profile on bone remodeling. Whether these cellular properties translate into improved bone regeneration needs to be validated in vivo.

  8. Epigallocatechin-gallate Suppresses Tumorigenesis by Directly Targeting Pin1

    SciTech Connect

    Urusova, Darya V.; Shim, Jung-Hyun; Kim, Dong Joon; Jung, Sung Keun; Zykova, Tatyana A.; Carper, Andria; Bode, Ann M.; Dong, Zigang

    2011-09-01

    The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate–induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.

  9. Piceatannol Suppresses endotoxin-induced ocular inflammation in Rats

    PubMed Central

    Kalariya, Nilesh M.; Shoeb, Mohammad; Reddy, Aramati B. M.; Sawhney, Rahul; Ramana, Kota V.

    2013-01-01

    Anti-inflammatory effect of piceatannol, a naturally occurring polyphenol and a potent free radical scavenger, on ocular inflammation is not known. We examined the anti-inflammatory role of piceatannol in ocular inflammatory response due to endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS; 150 ug/rat). Piceatannol (30 mg/kg body wt, i.p) was injected either 2 h prior to or 1 h post LPS induction. A significant increase in the number of infiltrating cells, total protein, and various cytokines and chemokines in AqH were observed in the EIU rat eyes as compared to control groups. However, pre- or post- treatment of piceatannol significantly blocked the LPS-induced changes. Further, piceatannol also suppressed the expression of Cox-2, iNOS and activation of NF-κB in the ciliary bodies as well as retina. Further, piceatannol also inhibited the expression of Cox-2, iNOS, and phosphorylation of NF-κB in primary human non-pigmented ciliary epithelial cells (HNPECs) treated with LPS. Similarly, piceatannol also diminished LPS-induced level of NO and PGE2 in HNPECs. Thus our results demonstrate an anti-inflammatory role of piceatannol in suppressing ocular inflammation induced by endotoxin in rats. PMID:23892029

  10. Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

    SciTech Connect

    Bagby, G.J.; Corll, C.B.; Martinez, R.R.

    1987-07-01

    Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.

  11. SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)

    PubMed Central

    He, Chang; Yu, Cheng-Rong; Mattapallil, Mary J.; Sun, Lin

    2016-01-01

    Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis. PMID:27703302

  12. Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis.

    PubMed

    Zhang, Kai; Ge, Zhenzhen; Da, Yurong; Wang, Dong; Liu, Ying; Xue, Zhenyi; Li, Yan; Li, Wen; Zhang, Lijuan; Wang, Huafeng; Zhang, Huan; Peng, Meiyu; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

    2014-08-15

    Plumbagin (PL, 5-hydroxy-2-methyl-1,4-naphthoquinone) is a herbal compound derived from medicinal plants of the Droseraceae, Plumbaginaceae, Dioncophyllaceae, and Ancistrocladaceae families. Reports have shown that PL exerts immunomodulatory activity and may be a novel drug candidate for immune-related disease therapy. However, its effects on dendritic cells (DCs), the most potent antigen-presenting cells (APCs), remain unclear. In this study, we demonstrate that PL inhibits the differentiation, maturation, and function of human monocyte-derived DCs. PL can also restrict the expression of Th1- and Th17-polarizing cytokines in mDC. In addition, PL suppresses DCs both in vitro and in vivo, as demonstrated by its effects on the mouse DC line DC2.4 and mice with experimental autoimmune encephalomyelitis (EAE), respectively. Notably, PL ameliorated the clinical symptoms of EAE, including central nervous system (CNS) inflammation and demyelination. Our results demonstrate the immune suppressive and anti-inflammatory properties of PL via its effects on DCs and suggest that PL could be a potential treatment for DC-related autoimmune and inflammatory diseases.

  13. Long-term suppression of infection in total joint arthroplasty.

    PubMed

    Rao, Nalini; Crossett, Lawrence S; Sinha, Raj K; Le Frock, Jack L

    2003-09-01

    Optimal treatment for a chronic infected prosthesis is the removal of infected and necrotic tissue and all the components of the prosthesis with staged revision in conjunction with systemic antibiotics. If this is not possible because of the poor general condition of the patient, because of unacceptable functional results secondary to removal of the prosthesis, or because the patient refuses surgery in an attempt to salvage the infected prosthesis, a reasonable alternative is long-term oral suppressive antibiotic therapy for maintenance of a functioning prosthesis. Prompt recognition with rapid debridement and initiation of antibiotic therapy seems crucial. Our study confirms a favorable outcome of maintenance of functioning prostheses in 86.2% of patients after a mean followup of 5 years. All patients had initial debridement with 4 to 6 weeks of systemic antibiotic therapy. Advanced age did not seem to predict poor outcome. Joint location, duration of symptoms, and the time of onset of infection did not predict success or failure. The overall success rate for Staphylococcus aureus prosthetic joint infection was 69% after a mean followup of 5 years. The ideal regimen and optimal duration of oral suppressive therapy for a favorable outcome is not well-established and needs additional data with prospective multicenter studies.

  14. Benchmark enclosure fire suppression experiments - phase 1 test report.

    SciTech Connect

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  15. Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters.

    PubMed

    Keung, W M; Vallee, B L

    1993-11-01

    Syrian Golden hamsters prefer and consume large and remarkably constant amounts of ethanol in a simple two-bottle free-choice regimen. Ethanol intake is significantly suppressed by zimelidine, bromocriptine, buspirone, and lithium carbonate, pharmacological agents that have been shown to be beneficial in controlling ethanol intake in alcohol-dependent humans. These results suggest that this ethanol-drinking animal model has high "predictive validity" and can be used effectively in the search for and identification of new agents for the treatment of alcohol abuse. The model has enabled us to confirm the putative antidipsotropic effect of Radix puerariae (RP), an herb long used in traditional Chinese medicine for the treatment of patients who abuse alcohol. A crude extract of RP at a dose of 1.5 g.kg-1 x day-1 significantly suppresses (> 50%) the free-choice ethanol intake of Golden hamsters. Moreover, two major constituents of RP, daidzein (4',7-dihydroxyisoflavone) and daidzin (the 7-glucoside of daidzein), were also shown to suppress free-choice ethanol intake. Daidzin and daidzein, at doses of 150 and 230 mg.kg-1 x day-1, respectively, suppress ethanol intake by > 50%. RP, daidzein, and daidzin treatment do not significantly affect the body weight and water or food intake of the hamsters. These findings identify a class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse.

  16. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes.

    PubMed

    Haseeb, Abdul; Ansari, Mohammad Yunus; Haqqi, Tariq M

    2017-02-01

    There is growing evidence in support of the involvement of inflammatory response in the pathogenesis of osteoarthritis (OA). Harpagoside, one of the bioactive components of Harpagophytum procumbens (Hp), has been shown to possess anti-inflammatory properties. Here we used an in vitro model of inflammation in OA to investigate the potential of harpagoside to suppress the production of inflammatory cytokines/chemokines such as IL-6 and matrix degrading proteases. We further investigated the likely targets of harpagoside in primary human OA chondrocytes. OA chondrocytes were pre-treated with harpagoside before stimulation with IL-1β. mRNA expression profile of 92 cytokines/chemokines was determined using TaqMan Human Chemokine PCR Array. Expression levels of selected mRNAs were confirmed using TaqMan assays. Protein levels of IL-6 and MMP-13 were assayed by ELISA and immunoblotting. Total protein levels and phosphorylation of signaling proteins were determined by immunoblotting. Cellular localization of IL-6 and c-Fos was performed by immunofluorescence and confocal microscopy. DNA binding activity of c-FOS/AP-1 was determined by ELISA. Harpagoside significantly altered the global chemokine expression profile in IL-1β-stimulated OA chondrocytes. Expression of IL-6 was highly induced by IL-1β, which was significantly inhibited by pre-treatment of OA chondrocytes with harpagoside. Harpagoside did not inhibit the IL-1β-induced activation of NF-κB and C/EBPβ transcription factors but suppressed the IL-1β-triggered induction, phosphorylation, and DNA binding activity of c-FOS, one of the main components of AP-1 transcription factors. Further, harpagoside significantly inhibited the expression of MMP-13 in OA chondrocytes under pathological conditions. siRNA-mediated knockdown of IL-6 resulted in suppressed expression and secretion of MMP-13 directly linking the role of IL-6 with MMP-13 expression. Taken together, the present study suggests that harpagoside exerts a

  17. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  18. Suppressing photochemical reactions with quantized light fields

    NASA Astrophysics Data System (ADS)

    Galego, Javier; Garcia-Vidal, Francisco J.; Feist, Johannes

    2016-12-01

    Photoisomerization, that is, a photochemical reaction leading to a change of molecular structure after absorption of a photon, can have detrimental effects such as leading to DNA damage under solar irradiation, or as a limiting factor for the efficiency of solar cells. Here, we show that strong coupling of organic molecules to a confined light mode can be used to strongly suppress photoisomerization, as well as other photochemical reactions, and thus convert molecules that normally show fast photodegradation into photostable forms. We find this to be especially efficient in the case of collective strong coupling, where the distribution of a single excitation over many molecules and the light mode leads to a collective protection effect that almost completely suppresses the photochemical reaction.

  19. Active flutter suppression using dipole filters

    NASA Technical Reports Server (NTRS)

    Srinathkumar, S.; Waszak, Martin R.

    1992-01-01

    By using traditional control concepts of gain root locus, the active suppression of a flutter mode of a flexible wing is examined. It is shown that the attraction of the unstable mode towards a critical system zero determines the degree to which the flutter mode can be stabilized. For control situations where the critical zero is adversely placed in the complex plane, a novel compensation scheme called a 'Dipole' filter is proposed. This filter ensures that the flutter mode is stabilized with acceptable control energy. The control strategy is illustrated by designing flutter suppression laws for an active flexible wing (AFW) wind-tunnel model, where minimal control effort solutions are mandated by control rate saturation problems caused by wind-tunnel turbulence.

  20. Suppressing photochemical reactions with quantized light fields

    PubMed Central

    Galego, Javier; Garcia-Vidal, Francisco J.; Feist, Johannes

    2016-01-01

    Photoisomerization, that is, a photochemical reaction leading to a change of molecular structure after absorption of a photon, can have detrimental effects such as leading to DNA damage under solar irradiation, or as a limiting factor for the efficiency of solar cells. Here, we show that strong coupling of organic molecules to a confined light mode can be used to strongly suppress photoisomerization, as well as other photochemical reactions, and thus convert molecules that normally show fast photodegradation into photostable forms. We find this to be especially efficient in the case of collective strong coupling, where the distribution of a single excitation over many molecules and the light mode leads to a collective protection effect that almost completely suppresses the photochemical reaction. PMID:27941754

  1. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  2. System for Suppressing Vibration in Turbomachine Components

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor); Provenza, Andrew J. (Inventor); Choi, Benjamin B. (Inventor); Bakhle, Milind A. (Inventor); Min, James B (Inventor); Stefko, George L. (Inventor); Kussmann, John A (Inventor); Fougere, Alan J (Inventor)

    2013-01-01

    Disclosed is a system for suppressing vibration and noise mitigation in structures such as blades in turbomachinery. The system includes flexible piezoelectric patches which are secured on or imbedded in turbomachinery blades which, in one embodiment, comprises eight (8) fan blades. The system further includes a capacitor plate coupler and a power transfer apparatus, which may both be arranged into one assembly, that respectively transfer data and power. Each of the capacitive plate coupler and power transfer apparatus is configured so that one part is attached to a fixed member while another part is attached to a rotatable member with an air gap there between. The system still further includes a processor that has 16 channels, eight of which serve as sensor channels, and the remaining eight, serving as actuation channels. The processor collects and analyzes the sensor signals and, in turn, outputs corrective signals for vibration/noise suppression of the turbine blades.

  3. Immersion diuresis without expected suppression of vasopressin

    NASA Technical Reports Server (NTRS)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  4. Adaptive Suppression of Noise in Voice Communications

    NASA Technical Reports Server (NTRS)

    Kozel, David; DeVault, James A.; Birr, Richard B.

    2003-01-01

    A subsystem for the adaptive suppression of noise in a voice communication system effects a high level of reduction of noise that enters the system through microphones. The subsystem includes a digital signal processor (DSP) plus circuitry that implements voice-recognition and spectral- manipulation techniques. The development of the adaptive noise-suppression subsystem was prompted by the following considerations: During processing of the space shuttle at Kennedy Space Center, voice communications among test team members have been significantly impaired in several instances because some test participants have had to communicate from locations with high ambient noise levels. Ear protection for the personnel involved is commercially available and is used in such situations. However, commercially available noise-canceling microphones do not provide sufficient reduction of noise that enters through microphones and thus becomes transmitted on outbound communication links.

  5. Adaptive Modal Identification for Flutter Suppression Control

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.; Drew, Michael; Swei, Sean S.

    2016-01-01

    In this paper, we will develop an adaptive modal identification method for identifying the frequencies and damping of a flutter mode based on model-reference adaptive control (MRAC) and least-squares methods. The least-squares parameter estimation will achieve parameter convergence in the presence of persistent excitation whereas the MRAC parameter estimation does not guarantee parameter convergence. Two adaptive flutter suppression control approaches are developed: one based on MRAC and the other based on the least-squares method. The MRAC flutter suppression control is designed as an integral part of the parameter estimation where the feedback signal is used to estimate the modal information. On the other hand, the separation principle of control and estimation is applied to the least-squares method. The least-squares modal identification is used to perform parameter estimation.

  6. PUMA Suppresses Intestinal Tumorigenesis in Mice

    PubMed Central

    Qiu, Wei; Carson-Walter, Eleanor B.; Kuan, Shih Fan; Zhang, Lin; Yu, Jian

    2010-01-01

    Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of β-catenin hotspot mutations. The absence of PUMA led to a significantly elevated incidence of precursor lesions induced by AOM. AOM was found to induce p53-dependent PUMA expression and PUMA-dependent apoptosis in the colonic crypts and stem cell compartment. Furthermore, PUMA deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of APCMin/+ mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice. PMID:19491259

  7. Immune-suppressive activity of punicalagin via inhibition of NFAT activation

    SciTech Connect

    Lee, Sang-Ik; Kim, Byoung-Soo; Kim, Kyoung-Shin; Lee, Samkeun; Shin, Kwang-Soo; Lim, Jong-Soon

    2008-07-11

    Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.

  8. Endogenous central suppressive mechanisms regulating cough as potential targets for novel antitussive therapies.

    PubMed

    Mazzone, Stuart B; McGovern, Alice E; Farrell, Michael J

    2015-06-01

    Cough and the accompanying sensation known as the urge-to-cough are complex neurobiological phenomena dependent on sensory and motor neural processing at many levels of the neuraxis. In addition to the excitatory neural circuits that provide the positive drive for inducing cough and the urge-to-cough, recent studies have highlighted the existence of likely inhibitory central neural processes that can be engaged to suppress cough sensorimotor processing. In many respects, the balance between excitatory and inhibitory central cough control may be a critical determinant of cough in health and disease which argues for the importance of understanding the biology of these putative central inhibitory processes. This brief review summarises the current knowledge of the central circuits that govern voluntary and involuntary cough suppression and posits the notion of targeting central suppressive mechanisms as a treatment for disordered cough in disease.

  9. Suppression of 19S proteasome subunits marks emergence of an altered cell state in diverse cancers.

    PubMed

    Tsvetkov, Peter; Sokol, Ethan; Jin, Dexter; Brune, Zarina; Thiru, Prathapan; Ghandi, Mahmoud; Garraway, Levi A; Gupta, Piyush B; Santagata, Sandro; Whitesell, Luke; Lindquist, Susan

    2017-01-10

    The use of proteasome inhibitors to target cancer's dependence on altered protein homeostasis has been greatly limited by intrinsic and acquired resistance. Analyzing data from thousands of cancer lines and tumors, we find that those with suppressed expression of one or more 19S proteasome subunits show intrinsic proteasome inhibitor resistance. Moreover, such proteasome subunit suppression is associated with poor outcome in myeloma patients, where proteasome inhibitors are a mainstay of treatment. Beyond conferring resistance to proteasome inhibitors, proteasome subunit suppression also serves as a sentinel of a more global remodeling of the transcriptome. This remodeling produces a distinct gene signature and new vulnerabilities to the proapoptotic drug, ABT-263. This frequent, naturally arising imbalance in 19S regulatory complex composition is achieved through a variety of mechanisms, including DNA methylation, and marks the emergence of a heritably altered and therapeutically relevant state in diverse cancers.

  10. Incontinence Treatment: Surgical Treatments

    MedlinePlus

    ... Bowel Incontinence Signs & Symptoms Symptoms of Incontinence Diarrhea Treatment Lifestyle Changes Dietary Tips Medication Bowel Management Biofeedback Surgical Treatments Newer Treatment Options Tips on Finding a Doctor ...

  11. Follistatin-like protein 1 suppressed pro-inflammatory cytokines expression during neuroinflammation induced by lipopolysaccharide.

    PubMed

    Cheng, Kai-Yuan; Liu, Yi; Han, Ying-Guang; Li, Jing-Kun; Jia, Jia-Lin; Chen, Bin; Yao, Zhi-Xiao; Nie, Lin; Cheng, Lei

    2017-04-01

    Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment. FSTL1 suppressed upregulation of pro-inflammatory cytokines in astrocytes after LPS treatment. Moreover, FSTL1 downregulated expression of pro-inflammatory cytokines through suppressing MAPK/p-ERK1/2 pathway in astrocytes. Our results suggest that FSTL1 may play an anti-inflammatory role in neuroinflammation mediated by astrocytes.

  12. Effect of weighting on time sidelobe suppression

    NASA Technical Reports Server (NTRS)

    Dicenzo, A.

    1978-01-01

    Weighting simulations in the time domain were considered to shape the time-compressed pulse waveform. The digital input radar data were 32 bit I,Q, and simulated data from a point target, imaged by a Seasat-A type system. Weighting functions tested include stepped-amplitude distributions, (with 1 through 5 steps), and the cosine-squared plus pedestal distribution. Effects treated include mainlobe ratio, signal to noise ratio, and nearest sidelobe suppression.

  13. Analysis and Evaluation of Suppressive Shields

    DTIC Science & Technology

    1977-06-01

    resistance of the shield to fragment penetration, and 7. attenuation of thermal effects by the shield . Other aspects of the design include problems of entry...propellant, 2. methods to predict the thermal environment outside of a suppressive shield , 3. comparisons between measured and predicted pressures... SHIELDS by P. A. Co- x P. S. Westine CD J. J. Kulesz L.LJ E. D. Espurza c-.- January 1978 SOUTHWEST RESEARCH INSTITUTE Post Office Drawer 28510, 6220

  14. Investigation of refracting flows for acoustic suppression

    NASA Technical Reports Server (NTRS)

    Sloan, D.; Purves, R. B.; Farquhar, B. W.

    1977-01-01

    An experimental program to determine the possibility of using refracting flows for the suppression of aircraft inlet noise has been completed. Observations of wave behavior in accelerating duct flows have suggested that acoustic wave refraction could be used to direct inlet noise away from the ground upward to where it causes less annoyance. Measurements have also shown that acoustic wave refraction can cause large improvements in the effectiveness of acoustic lining material.

  15. [Cancer immunotherapy. Importance of overcoming immune suppression].

    PubMed

    Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

    2010-01-01

    Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.

  16. Fire suppression in human-crew spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Dietrich, Daniel L.

    1991-01-01

    Fire extinguishment agents range from water and foam in early-design spacecraft (Halon 1301 in the present Shuttle) to carbon dioxide proposed for the Space Station Freedom. The major challenge to spacecraft fire extinguishment design and operations is from the micro-gravity environment, which minimizes natural convection and profoundly influences combustion and extinguishing agent effectiveness, dispersal, and post-fire cleanup. Discussed here are extinguishment in microgravity, fire-suppression problems anticipated in future spacecraft, and research needs and opportunities.

  17. FGF Suppresses Poldip2 Expression in Osteoblasts.

    PubMed

    Katsumura, Sakie; Izu, Yayoi; Yamada, Takayuki; Griendling, Kathy; Harada, Kiyoshi; Noda, Masaki; Ezura, Yoichi

    2016-12-05

    Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modern world. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cell migration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cells were not known. Therefore, we examined the Poldip2 mRNA expression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulation was investigated in these cells. FGF suppressed the expression of Poldip2 in MC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed the migration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. J. Cell. Biochem. 9999: 1-8, 2017. © 2016 Wiley Periodicals, Inc.

  18. Effect of Wenxin Keli and Quinidine to Suppress Arrhythmogenesis in an Experimental Model of Brugada Syndrome

    PubMed Central

    Minoura, Yoshino; Panama, Brian K.; Nesterenko, Vladislav V.; Betzenhauser, Matthew; Barajas-Martínez, Hector; Hu, Dan; Di Diego, José M.; Antzelevitch, Charles

    2013-01-01

    Background Wenxin Keli (WK), a Chinese herb extract, is reported to be effective in the treatment of atrial and ventricular cardiac arrhythmias. Recent studies suggest that WK inhibits the transient outward current (Ito). Objective The present study examines the effectiveness of WK, alone and in combination with quinidine, to suppress arrhythmogenesis in an experimental model of Brugada syndrome (BrS). Methods and Results Action potential and ECG recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (10–15 μM) was used to pharmacologically mimic a genetic predisposition to BrS. The Ito agonist induced Phase 2 reentry (P2R) in 13/19 preparations and polymorphic ventricular tachycardia (pVT) in 11/19 wedge preparations. WK (10g/L) suppressed P2R and pVT in 100% (3/3) of preparations. A lower concentration of WK (5g/L) suppressed P2R in 60% (3/5) and pVT in 50% (2/4), but in combination with a low concentration of quinidine (5 μM) was 100% effective in suppressing P2R and pVT. Quinidine alone suppressed P2R and pVT in 60% (3/5) and 50% (2/4), respectively and in combination with WK (5g/L) suppressed P2R and pVT by 80% (4/5) and 75% (3/4), respectively. WK reduced Ito, ICa and contractility in single cardiomyocytes, but dose-dependently increased contractility in intact wedge preparations, an effect mimicked by tyramine. Conclusions Our data provide support for the hypothesis that Wenxin Keli, particularly in combination with quinidine, effectively suppresses arrhythmogenesis in an experimental model of BrS via inhibition of Ito and indirect adrenergic sympathomimetic effects. PMID:23499631

  19. Lenalidomide potentiates CD4(+)CD25(+)Treg-related suppression of lymphoma B-cell proliferation.

    PubMed

    Grygorowicz, Monika Anna; Borycka, Ilona Sara; Nowak, Eliza; Paszkiewicz-Kozik, Ewa; Rymkiewicz, Grzegorz; Błachnio, Katarzyna; Biernacka, Marzena; Bujko, Mateusz; Walewski, Jan; Markowicz, Sergiusz

    2016-03-10

    We have previously found that ex vivo expanded human CD4(+)CD25(+)Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4(+)CD25(+)Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4(+)CD25(+)T cells or CD4(+)CD25(+)CD127(lo)T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with "third-party" allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4(+)CD25(+)Tregs or CD4(+)CD25(+)CD127(lo)Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide.

  20. Suppression of Ostwald Ripening by Chemical Reactions

    NASA Astrophysics Data System (ADS)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-03-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable and coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Ostwald ripening must thus be suppressed to stabilize emulsions, e.g. to control the properties of pharmaceuticals, food, or cosmetics. Suppression of Ostwald ripening is also important in biological cells, which contain stable liquid-like compartments, e.g. germ granules, Cajal-bodies, and centrosomes. Such systems are often driven away from equilibrium by chemical reactions and can thus be called active emulsions. Here, we show that non-equilibrium chemical reactions can suppress Ostwald Ripening, leading to stable, monodisperse emulsions. We derive analytical approximations of the typical droplet size, droplet count, and time scale of the dynamics from a coarse-grained description of the droplet dynamics. We also compare these results to numerical simulations of the continuous concentration fields. Generally, we thus show how chemical reactions can be used to stabilize emulsions and to control their properties in technology and nature.

  1. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  2. Neural Networks for Mindfulness and Emotion Suppression.

    PubMed

    Murakami, Hiroki; Katsunuma, Ruri; Oba, Kentaro; Terasawa, Yuri; Motomura, Yuki; Mishima, Kazuo; Moriguchi, Yoshiya

    2015-01-01

    Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  3. Surface state transport suppression in topological insulators

    NASA Astrophysics Data System (ADS)

    Reijnders, Anjan A.; Tian, Y.; Pohl, G.; Kivlichan, I. D.; Zhao, S. Y. Frank; Kim, Y.-J.; Jia, S.; Cava, R. J.; Kwok, D. C.; Lee, N.; Cheong, S. W.; Burch, Kenneth S.

    2013-03-01

    An unresolved question in experimental research on topological insulators (TI) is the suppression mechanism of a TI's surface state transport. While room temperature ARPES studies reveal clear evidence of surface states, their observation in transport measurements is limited to low temperatures. A better understanding of this suppression is of fundamental interest, and crucial for pushing the boundary of device applications towards room-temperature operation. In this talk, we report the temperature dependent optical properties of the topological insulator Bi2Te2Se (BTS), obtained by infrared spectroscopy and ellipsometry, probing surface and bulk states simultaneously. We see clear evidence of coherent surface state transport at low temperature and find that electron-phonon coupling causes the gradual suppression of surface state transport as temperature rises to 43K. In the bulk, electron-phonon coupling enables the emergence of an indirect band gap transition, which peaks at 43K, and is limited by thermal ionization of the bulk valance band above 43K. For comparison with other resistive TIs, we also discuss the optical properties to BiSbSe2Te. Financially supported by NSERC CRSNG, Ontario Research Fund, Canadian Foundation for Innovation, Prins Bernhard Cultuurfonds, NSF

  4. Atomic clocks with suppressed blackbody radiation shift.

    PubMed

    Yudin, V I; Taichenachev, A V; Okhapkin, M V; Bagayev, S N; Tamm, Chr; Peik, E; Huntemann, N; Mehlstäubler, T E; Riehle, F

    2011-07-15

    We develop a concept of atomic clocks where the blackbody radiation shift and its fluctuations can be suppressed by 1-3 orders of magnitude independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies ν1 and ν2) which are exposed to the same thermal environment, there exists a "synthetic" frequency ν(syn) ∝ (ν1 - ε12ν2) largely immune to the blackbody radiation shift. For example, in the case of 171Yb+ it is possible to create a synthetic-frequency-based clock in which the fractional blackbody radiation shift can be suppressed to the level of 10(-18) in a broad interval near room temperature (300±15  K). We also propose a realization of our method with the use of an optical frequency comb generator stabilized to both frequencies ν1 and ν2, where the frequency ν(syn) is generated as one of the components of the comb spectrum.

  5. Hippocampal leptin suppresses methamphetamine-induced hyperlocomotion.

    PubMed

    Nishio, Masahiro; Watanabe, Yasuhiro

    2010-10-01

    Leptin is an anorexigenic peptide which is synthesized in white adipose tissue. The actions of leptin are mediated by the leptin receptor which is abundantly localized in the hypothalamus and is involved in energy regulation and balance. Recently, there has been evidence suggesting that the leptin receptor is also present in the hippocampus and may be involved with hippocampal excitability and long-term depression. To investigate the physiological function of leptin signalling in the hippocampus, we studied the effects of leptin on methamphetamine-induced ambulatory hyperactivity by utilizing intra-hippocampal infusion (i.h.) in mice. Our results show that the infusion of leptin (5 ng each bilaterally i.h.) does not affect the basal ambulatory activity but significantly suppresses methamphetamine-induced ambulatory hyperactivity as compared to saline-infused controls. Interestingly, higher dose of leptin increases the suppression of the methamphetamine-induced ambulatory hyperactivity. The i.h. infusion of leptin did not activate the JAK-STAT pathway, which is the cellular signalling pathway through which leptin acts in the hypothalamus. The infusion of leptin also did not affect activation of p42/44 MAPK which is known to be another leptin-induced signalling pathway in the brain. These results demonstrate that leptin has a novel potential suppressive effect on methamphetamine-induced hyperlocomotion and also suggest that there must be an alternative pathway in the hippocampus through which leptin signalling is being mediated.

  6. Suppression of Marangoni Convection in Float Zones

    NASA Technical Reports Server (NTRS)

    Dressler, R. F.

    1985-01-01

    The basic purpose of this program is to demonstrate by means of an Earth-based 1-g experiment that the undesirable Marangoni (surface tension) convection can be suppressed or significantly reduced by means of gas jets directed tangentially to the free surface of the liquid in a float zone. These jets will establish the tangential shear stress field over the surface which must be adjusted to equal the counter-stress resultant of the Marangoni shear stress which causes the convection. For proposed materials processing in space (o-g), particularly of important, highly reactive semiconductor materials, e.g., silicon, microgravity will virtually eliminate the unwanted thermal-buoyancy convection in the liquid silicon, but will have no effect in reducing the Marangoni convection. Unless this can be sufficiently suppressed by other means, there may be no significant advantages to the proposed space processing of reactive semiconductors. Although some inert gas such as argon must be used for the corrosive liquid silicon, the Earth-based experiment uses air jets and various transparent oils, since the basic principle involved is the same. The first float zone is enclosed in a very small rectangular box with a quasi-planar free surface. Stable Marangoni convection has been achieved and velocities measured photographically. The air jet system with variable velocity and temperature is under construction. Three independent parameters must be optimized to attain maximum suppression: the gas velocity, angle of attack, and gas temperature.

  7. Glucocorticoids suppress bone formation via the osteoclast.

    PubMed

    Kim, Hyun-Ju; Zhao, Haibo; Kitaura, Hideki; Bhattacharyya, Sandip; Brewer, Judson A; Muglia, Louis J; Ross, F Patrick; Teitelbaum, Steven L

    2006-08-01

    The pathogenesis of glucocorticoid-induced (GC-induced) bone loss is unclear. For example, osteoblast apoptosis is enhanced by GCs in vivo, but they stimulate bone formation in vitro. This conundrum suggests that an intermediary cell transmits a component of the bone-suppressive effects of GCs to osteoblasts in the intact animal. Bone remodeling is characterized by tethering of the activities of osteoclasts and osteoblasts. Hence, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To define the direct impact of GCs on bone-resorptive cells, we compared the effects of dexamethasone (DEX) on WT osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells (GRoc-/- mice). While the steroid prolonged longevity of osteoclasts, their bone-degrading capacity was suppressed. The inhibitory effect of DEX on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. DEX specifically arrested M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances GRoc-/- mice were spared the impact of DEX on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of DEX, GRoc-/- mice are protected from the steroid's inhibition of bone formation.

  8. Conditionals, Context, and the Suppression Effect.

    PubMed

    Cariani, Fabrizio; Rips, Lance J

    2016-02-01

    Modus ponens is the argument from premises of the form If A, then B and A to the conclusion B (e.g., from If it rained, Alicia got wet and It rained to Alicia got wet). Nearly all participants agree that the modus ponens conclusion logically follows when the argument appears in this Basic form. However, adding a further premise (e.g., If she forgot her umbrella, Alicia got wet) can lower participants' rate of agreement-an effect called suppression. We propose a theory of suppression that draws on contemporary ideas about conditional sentences in linguistics and philosophy. Semantically, the theory assumes that people interpret an indicative conditional as a context-sensitive strict conditional: true if and only if its consequent is true in each of a contextually determined set of situations in which its antecedent is true. Pragmatically, the theory claims that context changes in response to new assertions, including new conditional premises. Thus, the conclusion of a modus ponens argument may no longer be accepted in the changed context. Psychologically, the theory describes people as capable of reasoning about broad classes of possible situations, ordered by typicality, without having to reason about individual possible worlds. The theory accounts for the main suppression phenomena, and it generates some novel predictions that new experiments confirm.

  9. BAER suppression during posterior fossa dural opening

    PubMed Central

    Shields, Christopher B.; Shields, Lisa B. E.; Jiang, Yi Dan; Yao, Tom; Zhang, Yi Ping; Sun, David A.

    2015-01-01

    Background: Intraoperative monitoring with brainstem auditory evoked responses (BAER) provides an early warning signal of potential neurological injury and may avert tissue damage to the auditory pathway or brainstem. Unexplained loss of the BAER signal in the operating room may present a dilemma to the neurosurgeon. Methods: This paper documents two patients who displayed a unique mechanism of suppression of the BAER apparent within minutes following dural opening for resection of a posterior fossa meningioma. Results: In two patients with anterior cerebellopontine angle and clival meningiomas, there was a significant deterioration of the BAER soon after durotomy but prior to cerebellar retraction and tumor removal. Intracranial structures in the posterior fossa lying between the tumor and dural opening were shifted posteriorly after durotomy. Conclusion: We hypothesized that the cochlear nerve and vessels entering the acoustic meatus were compressed or stretched when subjected to tissue shift. This movement caused cochlear nerve dysfunction that resulted in BAER suppression. BAER was partially restored after the tumor was decompressed, dura repaired, and bone replaced. BAER was not suppressed following durotomy for removal of a meningioma lying posterior to the cochlear complex. Insight into the mechanisms of durotomy-induced BAER inhibition would allay the neurosurgeon's anxiety during the operation. PMID:25883849

  10. Suppressive effects of 3-bromopyruvate on the proliferation and the motility of hepatocellular carcinoma cells.

    PubMed

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    The compound 3-bromopyruvate (3BP) is an analogue of pyruvate, which is the final product of glycolysis that enters the citric acid cycle. The present study aimed to investigate the suppressive effects of 3BP on the proliferation and motility of hepatocellular carcinoma (HCC) cells. HLF and PLC/PRF/5 cells were cultured with 3BP and subjected to an MTS assay. Apoptosis was analyzed by hematoxylin and eosin staining. Cell motility was analyzed using a scratch assay. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expression levels of cyclin D1 and matrix metalloproteinase (MMP)9. Proliferation of both cell lines was significantly suppressed by 3BP at 100 µM (P<0.05). The expression level of cyclin D1 was decreased after 3BP treatment at 100 µM in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with 3BP at 100 µM. These results revealed that 3BP suppressed cell proliferation, decreased the expression of cyclin D1, and induced apoptosis in HCC cells. 3BP significantly suppressed motility in both cell lines (P<0.05). The expression level of MMP9 was significantly decreased (P<0.05). 3BP suppressed the proliferation and motility of HCC cells by decreasing the expression of cyclin D1 and MMP9.

  11. Suppressive effects of 3-methylcholanthrene on the in vitro antitumor activity of naturally cytotoxic cells

    SciTech Connect

    Lill, P.H.; Gangemi, D.

    1986-01-01

    Transient suppression of splenic natural killer (NK), natural cytotoxic (NC) and peritoneal macrophage cytotoxicity was observed following a single injection of 3-methylcholanthrene (3-MC) into C3H/HeN mice. Natural killer cell activity was depressed by 30-60% 4-6 d after injection of 1.0 mg 3-MC. Levels of NK reactivity returned to normal 8 d post 3-MC injection, and no suppression of natural killing was seen when tested 6 wk after 3-MC treatment. 3-MC did not affect propionibacterium acnes augmentation of NK cell activity when tested both 6 d and 6 wk after carcinogen injection. The results indicate that the observed suppression of naturally cytotoxic cells may not be important in allowing 3-MC-induced tumors to grow, since suppression is not long-lasting. Therefore, any effect on tumor growth mediated by a suppression of naturally cytotoxic cells would have to be exerted at the earliest stages of tumor development.

  12. Growth suppression by ursodeoxycholic acid involves caveolin-1 enhanced degradation of EGFR

    PubMed Central

    Feldman, Rebecca; Martinez, Jesse D.

    2009-01-01

    Summary Ursodeoxycholic acid (UDCA) has been shown to prevent colon tumorigenesis in animal models and in humans. In vitro work indicates that this bile acid can suppress cell growth and mitogenic signaling suggesting that UDCA may be an anti-proliferative agent. However, the mechanism by which UDCA functions is unclear. Previously we showed that bile acids may alter cellular signaling by acting at the plasma membrane. Here we utilized EGFR as a model membrane receptor and examined the effects that UDCA has on its functioning. We found that UDCA promoted an interaction between EGFR and caveolin-1 and this interaction enhanced UDCA-mediated suppression of MAP kinase activity and cell growth . Importantly, UDCA treatment led to recruitment of the ubiquitin ligase, c-Cbl, to the membrane, ubiquitination of EGFR, and increased receptor degradation. Moreover, suppression of c-Cbl activity abrogated UDCA's growth suppression activities suggesting that receptor ubiquitination plays an important role in UDCA's biological activities. Taken together these results suggest that UDCA may act to suppress cell growth by inhibiting the mitogenic activity of receptor tyrosine kinases such as EGFR through increased receptor degradation. PMID:19446582

  13. Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

    PubMed Central

    Detweiler, Mark B.; Pagadala, Bhuvaneshwar; Candelario, Joseph; Boyle, Jennifer S.; Detweiler, Jonna G.; Lutgens, Brian W.

    2016-01-01

    The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares. PMID:27999253

  14. Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center.

    PubMed

    Detweiler, Mark B; Pagadala, Bhuvaneshwar; Candelario, Joseph; Boyle, Jennifer S; Detweiler, Jonna G; Lutgens, Brian W

    2016-12-16

    The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0-6.0 mg), clonidine (63%, 0.1-2.0 mg), quetiapine (50%, 12.5-800.0 mg), mirtazapine (50%; 7.5-30.0 mg), and terazosin (64%, 50.0-300.0 mg). Notably, olanzapine (2.5-10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares.

  15. Randomized controlled trials of psychological and pharmacological treatments for nightmares: a meta-analysis.

    PubMed

    Augedal, Aslak Wøien; Hansen, Kenneth Schøld; Kronhaug, Christian Robstad; Harvey, Allison G; Pallesen, Ståle

    2013-04-01

    A meta-analysis of treatments for nightmares is reported. The studies were identified by database searches and by an inspection of relevant reference lists. The inclusion criteria were: nightmares as a target problem, studies published in English, use of a randomized controlled trials and reporting of nightmare-relevant outcomes. A total of 19 studies, published between 1978 and 2012 were identified, which included 1285 participants. Effect sizes were calculated as Cohen's d. A statistically significant improvement for all studies combined (d = 0.47, 95% CI = 0.33-0.60, fixed effects model; d = 0.49, 95% CI = 0.32-0.66, random effects model) and for psychological treatments alone (d = 0.48, 95% CI = 0.36-0.60, random) and for prazosin alone (d = 0.50, 95% CI = 0.03-0.96, random) was found. Individual therapy format yielded a higher effect size than a self-help format (p = 0.03). Minimal interventions (relaxation, recording) yielded lower overall effect size than studies offering more extensive interventions (p = 0.02). It is concluded that there are both psychological and pharmacological interventions which have documented effects for the treatment of nightmares.

  16. System and method for suppressing sublimation using opacified aerogel

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeff S. (Inventor); Snyder, G. Jeffrey (Inventor); Calliat, Thierry (Inventor); Fleurial, Jean-Pierre (Inventor); Jones, Steven M. (Inventor); Palk, Jong-Ah (Inventor)

    2008-01-01

    The present invention relates to a castable, aerogel-based, ultra-low thermal conductivity opacified insulation to suppress sublimation. More specifically, the present invention relates to an aerogel opacified with various opacifying or reflecting constituents to suppress sublimation and provide thermal insulation in thermoelectric modules. The opacifying constituent can be graded within the aerogel for increased sublimation suppression, and the density of the aerogel can similarly be graded to achieve optimal thermal insulation and sublimation suppression.

  17. Coating Thermoelectric Devices To Suppress Sublimation

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

    2007-01-01

    A technique for suppressing sublimation of key elements from skutterudite compounds in advanced thermoelectric devices has been demonstrated. The essence of the technique is to cover what would otherwise be the exposed skutterudite surface of such a device with a thin, continuous film of a chemically and physically compatible metal. Although similar to other sublimation-suppression techniques, this technique has been specifically tailored for application to skutterudite antimonides. The primary cause of deterioration of most thermoelectric materials is thermal decomposition or sublimation - one or more elements sublime from the hot side of a thermoelectric couple, changing the stoichiometry of the device. Examples of elements that sublime from their respective thermoelectric materials are Ge from SiGe, Te from Pb/Te, and now Sb from skutterudite antimonides. The skutterudite antimonides of primary interest are CoSb3 [electron-donor (n) type] and CeFe(3-x)Co(x)Sb12 [electron-acceptor (p) type]. When these compounds are subjected to typical operating conditions [temperature of 700 C and pressure <10(exp -5) torr (0.0013 Pa)], Sb sublimes from their surfaces, with the result that Sb depletion layers form and advance toward their interiors. As the depletion layer advances in a given device, the change in stoichiometry diminishes the thermal-to-electric conversion efficiency of the device. The problem, then, is to prevent sublimation, or at least reduce it to an acceptably low level. In preparation for an experiment on suppression of sublimation, a specimen of CoSb3 was tightly wrapped in a foil of niobium, which was selected for its chemical stability. In the experiment, the wrapped specimen was heated to a temperature of 700 C in a vacuum of residual pressure <10(exp -5) torr (0.0013 Pa), then cooled and sectioned. Examination of the sectioned specimen revealed that no depletion layer had formed, indicating the niobium foil prevented sublimation of antimony at 700 C

  18. Topiramate + phentermine. An excessively dangerous appetite-suppressant combination.

    PubMed

    2013-03-01

    The cornerstones of treatment for obesity, and even more so for simple overweight, are dietary measures and physical exercise. There are no drugs with a favourable harm-benefit balance in this setting. A fixed-dose combination of topiramate, an antiepileptic drug, and phentermine, an appetite-suppressant amphetamine, has been refused marketing authorisation in the European Union, after being licensed in the United States. There are no randomised controlled trials of topiramate + phentermine in the prevention of complications of obesity. In the three available placebo-controlled trials, patients treated with topiramate 46 mg per day + phentermine 7.5 mg per day for between 1 and 2 years lost about 6-8 kg more than patients who received a placebo. About one-quarter of this weight loss was regained within a year after treatment discontinuation. The known adverse effects of the two drugs composing this combination are additive, and include psychiatric disorders, cardiac arrhythmias and metabolic acidosis. The risk of serious cardiovascular disorders was not adequately studied during clinical trials. Many women of child-bearing age would be exposed to this combination, which can provoke fetal abnormalities, including cleft palate, if taken during pregnancy. In practice, the topiramate + phentermine combination has an unfavourable harm-benefit balance and has no place in the treatment of obesity.

  19. Parthenolide suppresses pancreatic cell growth by autophagy-mediated apoptosis

    PubMed Central

    Liu, Weifeng; Wang, Xinshuai; Sun, Junjun; Yang, Yanhui; Li, Wensheng; Song, Junxin

    2017-01-01

    Pancreatic cancer is an aggressive malignancy and is unresponsive to conventional chemotherapies. Parthenolide, a sesquiterpene lactone isolated from feverfew, has exhibited potent anticancer effects against various cancers. The purpose of this report was to investigate the effect and underlying mechanism of parthenolide in human pancreatic cancer Panc-1 and BxPC3 cells. The results demonstrated that parthenolide suppressed the growth and induced apoptosis of Panc-1 and BxPC3 pancreatic cancer cells with the half maximal inhibitory concentration (IC50) ranging between 7 and 9 μM after 24 h of treatment. Significant autophagy was induced by parthenolide treatment in pancreatic cancer cells. Parthenolide treatment concentration-dependently increased the percentage of autophagic cells and significantly increased the expression levels of p62/SQSTM1, Beclin 1, and LC3II in Panc-1 cells. Punctate LC3II staining confirmed autophagy. Furthermore, inhibiting autophagy by chloroquine, 3-methyladenine, or LC3II siRNA significantly blocked parthenolide-induced apoptosis, suggesting that parthenolide induced apoptosis through autophagy in this study. In conclusion, these studies established that parthenolide inhibits pancreatic cell growth by autophagy-mediated apoptosis. Data of the present study suggest that parthenolide can serve as a potential chemotherapeutic agent for pancreatic cancer. PMID:28176967

  20. Suppression of atherosclerosis by synthetic REV-ERB agonist

    SciTech Connect

    Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  1. Prevalence and indicators of viral suppression among persons with diagnosed HIV infection retained in care - Georgia, 2010.

    PubMed

    Edison, Laura; Hughes, Denise; Drenzek, Cherie; Kelly, Jane

    2014-01-24

    Advances in treatment have led to dramatic improvements in the health of persons infected with human immunodeficiency virus (HIV). Moreover, treatment can reduce HIV transmission because suppressed levels of circulating virus makes HIV-infected persons less infectious. Until recently, antiretroviral therapy (ART) was recommended only for HIV patients with advanced disease (stages 2 and 3), and was optional for patients with early disease (stage 1). In March 2012, national HIV treatment guidelines were changed to recommend ART at all disease stages. To establish a baseline for care and treatment outcomes among persons with HIV, the Georgia Department of Public Health (DPH) examined whether viral suppression among HIV patients in Georgia varied by disease stage at diagnosis before implementation of the new guidelines. Disease stage at diagnosis was assessed as an indicator of viral suppression several months after diagnosis, adjusting for age, sex, and race/ethnicity among patients who were reported to DPH with HIV infections newly diagnosed during 2010 and retained in care. This report describes the results of that analysis, which indicated that disease stage at diagnosis was a significant indicator of viral suppression; viral suppression was significantly less frequent among persons with earlier disease stage at diagnosis. Compared with viral suppression among 80.5% of persons with stage 3 HIV disease, only 72.3% with stage 2 disease (prevalence ratio [PR] = 0.9; 95% confidence interval [CI] = 0.8-1.0) and 64.5% with stage 1 disease (PR = 0.8; CI = 0.7-0.9) met criteria for viral suppression, likely resulting from lack of initiating treatment or inadequate adherence to treatment regimens, as suggested in previous studies. These data can serve as a baseline to determine the impact of the guideline change in the future, and can be used to emphasize the importance of implementing the guidelines by expanding treatment to persons at all disease stages to reach the goal

  2. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.

    PubMed

    Trovero, Fabrice; David, Sabrina; Bernard, Philippe; Puech, Alain; Bizot, Jean-Charles; Tassin, Jean-Pol

    2016-01-01

    Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg) and cyproheptadine (1 mg/kg) (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively) blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v) and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France) and cyproheptadine (1 mg/kg) could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.

  3. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence

    PubMed Central

    Trovero, Fabrice; David, Sabrina; Bernard, Philippe; Puech, Alain; Bizot, Jean-Charles; Tassin, Jean-Pol

    2016-01-01

    Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg) and cyproheptadine (1 mg/kg) (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively) blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v) and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France) and cyproheptadine (1 mg/kg) could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs. PMID:26968030

  4. Unsuppressible Repetition Suppression and exemplar-specific Expectation Suppression in the Fusiform Face Area.

    PubMed

    Pajani, Auréliane; Kouider, Sid; Roux, Paul; de Gardelle, Vincent

    2017-12-01

    Recent work casts Repetition Suppression (RS), i.e. the reduced neural response to repeated stimuli, as the consequence of reduced surprise for repeated inputs. This research, along with other studies documenting Expectation Suppression, i.e. reduced responses to expected stimuli, emphasizes the role of expectations and predictive codes in perception. Here, we use fMRI to further characterize the nature of predictive signals in the human brain. Prior to scanning, participants were implicitly exposed to associations within face pairs. Critically, we found that this resulted in exemplar-specific Expectation Suppression in the fusiform face-sensitive area (FFA): individual faces that could be predicted from the associations elicited reduced FFA responses, as compared to unpredictable faces. Thus, predictive signals in the FFA are specific to face exemplars, and not only generic to the category of face stimuli. In addition, we show that under such circumstances, the occurrence of surprising repetitions did not trigger enhanced brain responses, as had been recently hypothesized, but still suppressed responses, suggesting that repetition suppression might be partly 'unsuppressible'. Repetition effects cannot be fully modulated by expectations, which supports the recent view that expectation and repetition effects rest on partially independent mechanisms. Altogether, our study sheds light on the nature of expectation signals along the perceptual system.

  5. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields.

    PubMed

    Todorovic, Ana; de Lange, Floris P

    2012-09-26

    Repetition of a stimulus, as well as valid expectation that a stimulus will occur, both attenuate the neural response to it. These effects, repetition suppression and expectation suppression, are typically confounded in paradigms in which the nonrepeated stimulus is also relatively rare (e.g., in oddball blocks of mismatch negativity paradigms, or in repetition suppression paradigms with multiple repetitions before an alternation). However, recent hierarchical models of sensory processing inspire the hypothesis that the two might be separable in time, with repetition suppression occurring earlier, as a consequence of local transition probabilities, and suppression by expectation occurring later, as a consequence of learnt statistical regularities. Here we test this hypothesis in an auditory experiment by orthogonally manipulating stimulus repetition and stimulus expectation and, using magnetoencephalography, measuring the neural response over time in human subjects. We found that stimulus repetition (but not stimulus expectation) attenuates the early auditory response (40-60 ms), while stimulus expectation (but not stimulus repetition) attenuates the subsequent, intermediate stage of auditory processing (100-200 ms). These findings are well in line with hierarchical predictive coding models, which posit sequential stages of prediction error resolution, contingent on the level at which the hypothesis is generated.

  6. Chronic activation of pattern recognition receptors suppresses brown adipogenesis of multipotent mesodermal stem cells and brown pre-adipocytes.

    PubMed

    Bae, Jiyoung; Chen, Jiangang; Zhao, Ling

    2015-06-01

    Brown adipose tissue (BAT) holds promise to combat obesity through energy-spending, non-shivering thermogenesis. Understanding of regulation of BAT development can lead to novel strategies to increase BAT mass and function for obesity treatment and prevention. Here, we report the effects of chronic activation of PRR on brown adipogenesis of multipotent mesodermal stem C3H10T1/2 cells and immortalized brown pre-adipocytes from the classical interscapular BAT of mice. Activation of NOD1, TLR4, or TLR2 by their respective synthetic ligand suppressed brown marker gene expression and lipid accumulation during differentiation of brown-like adipocytes of C3H10T1/2. Activation of the PRR only during the commitment was sufficient to suppress the differentiation. PRR activation suppressed PGC-1α mRNA, but induced PRDM16 mRNA at the commitment. Consistently, PRR activation suppressed the differentiation of immortalized brown pre-adipocytes. Activation of PRR induced NF-κB activation in both cells, which correlated with their abilities to suppress PPARγ transactivation, a critical event for brown adipogenesis. Taken together, our results demonstrate that chronic PRR activation suppressed brown adipogenesis of multipotent mesodermal stem cells and brown pre-adipocytes, possibly through suppression of PPARγ transactivation. The results suggest that anti- inflammatory therapies targeting PRRs may be beneficial for the BAT development.

  7. Suppression of pulmonary injury in experimental 'Goodpasture's syndrome' by deoxyspe