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  1. Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the lewis rat

    SciTech Connect

    Goldmuntz, E.A.; Brosnan, C.F.; Norton, W.T.

    1986-12-01

    Prazosin, an antagonist of the ..cap alpha../sub 1/-adrenoceptor, has been found to suppress the clinical and histologic expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. This effect appears to be specific for the ..cap alpha../sub 1/-receptor. To determine the effect of this drug on vascular permeability to serum proteins and inflammatory cells, leakage of serum proteins into the central nervous system (CNS) was measured with (/sup 125/I)albumin, and quantitation of cellular inflammation was determined by an estimation of total DNA. The results show that in both actively induced and passively transferred models of the disease, treatment with prazosin significantly suppresses leakage of serum proteins into the CNS but does not significantly suppress the increase of DNA. The results of the (/sup 125/I)albumin studies additionally support the conclusion that the extent of vascular permeability to serum proteins in the spinal cord is a significant correlate of clinical disease. The results of the DNA estimation were at variance with the histologic evidence of cellular infiltration. The authors conclude that treatment with prazosin has a significant effect on the development of vascular edema in EAE. These results additionally validate a role for the adrenergic receptor in the development of EAE, and support the hypothesis that the primary site of action of prazosin is on the vascular ..cap alpha../sub 1/-adrenoceptor.

  2. Prazosin

    MedlinePlus

    ... time taking prazosin, you should take it before you go to bed. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take prazosin exactly as directed. ...

  3. 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. PMID:25036580

  4. Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

    PubMed Central

    Brosnan, C F; Goldmuntz, E A; Cammer, W; Factor, S M; Bloom, B R; Norton, W T

    1985-01-01

    Prazosin, an antagonist of alpha 1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive effect of prazosin is a consequence of blockade of the alpha 1-receptor since treatment with either the alpha 2-antagonist yohimbine or the beta-antagonist propranolol exacerbated the disease, whereas treatment with the long-acting mixed alpha 1/alpha 2-antagonist phenoxybenzamine had some suppressive activity. Treatment with prazosin was also able to suppress clinical and histological signs of EAE in animals sensitized by adoptive transfer with activated spleen or lymph node cells. Whether prazosin acts through altering vascular permeability or the immune response, or both, remains to be determined. Images PMID:2994053

  5. 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

  6. Prazosin for the treatment of posttraumatic stress disorder sleep disturbances.

    PubMed

    Miller, Lisa J

    2008-05-01

    An estimated 70-87% of patients who suffer from posttraumatic stress disorder (PTSD) experience sleep disruption. These patients have distressing dreams or nightmares in which the traumatic event is reexperienced, and they also have difficulty in falling or staying asleep. Selective serotonin reuptake inhibitors are the treatment of choice for PTSD, but with the exception of fluvoxamine, they are often ineffective or only partially effective for sleep problems. Sedative-hypnotics may be helpful in the short term but are associated with tolerance and addiction potential. In the central nervous system, alpha(1)-adrenergic receptors are known to be important in both the startle and sleep responses. Stimulation of these receptors may contribute to PTSD-related trauma-content nightmares. Prazosin, a highly lipophilic alpha(1)-adrenergic receptor blocker that is traditionally used to treat hypertension and benign prostatic hyperplasia, has been shown to decrease the occurrence of trauma nightmares in both combat veterans and patients with non-combat-related PTSD. The available data, although mostly from open-label trials, suggest that this agent also improves sleep quality and patients' sense of wellbeing and ability to function in daily activities. The optimum dose is unknown; however, a dose-related response appears to be evident. Clinicians should monitor for orthostatic hypotension, usually seen early in therapy, when prazosin is started in patients with PTSD. PMID:18447662

  7. 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. PMID:19934720

  8. Effects of oral prazosin on total plasma digoxin levels.

    PubMed

    Copur, S; Tokgözoğlu, L; Oto, A; Oram, E; Uğurlu, S

    1988-01-01

    Prazosin and digoxin are frequently coadministered in clinical practice. To determine the effects of oral prazosin treatment on steady-state digoxin levels, 20 patients receiving a constant maintenance dose of digoxin, who had normal renal and liver functions and were not receiving any other treatment, were given 5 mg of prazosin for 3 days. Plasma digoxin levels were measured before, on days 1 and 3 of prazosin treatment, and after prazosin had been discontinued. It was found that prazosin significantly increased plasma digoxin levels. On discontinuation of prazosin digoxin levels returned to their previous values. PMID:3371837

  9. Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits

    PubMed Central

    Zubairi, Maysaa B.; Ahmed, Jawad H.; Al-Haroon, Sawsan S.

    2014-01-01

    Objectives: To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity. Materials and Methods: Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed. Results: Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments. Conclusion: Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection. PMID:25538338

  10. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use

    PubMed Central

    Skelly, Mary J; Weiner, Jeff L

    2014-01-01

    Background Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior. Methods Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period. Results Our results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P < 0.05). Furthermore, this decrease in drinking is accompanied by significant reductions in the expression of anxiety-like behavior (P < 0.05). Conclusions These findings suggest that chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a

  11. 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. PMID:26900667

  12. Prazosin

    MedlinePlus

    ... when not treated, can cause damage to the brain, heart, blood vessels, kidneys, and other parts of ... fast, pounding, or irregular heartbeat chest pain painful erection of the penis that lasts for hours

  13. 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

  14. 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. PMID:25429515

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

    PubMed

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

    2011-01-01

    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. PMID:24310595

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

    PubMed Central

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

    2014-01-01

    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 (0.01 mg/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 (1.0 mA, 0.5 s). 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. PMID:24246572

  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. PMID:26712326

  18. Responsiveness of superficial hand veins to phenylephrine in essential hypertension. Alpha adrenergic blockade during prazosin therapy.

    PubMed

    Eichler, H G; Ford, G A; Blaschke, T F; Swislocki, A; Hoffman, B B

    1989-01-01

    Patients with essential hypertension show an increase in vascular resistance. It is unclear whether this is caused by structural changes in the arterial wall or by hyperresponsiveness of vascular smooth muscle to endogenous alpha adrenergic agonists. Using the dorsal hand vein compliance technique we compared the changes in diameter of superficial veins in response to phenylephrine, an alpha 1 adrenergic receptor agonist, and to nitroglycerin, a venorelaxant, in patients with essential hypertension and in normotensive subjects. The dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) in the hypertensive subjects was 257 ng/min (geometric mean; log mean +/- SD was 2.41 +/- 0.54). In the control subjects the ED50 was 269 ng/min (geometric mean; log mean was 2.43 +/- 0.43). Maximal response (Emax) for phenylephrine was 84 +/- 13% in the hypertensive subjects and 90 +/- 6% in the control subjects. Differences in the group means of the ED50 (P = 0.92) or the Emax (P = 0.27) were not significant. There were no significant differences in the ED50 (P = 0.54) or the Emax (P = 0.08) for nitroglycerin between the two groups. These results show no evidence for a generalized change in alpha adrenergic responsiveness in hypertension and support the concept that increased blood pressure responses to alpha adrenergic stimulation in hypertensives are due to structural and geometric changes in the arterial wall rather than to an increased responsiveness of postsynaptic alpha adrenergic receptors. The phenylephrine studies were repeated in seven hypertensive patients during treatment with prazosin, an alpha 1 adrenergic antagonist. The mean dose ratio of the shift in phenylephrine ED50 (ED50 during prazosin therapy/ED50 before prazosin therapy) was 6.1. This indicates that small doses of prazosin (1-2 mg) cause significant in vivo shifts in the dose-response relationship of alpha adrenergic agonists. The dorsal hand vein compliance technique is useful in

  19. 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

  20. 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. PMID:25944011

  1. Thought suppression and treatment outcome in late-life depression.

    PubMed

    Rosenthal, M Z; Cheavens, J S; Compton, J S; Thorp, S R; Lynch, T R

    2005-01-01

    This study examined severity of depression, age of onset, and thought suppression as predictors of treatment outcome. Measures were taken pre-treatment, post-treatment, and at six-month follow-up in 34 depressed older adults receiving the treatment protocol described in Lynch, Morse, Mendelson & Robins (Dialectical behavior therapy for depressed older adults, American Journal of Geriatric Psychiatry, 11, 33-45, 2003). Severity and chronicity of depression and higher levels of thought suppression were associated with higher depressive symptoms six months after treatment. Findings are consistent with research suggesting that severity and chronicity of depression predict poor clinical outcome. In addition, these results provide preliminary evidence that the tendency to cope with unwanted thoughts by deliberate attempts to not experience such thoughts may be an important pre-treatment predictor of outcome among depressed older adults. Larger studies are needed to explore whether thought suppression mediates long-term recovery from depression. PMID:15841830

  2. Comparative bioavailability study of two brands of prazosin-containing tablets in healthy volunteers.

    PubMed

    Guelen, P J; Janssen, T J; Lam, M H; Vree, T B; Exler, P S

    1990-10-19

    The bioavailability of two prazosin formulations was studied in 12 healthy volunteers. 1 Subject left the study. Based on the statistical tests of the pharmacokinetic parameters of prazosin in 11 volunteers, such as t 1/2, Cmax, tmax and AUC, it could be concluded that both preparations had comparable bioavailabilities. PMID:2255586

  3. 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. PMID:17971903

  4. NON-NIGHTMARE DISTRESSED AWAKENINGS IN VETERANS WITH POSTTRAUMATIC STRESS DISORDER: RESPONSE TO PRAZOSIN

    PubMed Central

    Thompson, Charles E.; Taylor, Fletcher B.; McFall, Miles E.; Barnes, Robert F.; Raskind, Murray A.

    2011-01-01

    Twenty-two veterans with posttraumatic stress disorder (PTSD) were assessed for trauma-related nightmares (NM) and non-nightmare distressed awakenings (NNDA) before and after treatment with the alpha-1 adrenoreceptor antagonist prazosin at an average bedtime dose of 9.6 mg/day. Ratings combining frequency and intensity dimensions of NM decreased from 3.6 ± 2.6 to 2.2 ± 2.4 (p<0.05), NNDA from 5.2 ± 1.7 to 2.1 ± 2.4 (p<0.01), and sleep difficulty from 7.2 ± 8 to 4.1 ± 2.3 (p<0.01) per week. These results suggest that increased brain adrenergic activity may contribute to the pathophysiology of both NM and NNDA in PTSD. PMID:18720392

  5. Vasodilatation with captopril and prazosin in chronic heart failure: double blind study at rest and on exercise.

    PubMed

    Bayliss, J; Canepa-Anson, R; Norell, M S; Poole-Wilson, P; Sutton, G

    1986-03-01

    A double blind cross over study was performed to compare the long term hormonal, haemodynamic, and clinical responses to specific inhibition of the renin-angiotensin-aldosterone system (captopril) and of the alpha 1 adrenoceptors of the sympathetic system (prazosin) both at rest and during upright exercise in patients with chronic heart failure. Sixteen patients completed one month's treatment with each drug. During conventional diuretic treatment (control) plasma renin activity, aldosterone, and noradrenaline were increased at rest and on exercise. Control left ventricular filling pressures were raised, and correlated significantly with plasma renin activity both at rest and on exercise. Systemic vascular resistance was increased at rest, and its reduction during exercise correlated inversely with the increase in plasma renin activity and plasma noradrenaline. After one month's treatment with captopril there were reductions in plasma aldosterone, weight, left ventricular filling pressure, and systemic vascular resistance at rest and on exercise. Dyspnoea was relieved and exercise capacity increased. The greater fall in systemic vascular resistance on exercise no longer correlated with the increase in plasma renin activity. During treatment with prazosin there were increases in plasma noradrenaline and, transiently, in plasma aldosterone. Fluid retention occurred, and left ventricular filling pressure was unchanged. Compared with control values systemic vascular resistance was reduced at rest but not on exercise. Dyspnoea and exercise capacity did not improve. In chronic heart failure, vasodilatation by inhibition of the alpha adrenergic system with prazosin causes compensatory stimulation of the renin-angiotensin-aldosterone system and does not result in clinical benefit. Inhibition of the renin-angiotensin-aldosterone system with captopril causes secondary vasodilatation at rest and on exercise and results in improvement in symptoms and exercise capacity. PMID

  6. 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. PMID:18421626

  7. The Measurement and Treatment of Suppression in Amblyopia

    PubMed Central

    Black, Joanna M.; Hess, Robert F.; Cooperstock, Jeremy R.; To, Long; Thompson, Benjamin

    2012-01-01

    performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations. In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15. PMID:23271400

  8. Comparative effects of pinacidil and prazosin on blood pressure, weight, plasma volume, the renin-angiotensin-aldosterone system, and the renal kallikrein-kinin system in patients with essential hypertension.

    PubMed

    Solomon, R J; Weinberg, M S

    1987-12-01

    Patients with essential hypertension were randomized to treatment with either prazosin or pinacidil, a new direct-acting vasodilator. Factors that might modulate the antihypertensive response and result in pseudotolerance to these drugs were measured before initiation of therapy and following 12 weeks of treatment. Despite significant reductions in blood pressure, pinacidil and prazosin did not produce an increase in plasma volume, did not activate the renin-angiotensin-aldosterone system, and did not interfere with the renal kallikrein-kinin system. The data fail to reveal evidence of physiologic compensatory changes that would lead to the development of pseudotolerance. PMID:3330989

  9. Combined treatment with atorvastatin and minocycline suppresses severity of EAE.

    PubMed

    Luccarini, Ilaria; Ballerini, Clara; Biagioli, Tiziana; Biamonte, Filippo; Bellucci, Arianna; Rosi, Maria Cristina; Grossi, Cristina; Massacesi, Luca; Casamenti, Fiorella

    2008-05-01

    Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). An approach to improve MS treatment is to identify a rational combination of new medications or existing therapies that impact different aspects of the disease process. Statins are effective in the treatment of MS animal models and are promising candidates for future treatment. Minocycline ameliorates clinical severity of experimental autoimmune encephalomyelitis (EAE) and exhibits several anti-inflammatory and neuroprotective activities. In this study, we tested whether the combination of these two drugs could produce beneficial effects in EAE mice immunized with myelin oligodendrocyte protein (MOG). Our findings show that combined treatment, compared to using the medications alone, resulted in a significant reduction in disease severity, in both the acute and chronic phases of the disease, along with attenuation of inflammation, demyelination and axonal loss. Stereological analysis revealed that the combined treatment significantly guarded against neuroinflammation and neurodegeneration. Moreover, a significant suppression of anti-MOG antibody production in animals treated with the two medications was found. In conclusion, our findings prove that this combination of drugs is neuroprotective and suppresses the severity of EAE. Furthermore, this pharmacological approach appears to be promising as a future therapeutic strategy to control MS. PMID:18346732

  10. Advances in the Design and Synthesis of Prazosin Derivatives over the Last Ten Years

    PubMed Central

    Desiniotis, Andreas; Kyprianou, Natasha

    2012-01-01

    Introduction Mechanistic, translational and pharmacological studies led to the identification, preferred localization, binding characteristics, structure and functional properties of α1-adrenoceptor (α1-AR) subtypes in the bladder neck, bladder and prostate gland. The evidence gathered on α1-ARs, provided a molecular platform for the development of subtype selective antagonists, resulting in more effective approaches targeting those receptors for the treatment of outlet bladder obstruction and benign prostate hyperplasia. Areas Covered This review provides a comprehensive synopsis of advances over the last decade, in the design and optimization of Prazosin, Doxazosin, Terazosin quinazoline-based derivatives as clinically effective α1-AR antagonists. Furthermore, it discusses evidence on the metabolic and growth interference action by these agents, in addition to their smooth-muscle relaxing effects. The new action recognition emerges from compelling data on the inhibitory effect of quinazoline-based antagonists on primary tumor growth and progression to metastasis. In addition to the cellular findings in the prostate, functional validation and therapeutic impact of selected lead pharmaceutically optimized derivatives in the context of impairing vascularity and triggering tumor apoptosis, are also summarized. Expert Opinion The expanding knowledge on targeting intracellular signalling pathways driving the cellular response via an α1-AR dependent and independent antagonistic action, must be invested towards the optimization of new agents that while bypassing AR, exhibit improved pharmacological efficacy against human cancer. PMID:22148952

  11. The potential for prazosin and calcitonin gene-related peptide (CGRP) in causing hypoxia in tumours.

    PubMed Central

    Burney, I. A.; Maxwell, R. J.; Griffiths, J. R.; Field, S. B.

    1991-01-01

    Using 31P NMR spectroscopy, changes in tumour metabolic status were studied in a transplanted rat fibrosarcoma following the administration of vasodilators. Mean Arterial Blood Pressure (MABP) was monitored simultaneously. Two vasodilators were studied, prazosin and CGRP, which altered the NMR parameters Pi/sigma P, beta NTP,Pi, PCr/Pi and PME/Pi in a dose dependent manner. There was a good correlation between the various NMR parameters; for analysis, Pi/sigma P was used for convenience. With increasing doses of vasodilator, Pi/sigma P increased and the MABP decreased. Reduction in pHNMR showed a correlation with decreasing MABP following the administration of prazosin but not after CGRP. Both prazosin and CGRP produced changes in 31P NMR spectra consistent with a reduction in tumour blood flow. The results for prazosin and CGRP were comparable and showed a 15-20% increase in Pi/sigma P for a 20% reduction in MABP. These results were compared with those from hydralazine. With hydralazine an acceptable reduction in blood pressure (up to approximately 25%) has little effect and may even alter NMR parameters consistent with an increase in blood flow, a reduction of approximately 40% is required for a significant decrease in flow. Both prazosin and CGRP are shown to be far more effective than hydralazine in causing tumour hypoxia at a clinically acceptable reduction in blood pressure. CGRP may be the more suitable for clinical use because of its short half life, its capability to achieve controlled hypotension and the relatively few side effects associated with its use. PMID:1911217

  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. PMID:24107430

  13. Lack of specific (/sup 3/H) prazosin binding sites in dog and rabbit cerebral arteries

    SciTech Connect

    Ferron, P.M.; Banner, W. Jr.; Duckles, S.P.

    1984-11-19

    In order to explore the characteristics of alpha adrenergic receptors on cerebrovascular smooth muscle, specific binding sites for the alpha/sub 1/ adrenergic ligand, (/sup 3/H) prazosin, were studied in blood vessel homogenates. No specific (/sup 3/H) prazosin binding was found in either rabbit or dog cerebral arteries, but specific binding was demonstrated in the rabbit saphenous and ear arteries. In the ear artery /sup 3/H-prazosin binding was saturable with a K/sub d/ of 0.51 +/- 0.20 nM and a Bmax of 89 +/- 29 fmoles/mg protein. To confirm the adequacy of our membrane preparation, homogenates of both dog and rabbit cerebral arteries showed saturable specific binding with two different ligands: one for muscarinic receptors, (/sup 3/H)(-) quinuclidinyl benzilate (QNB) and one for alpha/sub 2/ adrenergic receptors, (/sup 3/H) yohimbine. The results of these studies demonstrate a lack of alpha/sub 1/ adrenergic receptors on cerebral blood vessels, confirming functional studies showing only a weak contractile response to norepinephrine. 29 references, 3 figures, 2 tables.

  14. 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.

  15. Treatment of pastures with diflubenzuron suppresses Horn Fly, Haematobia irritans (L.) (Diptera: Muscidae) development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diflubenzuron is an insect growth regulator labeled for application to pastures and rangeland to suppress grasshopper (Orthoptera: Acrididae) populations. Livestock are permitted access to land immediately after treatment. We hypothesized that the development and survivorship of horn fly Haematobia ...

  16. 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. PMID:25356000

  17. 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

  18. A Pilot Trial of Prazosin, an Alpha-1 Adrenergic Antagonist, for Comorbid Alcohol Dependence and Posttraumatic Stress Disorder

    PubMed Central

    Simpson, Tracy L.; Malte, Carol A.; Dietel, Bergetta; Tell, Dana; Pocock, Ian; Lyons, Robert; Varon, Dana; Raskind, Murray; Saxon, Andrew J.

    2015-01-01

    Background Posttraumatic Stress Disorder (PTSD) and alcohol dependence (AD) commonly co-occur and are associated with greater symptom severity and costs than either disorder alone. No pharmacologic interventions have been found to decrease both alcohol use and PTSD symptom severity relative to matched placebo. Prazosin, an alpha-1 adrenoreceptor antagonist, has demonstrated efficacy reducing PTSD and AD symptoms among individuals with one or the other disorder and may be useful in addressing comorbid PTSD/AD. Methods Prazosin and matched placebo were compared in the context of an outpatient 6-week double-blind randomized controlled pilot trial involving 30 individuals with comorbid PTSD/AD. Medication was titrated to 4mg q AM, 4mg q PM and 8mg qhs by the end of week 2. Participants in both conditions received five Medical Management sessions. Information regarding alcohol use, craving, and PTSD was gathered daily using a telephone Interactive Voice Response (IVR) system. Results Participants randomized to prazosin had a greater reduction in percent days drinking per week and percent days heavy drinking per week between baseline and week 6 than did placebo participants. No significant differences were detected within or between groups in change from weeks 1 to 6 in total PTSD symptoms. Participants in the prazosin condition reported drowsiness on significantly more days than those in the placebo condition. Conclusions Consistent with the extant research evaluating medications for comorbid PTSD/AD, the current evaluation of prazosin also found decreased alcohol consumption but no medication effect on PTSD symptomatology. PMID:25827659

  19. Suppressed or enhanced antibody responses in vitro after BCG treatment of mice: importance of BCG viability.

    PubMed Central

    Brown, C A; Brown, I N; Sljivić, V S

    1979-01-01

    Mycobacterium bovis, BCG, is known to be capable of either enhancing or suppressing various immune responses. Using a standard technique and number of organisms, some of the parameters predetermining whether enhancement or supression will occur have been investigated. Dead BCG given intravenously into mice caused an enhancement of the antibody response in vitro to sheep erythrocytes. In contrast, the same number of viable organisms caused suppression if given intravenously but enhancement if given subcutaneously. The inclusion of 25% or more killed organisms in an intravenous inoculum of fully viable organisms changed suppression to enhancement. Treatment of BCG infected mice with streptomycin lessened the suppression but did not change it to enhancement. The possible causes of suppression are discussed. PMID:391696

  20. Development and evaluation of treatment paradigms for the suppression of smoking behavior.

    PubMed Central

    Dericco, D A; Brigham, T A; Garlington, W K

    1977-01-01

    A multiple-baseline component-analysis design was employed to assess the effectiveness of three treatment programs for suppressing the cigarette smoking behavior of 24 subjects. Sartiation, cognitive control, and continger shock procedures were evaluated. The results demonstrated a consistent relationship between contingent shock and suppression of smoking. It was further indicated that subjects should be exposed to the number of sessions necessary to achieve total suppression in order to gain maximally from treatment and to avoid relapse. Neither the satiation component nor the cognitive control component was correlated with clear, permanent decrements in smoking frequencies. To date no other treatment program has demonstrated the dramatic effects ofethe contingent shock procedures used in the present study. PMID:885824

  1. Surface treatment method for 1/f noise suppression in reactively sputtered nickel oxide film

    NASA Astrophysics Data System (ADS)

    Kim, Dong Soo; Park, Seung-Man; Lee, Hee Chul

    2012-07-01

    A surface treatment method combined with O2 plasma treatment and Ar+ bombardment is proposed for 1/f noise suppression in a reactively sputtered NiO film as a micro-bolometer sensing material. The 1/f noise power spectral density on a sample prepared by the proposed surface treatment method prior to the contact formation is suppressed to a level roughly 18 times lower than that on an untreated sample. The improved noise characteristic can be ascribed to the cooperative effects of the two steps in the proposed surface treatment method. In its effects, the oxygen plasma treatment is supposed to increase the Ni3+ component on the surface of the NiO film, which in turn increases the hole concentration on the surface. Additional Ar+ bombardment is expected to remove contaminants on the surface of the NiO film, leading to a low contact resistance.

  2. The α1 Adrenergic Receptor Antagonist Prazosin Reduces Heroin Self-Administration in Rats with Extended Access to Heroin Administration

    PubMed Central

    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 in dependent rats. Prazosin, an α1-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). The data show that the α1-adrenergic system may contribute to mechanisms that promote dependence in rats with extended drug access, while also stimulating their food intake by restoring meals to the normal size and duration. PMID:18703080

  3. 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.

  4. The effect of prazosin pretreatment on hyperthermia produced by noradrenaline in rabbits.

    PubMed

    Szreder, Z

    1991-01-01

    1. Hyperthermia produced by noradrenaline (NA) was accompanied by increased metabolic rate and vasoconstriction of ear skin vessels and a fall in evaporation heat loss. 2. Prazosin (PRA), administered as a single injection, decreased of hyperthermia elicited by NA mainly of attenuation the processes concerned with the heat production and increased of heat loss from respiratory tract and ear skin surface. 3. PRA administered in a 3 hr infusion did not only produce an abolishment of NA-induced hyperthermia but also exerted a hypothermizing effect. 4. PRA introduced intracerebroventricularly also induced a decline in core temperature, inhibiting the metabolic rate stimulated by this amine. 5. These results seem to suggest that NA-caused hyperthermia may be controlled through central adrenergic structures, which are effectively blocked by PRA. Besides, we have presented one more proof concerning the antihyperthermizing activity of PRA and its central point of activity catch. PMID:1869019

  5. Emotional suppression tendencies as predictors of symptoms, mood, and coping appraisals during AC chemotherapy for breast cancer treatment.

    PubMed

    Schlatter, Melanie C; Cameron, Linda D

    2010-08-01

    Tendencies to suppress negative emotions have been shown to predict adjustment to cancer and cancer progression. We examined whether emotional suppression, in terms of both general and emotion-specific tendencies, predict symptom reports, mood states, and coping appraisals during adriamycin/doxorubicin, cyclophosphamide/cytoxan chemotherapy for breast cancer. Forty participants completed a measure yielding scores for anxiety suppression, anger suppression, depression suppression, and total emotional suppression. They then reported their experiences of 34 physical symptoms, mood, and coping efficacy on a daily basis for the duration of treatment (84 days). Mixed model analyses revealed that emotional suppression predicted lower reports of symptoms that are vague, well-known, and potentially embarrassing side effects of chemotherapy (e.g., fatigue and constipation). Emotional suppression and particularly anger suppression predicted higher reports of symptoms relating to immune function and cardiovascular arousal (e.g., mouth sores and heart palpitations) and with appraisals of poorer coping. The three suppression tendencies exhibited distinctive patterns of relationships with symptoms, mood, and coping appraisals, suggesting that anxiety suppression, anger suppression, and depression suppression have partially independent relationships with symptomatic and mood processes. The findings highlight the potential importance of emotional suppression for understanding symptom and coping responses during chemotherapy. PMID:20652465

  6. Comparative study on pharmacokinetics and in vivo alpha1-adrenoceptor binding of [3H]tamsulosin and [3H]prazosin in rats.

    PubMed

    Ohkura, T; Yamada, S; Deguchi, Y; Kimura, R

    1999-04-01

    The plasma concentration, total radioactivity and in vivo alpha1-adrenoceptor binding in rat tissues after intravenous (i.v.) injection of [3H]tamsulosin were measured and they were compared with those obtained after the injection of [3H]prazosin. The plasma concentration of [3H]tamsulosin was consistently higher than that of [3H]prazosin, with 1.4 times greater areas under the curve (AUC(0-infinity)) of plasma concentration. As there was a significantly lower value of apparent volume of central compartment (Vd(c)) and distribution volume at steady state (Vd(ss)) for [3H]tamsulosin than [3H]prazosin with little difference in elimination rate constant (beta), the higher concentration of [3H]tamsulosin in plasma might be associated mainly with the smaller volume of distribution. The ratio of total radioactivity in tissues to the plasma unbound concentration of [3H]tamsulosin after i.v. injection of the ligand was consistently lower than that of [3H]prazosin. These observations suggest that [3H]tamsulosin is distributed in rat tissues in a more limited manner than [3H]prazosin. A significantly lower level of in vivo specific binding of [3H]tamsulosin than [3H]prazosin was observed in the spleen, heart and liver. Further, the apparent dissociation constant (Kd) and maximal number of binding sites (Bmax) for in vivo specific [3H]tamsulosin binding were considerably lower than those for [3H]prazosin binding. Therefore, these findings suggest that [3H]tamsulosin labels preferentially a subpopulation of the alpha1-adrenoceptor sites in rat tissues labeled by [3H]prazosin. In conclusion, the present study has shown that there is a significant difference in the pharmacokinetics and in vivo alpha1-adrenoceptor binding characteristics between tamsulosin and prazosin. PMID:10328564

  7. Food Thought Suppression Inventory: Test-retest reliability and relationship to weight loss treatment outcomes.

    PubMed

    Barnes, Rachel D; Ivezaj, Valentina; Grilo, Carlos M

    2016-08-01

    This study examined the test-retest reliability of the Food Thought Suppression Inventory (FTSI) and its relationship with weight loss during weight loss treatment. Participants were 89 adults with and without binge eating disorder (BED) recruited through primary care for weight loss treatment who completed the FTSI twice prior to starting treatment. Intra-class correlations for the FTSI ranged from .74-.93. Participants with BED scored significantly higher on the FTSI than those without BED at baseline only. Percent weight loss from baseline to mid-treatment was significantly negatively correlated with the FTSI at baseline and at post-treatment. Participants reaching 5% loss of original body weight by post-treatment had significantly lower FTSI scores at post assessment when compared to those who did not reach this weight loss goal. While baseline binge-eating episodes were significantly positively correlated with baseline FTSI scores, change in binge-eating episodes during treatment were not significantly related to FTSI scores. The FTSI showed satisfactory one week test-retest reliability. Higher levels of food thought suppression may impair individuals' ability to lose weight while receiving weight loss treatment. PMID:27112114

  8. 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.

  9. 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. PMID:25447534

  10. 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

  11. 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. PMID:10606626

  12. 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.

  13. 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

  14. Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women

    PubMed Central

    Topyildiz, Figen; Kiyici, Sinem; Gul, Zulfiye; Sigirli, Deniz; Guclu, Metin; Kisakol, Gurcan; Cavun, Sinan

    2016-01-01

    Aim. To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus. Methods. Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated. Results. Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4 ± 57.5 versus 234.5 ± 59.4 pg/mL) (p < 0.001). Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p = 0.001). Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p = 0.035). Conclusion. These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide. PMID:26998491

  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

    2015-12-01

    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. 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.

  17. Acthar gel treatment suppresses acute exacerbations in a murine model of relapsing-remitting multiple sclerosis.

    PubMed

    Cusick, Matthew F; Libbey, Jane E; Oh, Luke; Jordan, Shaun; Fujinami, Robert S

    2015-06-01

    Acthar gel is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Its effects on immune cells during a relapse are unknown. This study investigated the effects of Acthar in an animal model of relapsing-remitting MS, using SJL/J mice sensitized with myelin peptide. All animal studies were reviewed and approved by the University of Utah Institutional Animal Care and Use Committee and conducted in accordance with the guidelines prepared by the Committee on Care and Use of Laboratory Animals, Institute of Laboratory Animals Resources, National Research Council. Mice injected with Acthar to treat the second attack had a significantly lower mean clinical score during relapse and a significantly reduced cumulative disease burden compared to Placebo gel-treated mice. Furthermore, Acthar treatment ameliorated inflammation/demyelination in the spinal cord and markedly suppressed ex vivo myelin peptide-induced CD4(+) T cell proliferation. PMID:25410153

  18. 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. PMID:25970279

  19. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment

    PubMed Central

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D.; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-01-01

    Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI). Design: Longitudinal observational study. Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4+ cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+ cell count, differences in CD4+ cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI. PMID:26636925

  20. Viral suppression in adolescents on antiretroviral treatment: A review of the literature and critical appraisal of methodological challenges

    PubMed Central

    Ferrand, Rashida A; Briggs, Datonye; Ferguson, Jane; Penazzato, Martina; Armstrong, Alice; MacPherson, Peter; Ross, David A; Kranzer, Katharina

    2016-01-01

    Background Medication adherence is often sub-optimal for adolescents with HIV, and establishing correct weight-based antiretroviral therapy dosing is difficult, contributing to virological failure. This review aimed to determine the proportion of adolescents achieving virological suppression after initiating ART. Methods MEDLINE, EMBASE and Web of Science databases were searched. Studies published between January 2004 and September 2014 including ≥ 50 adolescents taking ART and reporting on the proportion of virological suppressed participants were included. Results From a total of 5316 potentially relevant citations, 20 studies were included. Only 8 studies reported the proportion of adolescents that were virologically suppressed at a specified time point. The proportion of adolescents with virological suppression at 12 months ranged from 27%-89%. Conclusion Adolescent achievement of HIV virological suppression was highly variable. Improved reporting of virological outcomes from a wider range of settings is required to support efforts to improve HIV care and treatment for adolescents. PMID:26681359

  1. The relation of weight suppression and body mass index to symptomatology and treatment response in anorexia nervosa.

    PubMed

    Berner, Laura A; Shaw, Jena A; Witt, Ashley A; Lowe, Michael R

    2013-08-01

    Weight suppression, the difference between highest past weight and current weight, is a robust predictor of clinical characteristics of bulimia nervosa; however, the influence of weight suppression in anorexia nervosa (AN) has been little studied, and to our knowledge, no study to date has investigated the ways in which the relevance of weight suppression in AN may depend upon an individual's current body mass index (BMI). The present study investigated weight suppression, BMI, and their interaction as cross-sectional and prospective predictors of psychological symptoms and weight in AN. Women with AN completed depression (Beck Depression Inventory-II) and eating disorder symptomatology measures (Eating Disorder Examination Questionnaire and Eating Disorders Inventory-3) at residential treatment admission (N = 350) and discharge (N = 238). Weight suppression and BMI were weakly correlated (r = -.22). At admission, BMI was positively correlated with all symptom measures except Restraint and Depression scores. Weight suppression was also independently positively correlated with all measures except Weight Concern and Body Dissatisfaction subscale scores. In analyses examining discharge scores (including admission values as covariates), the admission weight suppression × BMI interaction consistently predicted posttreatment psychopathology. Controlling for weight gain in treatment and age, higher admission weight suppression predicted lower discharge scores (less symptom endorsement) among those with lower BMIs; among those with higher BMIs, higher weight suppression predicted higher discharge scores. These results are the first to our knowledge to demonstrate that absolute and relative weight status are joint indicators of AN severity and prognosis. These findings may have major implications for conceptualization and treatment of AN. PMID:24016010

  2. Suppression of bovine lymphocyte responses to mitogens following in vivo and in vitro treatment with dexamethasone.

    PubMed

    Oldham, G; Howard, C J

    1992-01-15

    Gnotobiotic calves given intramuscular injections of dexamethasone (DM, 0.5 mg kg-1 day-1) showed marked changes in haematological parameters including a neutrophilia and a lymphopaenia. Not only was there a reduction in the numbers of circulating mononuclear cells, but there was also a significant (P less than 0.01) decrease in the in vitro responsiveness of the remaining circulating peripheral blood lymphocytes to the mitogens, phytohaemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM). Responses to all three mitogens were suppressed to a similar degree. Analysis of the circulating mononuclear cell sub-populations before and during DM treatment demonstrated a selective depletion of B cells; the T lymphocyte sub-population that expresses the gamma/delta form of T cell receptor, are CD2-, CD5+, CD8-, CD4- and constitute a major population in peripheral blood of calves. In vitro studies in gnotobiotic and conventional calves confirmed that DM was highly inhibitory for PHA responses but, in contrast to the in vivo findings, showed little effect of DM on ConA responses. Expression of surface antigens after 72 h in vitro culture in the presence of DM were little affected with the exception of BoCD8 and MHC II, which showed increased and decreased expression, respectively. These observations would suggest that distinct mechanisms are involved in glucocorticosteroid suppression of the responses to these two mitogens. PMID:1534431

  3. Chronic treatment with anti-bipolar drugs suppresses glutamate release from astroglial cultures.

    PubMed

    Liu, Zhuo; Song, Dan; Yan, Enzhi; Verkhratsky, Alexei; Peng, Liang

    2015-05-01

    Astroglial cells are fundamental elements of most neurological diseases, including bipolar disorders in which astrocytes show morphological and functional deficiency. Here we report the suppression of astroglial glutamate release by chronic treatment with three anti-bipolar drugs, lithium salt (Li(+)), carbamazepine (CBZ) and valproic acid (VPA). Release of glutamate was triggered by transient exposure of astrocytes to ATP (which activated purinoceptors) and 45 mM K(+) (which depolarised cell membrane to ~-30 mV). In both types of stimulation glutamate release was regulated by Ca(2+) entry through plasmalemmal channels and by Ca(2+) release from the endoplasmic reticulum (ER) intracellular stores. Exposure of astroglial cultures to Li(+), CBZ and VPA for 2 weeks led to a significant (more than 2 times) inhibition of glutamate release, which may alleviate the hyperactivity of the glutamatergic transmission in the brain of patients with bipolar disorders and thus contribute the underlying mechanism of drug action. PMID:25676933

  4. 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.

  5. 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. PMID:15938591

  6. 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. PMID:27396658

  7. Alpha-adrenoceptors in dog mesenteric vessels--subcellular distribution and number of ( sup 3 H)prazosin and ( sup 3 H)rauwolscine binding sites

    SciTech Connect

    Shi, A.G.; Ahmad, S.; Kwan, C.Y.; Daniel, E.E. )

    1990-04-01

    Binding of the alpha-adrenergic antagonists ({sup 3}H)prazosin and ({sup 3}H)rauwolscine to well-characterized subcellular membrane fractions isolated from dog mesenteric arteries and veins was studied. Binding of both ligands was saturable with Kd values of 0.5 +/- 0.1 nM for ({sup 3}H)prazosin and 5.85 +/- 0.85 nM for ({sup 3}H)rauwolscine in arteries, and 0.87 +/- 0.4 nM for ({sup 3}H)prazosin and 6.6 +/- 1.5 nM for ({sup 3}H)rauwolscine in veins. In veins, the maximum number of binding sites for ({sup 3}H)rauwolscine was higher than that for ({sup 3}H)prazosin, whereas in arteries the maximum number of binding sites for each ligand was similar. In microsomes from dog aorta, the maximum number of bindings sites for ({sup 3}H)prazosin was higher than that for ({sup 3}H)rauwolscine. Neuronal membrane contamination in these studies was minimized by dissection procedures and evaluated by the comparison of ({sup 3}H)saxitoxin binding in various preparations. Only mesenteric veins responded functionally to agonists acting on alpha 2 adrenoceptors. This study thus identified two distinct populations of ({sup 3}H)prazosin and ({sup 3}H)rauwolscine binding sites in the plasma membranes of dog mesenteric vessels and suggests that a much higher density of alpha 2-compared to alpha 1-adrenoceptor binding sites is required for a contractile response.

  8. 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.

  9. 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. PMID:24211380

  10. 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)

  11. 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. PMID:27338952

  12. MTDH is an oncogene in multiple myeloma, which is suppressed by Bortezomib treatment

    PubMed Central

    Yang, Hongbao; Feng, Zhenqing; Yang, Ye

    2016-01-01

    Metadherin (MTDH) is identified as an oncogene in multiple cancers including breast cancer, bladder cancer and endometrial cancer. However, the function of MTDH in multiple myeloma (MM) is still unexplored. In this study, we disclose that MTDH is an oncogene in MM. This is characterized by an elevation mRNA level of MTDH and chromosomal gain of MTDH locus in MM cells compared to normal samples. Moreover, MTDH expression significantly increased in MMSET translocation (MS) subgroup, one of the high-risk subgroups in MM, and was significantly correlated with MM patients' poor outcomes in Total Therapy 2 (TT2) cohort. Further knockdown of MTDH expression by shRNA in MM cells induced cell apoptosis, inhibited MM cells growth in vitro and decreased xenograft tumor formation in vivo. Interestingly, opposite to TT2, MM patients with high-MTDH expression showed favorable survival outcomes in the TT3 cohort, while Bortezomib treatment was the major difference between TT2 and TT3 cohort. Furthermore we proved that Bortezomib suppressed pre- and post-transcription levels of MTDH expression of MM cells in vitro and in vivo. Finally, our studies demonstrated that MTDH is a transcriptional gene of MMSET/NFκB /MYC signaling in MM cells, which is inhibited by Bortezomib treatment. PMID:26683226

  13. Chronic retinoic acid treatment suppresses adult hippocampal neurogenesis, in close correlation with depressive-like behavior.

    PubMed

    Hu, Pu; Wang, Yu; Liu, Ji; Meng, Fan-Tao; Qi, Xin-Rui; Chen, Lin; van Dam, Anne-Marie; Joëls, Marian; Lucassen, Paul J; Zhou, Jiang-Ning

    2016-07-01

    Clinical studies have highlighted an association between retinoid treatment and depressive symptoms. As we had shown before that chronic application of all-trans retinoic acid (RA) potently activated the hypothalamus-pituitary-adrenal (HPA) stress axis, we here questioned whether RA also induced changes in adult hippocampal neurogenesis, a form of structural plasticity sensitive to stress and implicated in aspects of depression and hippocampal function. RA was applied intracerebroventricularly (i.c.v.) to adult rats for 19 days after which animals were subjected to tests for depressive-like behavior (sucrose preference) and spatial learning and memory (water maze) performance. On day 27, adult hippocampal neurogenesis and astrogliosis was quantified using BrdU (newborn cell survival), PCNA (proliferation), doublecortin (DCX; neuronal differentiation), and GFAP (astrocytes) as markers. RA was found to increase retinoic acid receptor-α (RAR-α) protein expression in the hippocampus, suggesting an activation of RA-induced signaling mechanisms. RA further potently suppressed cell proliferation, newborn cell survival as well as neurogenesis, but not astrogliosis. These structural plasticity changes were significantly correlated with scores for anhedonia, a core symptom of depression, but not with water maze performance. Our results suggest that RA-induced impairments in hippocampal neurogenesis correlate with depression-like symptoms but not with spatial learning and memory in this design. Thus, manipulations aimed to enhance neurogenesis may help ameliorate emotional aspects of RA-associated mood disorders. © 2016 Wiley Periodicals, Inc. PMID:26860546

  14. Urea cycle gene expression is suppressed by PFOA treatment in rats.

    PubMed

    Walters, M W; Wallace, K B

    2010-08-01

    Perfluorooctanoic acid (PFOA), with an array of industrial uses, is one of the most common perfluoroalkyl acids. Resistance to biological degradation and a global distribution are characteristics that have caused PFOA to become a frequent subject of toxicological studies. PFOA treatment in rodents causes peroxisome proliferation, mitochondrial biogenesis, and transactivation of PPARs. Prior work has shown urea cycle gene expression to be reduced in mice by another PPARalpha ligand, WY14643. In light of these findings, the aim of our investigation was to determine if PFOA treatment in rats alters expression of genes responsible for ureogenesis. 30 mg/kg of PFOA was administered to adult male Sprague-Dawley rats via oral gavage for 28 days and their livers were harvested. Gene transcription was measured using real time PCR and protein expression was determined through western blotting. We observed a decrease in mRNA for the coordinately expressed urea cycle genes Cps1, Ass1, and Asl; mRNA of the ammonia generating Gls2 was also reduced. Protein amounts for CPS1, ASS1, and OTC were all decreased in the PFOA treated rats, and interestingly there was an increase in the amount of S133 phosphorylated CREB, which is a regulator of urea cycle gene transcription. We conclude that the transactivation of PPARalpha by PFOA leads to a metabolic shift that favors the catabolism of lipids over proteins, thereby suppressing urea cycle gene expression. Our findings provide further evidence of the effect of PFOA on intermediary metabolism in rodents and add valuable information in assessing the potential risks of PFOA exposure. PMID:20452409

  15. Allosteric interactions between the antagonist prazosin and amiloride analogs at the human alpha(1A)-adrenergic receptor.

    PubMed

    Leppik, R A; Mynett, A; Lazareno, S; Birdsall, N J

    2000-03-01

    It has been demonstrated previously that amilorides can interact with a well defined allosteric site on the human alpha(2A)-adrenergic receptor. In this study, the question was explored as to whether the human alpha(1A)-adrenergic receptor also possesses an equivalent allosteric site. The six amilorides examined strongly increased the dissociation rate of the antagonist [(3)H]prazosin from the alpha(1A)-adrenergic receptor in a concentration-dependent manner. With the parent amiloride, the dissociation data were well fitted by an equation derived from the ternary complex allosteric model, compatible with amiloride acting at a defined allosteric site on the alpha(1A)-adrenergic receptor. In contrast, the dissociation data for [(3)H]prazosin in the presence of the amiloride analogs were not compatible with the equation derived from a one-allosteric-site model, but could be fitted well by an equation derived from a two-allosteric-site model. However, certain individual parameters could not be resolved. The observed dissociation rate constants increased steeply with increasing amiloride analog concentration, and in some cases the data could be fitted with a logistic equation. The slope factors calculated from such fits were 1.2 to 2.1. It is concluded that the structure-binding relationships of the amilorides at the alpha(1A)- and alpha(2A)-adrenergic receptors are different. The interactions of the five amiloride analogs, but not the parent amiloride, with the alpha(1A)-adrenergic receptor are compatible with the presence of two (but not one) allosteric sites, and is thus more complex than that found for the alpha(2A)-adrenergic receptor. PMID:10692482

  16. 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

  17. 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. PMID:20872142

  18. 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.

    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.

  19. 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.

  20. The advantages of subtotal thyroidectomy and suppression of TSH in the primary treatment of papillary carcinoma of the thyroid

    SciTech Connect

    Crile, G. Jr.; Antunez, A.R.; Esselstyn, C.B. Jr.; Hawk, W.A.; Skillern, P.G.

    1985-06-01

    Patients between the ages of 6 and 45 years with distant metastases from papillary carcinoma of the thyroid can be treated as effectively by subtotal thyroidectomy and suppressive doses of thyroid hormone as by total thyroidectomy followed by treatment with iodine 131 (/sup 131/I). Moreover, distant metastases can be treated by either /sup 131/I or suppression as effectively after they are apparent on x-ray as they can be when treated in a subclinical stage. Therefore, in patients younger than 45 years old it is rarely necessary to perform a total thyroidectomy or to do frequent postoperative scans. In patients older than 44 or younger than 7 who have distant metastases or extensive involvement of both lobes, total or almost total thyroidectomy is justified if it can be done with minimal morbidity. In patients of this age group whose tumors fail to respond to suppressive doses of thyroid, /sup 131/I should be used. In view of the importance of diagnostic related groups (DRG) to the economy of hospitals, we note that the cost of total thyroidectomy, ablation by /sup 131/I, and intermittent body scans is at least three times that of less radical procedures which, in conjunction with suppression by thyroid feeding, give the same survival with less morbidity.

  1. Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation

    PubMed Central

    Coe, Lindsay M.; Tekalur, Srinivasan Arjun; Shu, Yutian; Baumann, Melissa J.; McCabe, Laura R.

    2016-01-01

    Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Previous studies demonstrate that T1-diabetes decreases osteoblast activity and viability. Bisphosphonate therapy, commonly used to treat osteoporosis, is demonstrated to inhibit osteoclast activity as well as osteoblast apoptosis. Therefore, we examined the effect of weekly alendronate treatments on T1-diabetes induced osteoblast apoptosis and bone loss. Bone TUNEL assays identified that alendronate therapy prevents the diabetes-induced osteoblast death observed during early stages of diabetes development. Consistent with this, alendronate treatment for 40 days was able to prevent diabetes-induced trabecular bone loss. Alendronate was also able to reduce marrow adiposity in both control diabetic mice compared to untreated mice. Mechanical testing indicated that 40 days of alendronate treatment increased bone stiffness but decreased the work required for fracture in T1-diabetic and alendronate treated mice. Of concern at this later time point, bone formation rate and osteoblast markers, which were already decreased in diabetic mice, were further suppressed in alendronate treated diabetic mice. Taken together, our results suggest that short term alendronate treatment can prevent T1-diabetes-induced bone loss in mice, possibly in part by inhibiting diabetes onset associated osteoblast death, while longer treatment enhanced bone density but at the cost of further suppressing bone formation in diabetic mice. PMID:25641511

  2. Effect of concanavalin A treatment on the allogeneic response of mice to challenge with P 815 mastocytoma: interleukin 2 treatment reverses concanavalin A suppression in vivo.

    PubMed

    Ekstedt, R D; Merdian, D J

    1984-05-01

    Mice injected repeatedly with concanavalin A (Con A) prior to and following challenge with P 815 mastocytoma are suppressed in their cell-mediated cytotoxicity responses. Earlier studies showed that pretreatment of the animals with silica to affect macrophage (M phi) functions reversed the Con A suppression. In the present paper we have shown that peritoneal exudate cells (PEC) induced/activated by ip injection of Con A were able to transfer suppression to normal mice. Separation of the PEC populations into adherent and nonadherent cells abrogated their capacity to transfer suppression. It was further shown that Con A is not functioning in this in vivo system to block effector activity of cytotoxic cells on target cells, and PEC induced with Con A were not directly cytotoxic to target P 815 cells. Finally, we were able to show that the cytotoxicity response of Con A-suppressed mice could be enhanced by treatment with concentrated culture supernatants of normal mouse spleen cells, rich in interleukin 2 (IL 2) activity. Attempts to detect a recently described mouse serum inhibitor of IL 2 in normal or Con A-treated mice were unsuccessful and spleen cells from Con A-treated mice lost their capacity to generate IL 2 in vitro when cultured under appropriate conditions. Taken together, these results suggest that suppression of cell-mediated immune responses in Con A-treated mice results from interruption of the normal generation of IL 2 helper effects necessary for the activation of cytotoxic effector T cells in vivo. PMID:6424952

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

    PubMed

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

    1999-02-01

    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

  4. 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. PMID:1971448

  5. Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

    SciTech Connect

    Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

    1986-03-01

    The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.

  6. Effects of clonidine, prazosin and phentolamine on heart rate and coronary sinus catecholamine concentration during cardioaccelerator nerve stimulation in spinal dogs

    PubMed Central

    Cavero, I.; Dennis, T.; Lefèvre-Borg, Françoise; Perrot, P.; Roach, A.G.; Scatton, B.

    1979-01-01

    1 In spinal dogs, continuous electrical stimulation of the cardioaccelerator nerve produced a transient rise in aortic blood pressure and a sustained increase in both heart rate and coronary sinus blood flow. The latter effects were accompanied by a significant elevation in the coronary sinus plasma noradrenaline concentration without significant changes in the levels of dopamine and adrenaline. The concentrations of the three catecholamines in thoracic aorta plasma were not significantly changed by cardioaccelerator nerve stimulation. 2 Clonidine (20 μg/kg, i.v.), given during cardioaccelerator nerve stimulation, increased both mean aortic blood pressure and coronary sinus blood flow and decreased heart rate and coronary sinus venous plasma noradrenaline overflow. 3 Phentolamine (0.3 mg/kg, i.v.) completely antagonized these effects of clonidine. Prazosin (0.3 mg/kg, i.v.) inhibited by only 43 and 38% the respective reductions in heart rate and noradrenaline overflow elicited by clonidine. 4 On termination of cardioaccelerator stimulation (about 10 min after either prazosin or phentolamine), heart rate and coronary sinus noradrenaline overflow returned to control prestimulation levels. 5 Phentolamine or prazosin, administered alone during stimulation of the cardioaccelerator nerve, increased heart rate and noradrenaline overflow into the coronary sinus plasma. However, intravenous phentolamine and prazosin, in contrast to desipramine (0.3 mg/kg, i.v.) or tyramine (1.0 mg, i.a.), failed to change the tachycardia resulting from the local administration of noradrenaline into the sinus node artery (i.a.). 6 These results show that in spinal dogs the clonidine-induced reduction in heart rate (elevated by electrical stimulation of the cardioaccelerator nerve) is accompanied by a fall in the quantity of noradrenaline overflowing into the coronary sinus plasma. The latter effect is presumably the result of an action of clonidine on cardiac presynaptic

  7. Interdental caries incidence and progression in relation to mutans streptococci suppression after chlorhexidine-thymol varnish treatments in schoolchildren.

    PubMed

    Twetman, S; Petersson, L G

    1999-06-01

    The aim of this study was to evaluate interdental caries incidence and progression in relation to the effect of antibacterial varnish treatments in schoolchildren anticipated at caries risk. After a screening procedure, 110 healthy children (8-10 years) with moderate and high counts of salivary mutans streptococci (MS) were invited to join a 2-year longitudinal study. At baseline, MS were enumerated at all mesial interdental sites of the first permanent molars with a chair-side technique. The children were then treated 3 times within 2 weeks by interdental spot applications with a 1% chlorhexidine/thymol-containing varnish (Cervitec). Follow-up samples of saliva and plaque were collected 1, 3, 6, and 12 months after onset of treat. Caries prevalence, incidence and progression of the selected approximal surfaces were scored from bitewing radiographs exposed at baseline and after 2 years. Sixty-three children of the same age formed a non-varnish-treated reference group. Reduction of caries incidence and progression was dearly dependent on the outcome of the antibacterial treatment. A significantly (P< 0.01) higher progression score was found among children who exhibited a less marked suppression of interdental MS levels compared with those with high suppression and the children of the reference group. The results suggest that a suppression of MS in interdental plaque may be an important event to prevent and arrest approximal caries development in schoolchildren at risk. Monitoring the effect of antibacterial agents in a site-specific way could therefore be advocated. PMID:10480280

  8. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages.

    PubMed

    Pal, Sanjima; Konkimalla, V Badireenath

    2016-06-01

    Any chronic, inflammatory, autoimmune disease (e.g. arthritis) associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN) in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I-IV) induced auto-reactive M1 type monocyte/macrophage model. PMID:27222853

  9. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    PubMed Central

    Pal, Sanjima; Konkimalla, V. Badireenath

    2016-01-01

    Any chronic, inflammatory, autoimmune disease (e.g. arthritis) associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN) in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV) induced auto-reactive M1 type monocyte/macrophage model. PMID:27222853

  10. 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

  11. Suppression of Gαs Synthesis by Simvastatin Treatment of Vascular Endothelial Cells*

    PubMed Central

    Kou, Ruqin; Shiroto, Takashi; Sartoretto, Juliano L.; Michel, Thomas

    2012-01-01

    These studies explore the effects of statins on cyclic AMP-modulated signaling pathways in vascular endothelial cells. We previously observed (Kou, R., Sartoretto, J., and Michel, T. (2009) J. Biol. Chem. 284, 14734–14743) that simvastatin treatment of endothelial cells leads to a marked decrease in PKA-modulated phosphorylation of the protein VASP. Here we show that long-term treatment of mice with simvastatin attenuates the vasorelaxation response to the β-adrenergic agonist isoproterenol, without affecting endothelin-induced vasoconstriction or carbachol-induced vasorelaxation. We found that statin treatment of endothelial cells dose-dependently inhibits PKA activation as assessed by analyses of serine 157 VASP phosphorylation as well as Epac-mediated Rap1 activation. These effects of simvastatin are completely reversed by mevalonate and by geranylgeranyl pyrophosphate, implicating geranylgeranylation as a critical determinant of the stain response. We used biochemical approaches as well as fluorescence resonance energy transfer (FRET) methods with a cAMP biosensor to show that simvastatin treatment of endothelial cells markedly inhibits cAMP accumulation in response to epinephrine. Importantly, simvastatin treatment significantly decreases Gαs abundance, without affecting other Gα subunits. Simvastatin treatment does not influence Gαs protein stability, and paradoxically increases the abundance of Gαs mRNA. Finally, we found that simvastatin treatment inhibits Gαs translation mediated by Akt/mTOR/eIF4/4EBP. Taken together, these findings establish a novel mechanism by which simvastatin modulates β-adrenergic signaling in vascular wall, and may have implications for cardiovascular therapeutics. PMID:22144680

  12. Sulfasalazine Treatment Suppresses the Formation of HLA-B27 Heavy Chain Homodimer in Patients with Ankylosing Spondylitis.

    PubMed

    Yu, Hui-Chun; Lu, Ming-Chi; Huang, Kuang-Yung; Huang, Hsien-Lu; Liu, Su-Qin; Huang, Hsien-Bin; Lai, Ning-Sheng

    2016-01-01

    Human leukocytic antigen-B27 heavy chain (HLA-B27 HC) has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC)₂ via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER) stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS). Sulfasalazine (SSA) is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC)₂ formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC)₂ of peripheral blood mononuclear cells (PBMC), the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI) scores of 23 AS patients. The results indicated that AS patients without (B27-HC)₂ on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC)₂ on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs. PMID:26729099

  13. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 administ...

  15. Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice.

    PubMed

    Liu, Lei; Fujimoto, Masashi; Kawakita, Fumihiro; Nakano, Fumi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-09-01

    The role of vascular endothelial growth factor (VEGF) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The aim of this study was to investigate effects of anti-VEGF therapy on EBI after SAH. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or two dosages (0.2 and 1 μg) of anti-VEGF antibody were randomly administrated by an intracerebroventricular injection. Neuroscore, brain water content, immunoglobulin G staining, and Western blotting were performed to evaluate EBI at 24-48 h. To confirm the role of VEGF, anti-VEGF receptor (VEGFR)-2 (a major receptor of VEGF) antibody was intracerebroventricularly administered and the effects on EBI were evaluated at 24 h. A higher dose, but not a lower dose, of anti-VEGF antibody significantly ameliorated post-SAH neurological impairments and brain edema at 24-48 h post-SAH. Post-SAH blood-brain barrier disruption was also inhibited by anti-VEGF antibody. The protective effects of anti-VEGF antibody were associated with the inhibition of post-SAH induction of VEGF, VEGFR-2, phosphorylated VEGFR-2, interleukin-1β and a matricellular protein tenascin-C (TNC). Anti-VEGFR-2 antibody also suppressed post-SAH neurological impairments and brain edema associated with VEGFR-2 inactivation and TNC downregulation. These findings demonstrated that VEGF causes post-SAH EBI via VEGFR-2 and TNC and that anti-VEGF therapy is effective for post-SAH EBI. PMID:26289408

  16. Counteraction by combined treatment with high dose of oestrogen and somatostatin of mammary growth suppression in mice.

    PubMed

    Nagasawa, H; Koshimizu, U; Sakagami, N

    1988-01-01

    The interaction between somatostatin (SMS) and high doses of oestrogen on mammary gland growth was examined in C3H/He virgin mice. Mammary gland growth was significantly suppressed by the subcutaneous implantation of pellets of oestradiol benzoate diluted to 1/1000 or 1/500 or by injection twice daily of 50ng SMS 201-995 between 25 and 55 days of age. However, the mammary gland growth of mice receiving SMS and oestrogen in combination was markedly stimulated compared to that of mice given the respective agents. These results indicate that the inhibitory effects of somatostatin and oestrogen on mammary growth were apparently counteracted by the treatment in combination. PMID:2908772

  17. 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. PMID:19444752

  18. Suppression of seed rot and preemergence of chickpea by seed treatments with fluorescent pseudomonads in Iran.

    PubMed

    Ahmadzadeh, M; Sharifi-Tehrani, A

    2006-01-01

    Species of Pythium isolated from rotted chickpea seeds and damped-off seedlings and chickpea soils at experimental field of Agriculture faculty of Tehran University in Karaj area that caused seed rot and preemergence damping-off of chickpea were Pyhium ultimum var. ultimum. One of the most important of soilborne fungal pathogens of the chickpea in Iran is seed rot and preemergence damping-off caused by Pythium ultimum Trow. Consequently, growers can expect as much as > 80% reduction in stand and yield if measures are not taken to control Pythium. Currently, most commercial seeds of chickpea are treated with pesticides. Fluorescent pseudomonads applied to seed are known to reduce soilborne diseases of chickpea caused by Pythium spp. In this study rotted chickpea seeds and diseased seedlings and soil samples were collected from experimental field in Karaj. Soils and roots used as sources of bacteria were collected from field. Fluorescent pseudomonads were isolated by plating samples on S1 and King's Medium B (KMB). Bacteria were preserved in 0.1 M MgSO4 for long-term storage; and NAG (containing 2% glucose) slants and plates at 4 degrees C short-term storage. Of 20 fluorescent pseudomonads isolated on S1 medium, 2 isolates selected for next tests. All strains significantly increased emergence as compared to the infested control in greenhouse trial; isolate Pf-4 consistently provided the best protection against Pythium. Seedling emergence from all bacteria seed treatments was statistically lower than the chemical treatments. All strains significantly increased fresh weight of chickpea as compared to the infested control in greenhouse trial. Seed treatment with metalaxyl were statistically better than captan in sterilized soil. In nonsterilized soil collected from the field artificially infested with P. ultimum, all strains significantly increased fresh weight of chickpea as compared to the infested control in greenhouse trial. Seedling emergence from seed treatment

  19. Suppression of oncoprotein Her-2 and DNA damage after treatment with Flavan-3- ol vitis labrusca extract.

    PubMed

    Scola, Gustavo; Fernandes Correia Laurino, Claudia Cilene; Menin, Eveline; Salvador, Mirian

    2013-09-01

    Hepatocellular carcinoma and breast cancer are the most prevalent cancers in the world with high morbidity and mortality. Although there are effective drugs for treating advanced stages of liver and breast cancers, the prognosis for patients with liver cancer remains poor, and patients with breast cancer show considerable mortality. Therefore, it is crucial to explore new therapeutic agents for the inhibition of carcinogenesis. This study examined the anti-carcinogenic effect of Vitis labrusca seed extract (VLE), which is a component of winery waste, on liver (HepG2) and breast cancers (MCF-7) cells. The results found in this study demonstrated VLEinduced DNA damage in liver and breast cancer cells. VLE treatment in both cell lines was accompanied by high NO production and upregulation of p53. A significant decrease in total PARP expression was also found in HepG2 cells. In the MCF-7 cell line, VLE treatment increased the expression of Bax and AIF, and decreased total PARP expression. Surprisingly, VLE suppressed Her-2 expression in HepG2 cells and caused a subtle, but significant downregulation of Her-2 in MCF-7 cells. The possible anti-carcinogenic effect of VLE reported in this study suggests the potential of this extract to be used for the development of novel therapeutic agents for the treatment of different kinds of cancers. PMID:23343084

  20. Suppression of aflatoxin B1- or methyl methanesulfonate-induced chromosome aberrations in rat bone marrow cells after treatment with S-methyl methanethiosulfonate.

    PubMed

    Ito, Y; Nakamura, Y; Nakamura, Y

    1997-10-24

    The suppressive effect of S-methyl methanethiosulfonate (MMTS) on aflatoxin B1 (AFB1)- or methyl methanesulfonate (MMS)-induced chromosome aberrations (CA) in rat bone marrow cells was studied. MMTS significantly suppressed CA induced by both AFB1 (an indirect-acting carcinogen) and MMS (a direct-acting carcinogen). Suppression was observed at all periods (6, 12, 18, 24 and 48 h) after AFB1 or MMS treatment and in all doses of AFB1 (5, 10 and 20 mg/kg) or MMS (50, 75 and 100 mg/kg) investigated. AFB1-induced CA was potently suppressed by MMTS given between 2 h before and 6 h after the AFB1 injection. The suppression of AFB1-induced CA by MMTS paralleled the dose of MMTS when MMTS was given in a dose range of 1-20 mg/kg body weight. MMS-induced CA was potently suppressed by MMTS given between 2 h before and 2 h after the MMS injection. The suppressive effect of MMTS on MMS-induced CA paralleled the dose of MMTS when MMTS was given in a dose range of 1-15 mg/kg body weight. Diphenyl disulfide, which modifies -SH groups in proteins like MMTS, also significantly suppressed both AFB1- and MMS-induced CA. Although other mechanisms are not excluded, the suppression of carcinogen-induced CA by MMTS may result from the ability of MMTS to modify -SH groups in proteins. The juices of cabbage and onion, which contain considerable amounts of MMTS and S-methyl-L-cysteinesulfoxide (the precursor of MMTS), also significantly suppressed AFB1- or MMS-induced CA. These results suggest that MMTS is a possible chemopreventive agent against cancer. PMID:9393623

  1. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    PubMed Central

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. The mean age at onset of the disease was 3.2 years and at investigation 10.7 years. The average attained height equalled -0.3 SD at onset, and -1.0 SD at the time of investigation. Secretion of growth hormone was substantially reduced compared with controls and did not increase during puberty. A prompt rise in growth hormone secretion was seen after injection of growth hormone releasing hormone, but the mean maximum growth hormone concentration was, however, only 25 mU/l. There was no correlation between the 24 hour secretion and growth hormone response to growth hormone releasing hormone, or the time since irradiation. These results confirm earlier work that suggested that girls who had received treatment for acute lymphoblastic leukaemia, that included cranial irradiation, have a comparative growth hormone insufficiency characterised by normal prepubertal growth and slow growth during puberty because of an inability to respond to the increased demands for growth hormone at that time. PMID:2494952

  2. Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats.

    PubMed

    Satake, Kyosuke; Ikeda, Junichi; Tamura, Tadafumi; Amano, Toru; Kobayashi, Katsuya

    2015-10-15

    Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose-dependent manner. Inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation was significantly more potent than that of cetirizine hydrochloride, other antiallergic agent with H1R antagonistic activity, at doses in which both agents exhibit comparable H1R antagonistic activity in rats. These results suggest that H1R antagonistic activity-independent mechanism contribute to the inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation. Olopatadine also significantly inhibited increases in vascular permeability and nerve growth factor production in the skin induced by topical tacrolimus treatment. Thus, the onset of hot flashes in rats is quantitatively determined by measuring the skin temperature and olopatadine attenuates hot flashes induced by topical tacrolimus ointment in rats, suggesting that the combination application with olopatadine and tacrolimus ointment is useful for improving medication adherence with tacrolimus ointment treatment in patients with atopic dermatitis. PMID:26362749

  3. 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.

  4. Suppression of Myocardial Injury Markers following Percutaneous Coronary Interventions by Pre-treatment with Carvedilol

    PubMed Central

    Moloudi, Abdolrasoul; Sabzi, Feridoun; Rashidi, Shirin

    2012-01-01

    Background Retrospective studies and clinical trials have indicated that β-receptor blockers have an influential role in improving survival and reducing risk of recurrent infarction in patients with myocardial infarction. However, there is still controversy regarding the effects of β-receptor blockers on the markers of myocardial infarction following percutaneous coronary interventions (PCI). Objective The aim of this study was to evaluate the pre-treatment effect of Carvedilol on markers of myocardial injury in patients undergoing elective PCI. Method and Materials In this clinical trial patients undergoing elective PCI were categorized randomly in the Carvedilol group including 100 patients who received two doses of 12.5 mg, 6 and 12 hours prior to PCI, and the control group (105 patients). Blood samples were obtained to analyse cardiac biomarker, 12 and 24 hours after PCI. Results The clinical features were not significantly different between the two groups. A increase in the level of Troponin I was observed in the control group 24 hours following PCI (P=0.042), whereas this rise in troponin I was slight and insignificant in the Carvedilol group (P>0.05). some difference was observed between the two groups in regard to the level of CPK-MB after PCI (P=0.041). Conclusion The findings of our study indicate that pre-treatment with Carvedilol confers cardio-protection by limiting the rise of markers of myocardial injury following PCI. PMID:24757599

  5. 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.

  6. 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

  7. IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.

    PubMed

    Paquin-Proulx, Dominic; Santos, Bianca A N; Carvalho, Karina I; Toledo-Barros, Myrthes; Barreto de Oliveira, Ana Karolina; Kokron, Cristina M; Kalil, Jorge; Moll, Markus; Kallas, Esper G; Sandberg, Johan K

    2013-01-01

    Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection. PMID:24130688

  8. Autologous formalin-fixed tumor vaccine suppressed re-recurrence of HCV-related hepatocellular carcinoma following 29 unsuccessful treatments with extensive conventional therapy: a case report.

    PubMed

    Inui, Toshio; Ohno, Tadao

    2012-01-01

    Treatment of hepatocellular carcinoma (HCC) with autologous formalin-fixed tumor vaccine after primary resection has been shown to suppress the recurrence of hepatitis B virus-associated HCC, but the effect of this treatment on hepatitis C virus (HCV)-related disease has not yet been clarified. Here, we report a case of a patient with repeat recurrent HCC that was associated with HCV who had endured 29 episodes of HCC recurrence despite a variety of therapy using conventional methods. Finally, treatment with a single course of autologous formalin-fixed tumor vaccine resulted in suppression of potential further re-recurrence of HCC for more than 43 months without any additional treatment. PMID:22789008

  9. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  10. Suppression of caries-related microorganisms in dentine lesions after short-term chlorhexidine or antibiotic treatment.

    PubMed

    Wicht, Michael J; Haak, Rainer; Schütt-Gerowitt, Heidi; Kneist, Susanne; Noack, Michael J

    2004-01-01

    This study investigated the efficiency of a chlorhexidine varnish and an antibiotic paste in suppressing the cultivable microflora of deep dentine cavities in a stepwise excavation procedure. Subsequent to enamel preparation and removal of the central biomass, infected dentine was sampled from the cavity floor. Ten cavities each were either covered with the 1% chlorhexidine- and 1% thymol-containing varnish Cervitec (CE), the demeclocycline hydrocortisone-containing ointment Ledermix (LE) or received no treatment as control (CO). A compomer composite was used as intermediate restorative. Cavities were reassessed after 6 weeks and again dentine samples were microbiologically investigated for total viable counts, mutans streptococci and lactobacilli. After 6 weeks a significant reduction of the total viable counts was observed in the LE group (p = 0.011) compared to the control, whereas no differences were found in the CE group (p > 0.05). Mutans streptococci were rarely recovered at baseline and after 6 weeks. Compared to the CO group counts of lactobacilli were significantly reduced in the CE and LE groups (p < 0.05). Lactobacillus species were frequently recovered at baseline and after 6 weeks of observation. Lactobacillus rhamnosus was the predominant species in all samples investigated. Application of CE or LE resulted in reduced counts of lactobacilli after a period of 6 weeks. Although none of the materials completely eliminated the viable microorganisms, the use of LE was more effective than CE in reducing the total anaerobic microorganisms associated with carious dentine. PMID:15316187

  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. 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

  13. Treatment with connexin 46 siRNA suppresses the growth of human Y79 retinoblastoma cell xenografts in vivo.

    PubMed

    Burr, Diana B; Molina, Samuel A; Banerjee, Debarshi; Low, Derek M; Takemoto, Dolores J

    2011-04-01

    Tumors with a hypoxic component, including human Y79 retinoblastoma cells, express a specific gap junction protein, Connexin 46 (Cx46), which is usually only found in naturally hypoxic tissues such as the differentiated lens. The aim of this study was to investigate if Cx46 downregulation would suppress Y79 tumor formation in vivo. Five-week old nude mice were subcutaneously implanted with human Y79 retinoblastoma cells and treated with intratumor siRNA injections of 30 μg Cx46 siRNA (n = 6), 30 μg non-silencing siRNA (n = 6), or no siRNA treatment (n = 6) every 2 days for a maximum of 10 treatments. Tumor volume (TV) was calculated from the recorded caliper measurements of length and width. Excised tumors were measured and weighed. Western blot analyses were performed to evaluate Cx46 and Cx43 expression in tumors which received Cx46 siRNA, non-silencing siRNA, or no siRNA treatment. Tumor histopathology was used to assess tumor features. Cx46 siRNA treated Y79 tumors had a reduced TV (287 mm(3) ± 77 mm(3)) when compared to the tumors of mice receiving the negative control siRNA (894 mm(3) ± 218 mm(3); P ≤ 0.03) or no siRNA (1068 mm(3) ± 192 mm(3); P ≤ 0.002). A 6-fold knockdown of Cx46 and a 3-fold rise in Cx43 protein expression was observed from western blots of tumors treated with Cx46 siRNA compared to mice treated with non-silencing siRNA. Knockdown of Cx46 with siRNA had an antitumor effect on human Y79 retinoblastoma tumors in the nude mouse model. The results suggest that anti-Cx46 therapy may be a potential target in the future treatment of retinoblastoma. PMID:21320488

  14. Suppression of BCG cell wall induced delayed-type hypersensitivity by BCG pre-treatment. I. Induction of adherent suppressor cells by live BCG injection and their characterization.

    PubMed Central

    Kato, K; Yamamoto, K I; Kakinuma, M; Ishihara, C; Azuma, I

    1981-01-01

    Previous injections of live Bacillus Calmette-Guérin (BCG) in mice produced a suppression of delayed-type hypersensitivity (DTH) induced by oil-treated BCG cell walls (CW). This phenomenon was analysed by the macrophage migration inhibition (MI) test in which peritoneal exudate cells (PEC) from live BCG-injected mice were mixed with PEC from BCG CW-immunized mice, with the result that the former cells suppressed the MI activity in the latter. We considered the Mi test to be a reliable method for demonstrating the existence of suppressor cells induced by the injection of live BCG. Moreover, we found that the adherent cells of PEC possessed a suppressive effect which was retained even after treatment with either anti-mouse Ig or anti-brain associated theta (BA theta) antigen; that the PEC from mice injected with live BCG on at least the 12th day before cell harvesting showed the suppression; and that the suppression operated across the H-2 barrier. PMID:6450731

  15. 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

  16. Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009

    PubMed Central

    Hanna, David B.; Buchacz, Kate; Gebo, Kelly A.; Hessol, Nancy A.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, P. Todd; Moore, Richard D.; Napravnik, Sonia; Patel, Pragna; Silverberg, Michael J.; Sterling, Timothy R.; Willig, James H.; Lau, Bryan; Althoff, Keri N.; Crane, Heidi M.; Collier, Ann C.; Samji, Hasina; Thorne, Jennifer E.; Gill, M. John; Klein, Marina B.; Martin, Jeffrey N.; Rodriguez, Benigno; Rourke, Sean B.; Gange, Stephen J.; Benson, A.; Bosch, Ronald J.; Collier, Ann C.; Boswell, Stephen; Grasso, Chris; Mayer, Ken; Hogg, Robert S.; Harrigan, Richard; Montaner, Julio; Cescon, Angela; Brooks, John T.; Buchacz, Kate; Gebo, Kelly A.; Moore, Richard D.; Rodriguez, Benigno; Horberg, Michael A.; Silverberg, Michael J.; Thorne, Jennifer E.; Goedert, James J.; Jacobson, Lisa P.; Klein, Marina B.; Rourke, Sean B.; Burchell, Ann; Rachlis, Anita R.; Hunter-Mellado, Robert F.; Mayor, Angel M.; Gill, M. John; Deeks, Steven G.; Martin, Jeffrey N.; Saag, Michael S.; Mugavero, Michael J.; Willig, James; Eron, Joseph J.; Napravnik, Sonia; Kitahata, Mari M.; Crane, Heidi M.; Justice, Amy C.; Dubrow, Robert; Fiellin, David; Sterling, Timothy R.; Haas, David; Bebawy, Sally; Turner, Megan; Gange, Stephen J.; Anastos, Kathryn; Moore, Richard D.; Saag, Michael S.; Gange, Stephen J.; Kitahata, Mari M.; McKaig, Rosemary G.; Justice, Amy C.; Freeman, Aimee M.; Moore, Richard D.; Freeman, Aimee M.; Lent, Carol; Platt, Aaron; Kitahata, Mari M.; Van Rompaey, Stephen E.; Crane, Heidi M.; Webster, Eric; Morton, Liz; Simon, Brenda; Gange, Stephen J.; Abraham, Alison G.; Lau, Bryan; Althoff, Keri N.; Zhang, Jinbing; Jing, Jerry; Golub, Elizabeth; Modur, Shari; Hanna, David B.; Rebeiro, Peter; Wong, Cherise; Mendes, Adell

    2013-01-01

    Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes. Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness. Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001). Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide. PMID:23315317

  17. 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.

  18. 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

  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. PMID:24892897

  20. Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems

    PubMed Central

    Liu, Fanwei; Shimakami, Tetsuro; Murai, Kazuhisa; Shirasaki, Takayoshi; Funaki, Masaya; Honda, Masao; Murakami, Seishi; Yi, Minkyung; Tang, Hong; Kaneko, Shuichi

    2016-01-01

    Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir, and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotype 1a in cell cultures. We found that combination treatments with anti-miR-122 and a DAA had additive or synergistic antiviral effects. The EC50 values of simeprevir in simeprevir-resistant mutants were significantly decreased by combining simeprevir with anti-miR-122. A similar reduction in EC50 in daclatasvir-resistant mutants was achieved by combining daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but the levels later rebounded. DAA-resistant mutants were less frequently observed in combination treatments than in DAA single treatments. In summary, the addition of miR-122 antagonism to DAA single treatments had additive or synergistic antiviral effects and helped to efficiently suppress HCV replication and the emergence of DAA-resistant mutants. PMID:27484655

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

    PubMed Central

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

    2014-01-01

    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. PMID:25107642

  2. Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment

    PubMed Central

    Li, Pei-Tzu; Tsai, Yi-Jane; Lee, Ming-Jen; Chen, Chin-Tin

    2015-01-01

    Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ0 cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation. PMID:26473836

  3. Bone mineral density and bone microarchitecture after long-term suppressive levothyroxine treatment of differentiated thyroid carcinoma in young adult patients.

    PubMed

    Mendonça Monteiro de Barros, Graziella; Madeira, Miguel; Vieira Neto, Leonardo; de Paula Paranhos Neto, Francisco; Carvalho Mendonça, Laura Maria; Corrêa Barbosa Lima, Inayá; Corbo, Rossana; Fleiuss Farias, Maria Lucia

    2016-07-01

    Bone mineral density (BMD) seems not to be decreased in young patients given long-term suppressive doses of levothyroxine (LT4), but information regarding the bone microstructure in these patients is lacking. The aim of this study was to determine whether supraphysiologic doses of LT4, initiated during childhood or adolescence for treatment of differentiated thyroid carcinoma (DTC), have any detrimental effects on bone microarchitecture as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Seventeen patients (27.3 ± 7.1 years old) with DTC with subclinical hyperthyroidism since adolescence and 34 healthy volunteers matched for age, sex, and body mass index were studied by dual-energy X-ray absorptiometry (DXA) to determine the areal BMD at the lumbar spine, hip, and proximal third of the radius. Volumetric BMD and structural parameters of the trabecular and cortical bone were assessed by HR-pQCT of the distal radius and distal tibia. DTC patients were given suppressive doses of LT4 starting at a mean age of 12.6 years, and the mean duration of treatment was 14.2 years. In DTC patients, clinical parameters did not correlate with DXA or HR-pQCT parameters. No differences were found between the patients and controls with respect to BMD and Z scores at any site evaluated by DXA, and no differences were found in the bone microstructure parameters evaluated by HR-pQCT. This cross-sectional study suggests that long-standing suppressive therapy with LT4 during the attainment of peak bone mass may have no significant adverse effects on bone density or microarchitecture. PMID:26056020

  4. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

    SciTech Connect

    Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori . E-mail: kuwabara@vetmed.hokudai.ac.jp

    2007-05-01

    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-{beta}-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth.

  5. Photodynamic treatment (ALA-PDT) suppresses the expression of the oncogenic Bcr-Abl kinase and affects the cytoskeleton organization in K562 cells.

    PubMed

    Pluskalová, Michaela; Peslová, Gabriela; Grebenová, Dana; Halada, Petr; Hrkal, Zbynek

    2006-06-01

    K562 is the chronic myelogenous leukemia (CML)-derived cell line that expresses high levels of chimeric oncoprotein Bcr-Abl. The deregulated (permanent) kinase activity of Bcr-Abl leads to continuous proliferation of K562 cells and their resistance to the apoptosis promotion by conventional drugs. The photodynamic treatment (PDT) based on the application of 5-aminolevulinic acid (ALA) and irradiation with blue light (ALA-PDT) resulted in the suppression of K562 cells proliferation. It was followed by a necrosis-like cell death [K. Kuzelová, D. Grebenová, M. Pluskalová, I. Marinov, Z. Hrkal, J. Photochem. Photobiol. B 73 (2004) 67-78]. ALA-PDT led to the perturbation of the Hsp90/p23 multichaperone complex of which the Bcr-Abl is the client protein. Bcr-Abl protein was suppressed whereas the bcr-abl mRNA level was not affected. Further on, we observed several changes in the cytoskeleton organization. We detected ALA-PDT-mediated disruption of filamental actin structure using FITC-Phalloidin staining. In connection with this we uncovered certain cytoskeleton organizing proteins involved in the cell response to the treatment. Among these proteins, Septin2, which plays a role in maintaining actin bundles, was suppressed. Another one, PDZ-LIM domain protein 1 (CLP36) was altered. This protein acts as an adaptor molecule for LIM-kinase which phosphorylates and thus inactivates cofilin. Cofilin was indeed dephosphorylated and could thus be activated and operate as an actin-depolymerizing factor. We propose the scheme of molecular response of K562 cells to ALA-PDT. PMID:16495075

  6. 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.

  7. Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.

    PubMed

    Niikawa, Miki; Shin, Seizai; Nagase, Hisamitsu

    2007-01-01

    In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre-treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer. PMID:17275250

  8. 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

  9. Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy combined with doxorubicin treatment

    PubMed Central

    Van Pham, Phuc; Vu, Ngoc Bich; Duong, Thuy Thanh; Nguyen, Tam Thanh; Truong, Nhung Hai; Phan, Nhan Lu Chinh; Vuong, Tue Gia; Pham, Viet Quoc; Nguyen, Hoang Minh; Nguyen, Kha The; Nguyen, Nhung Thi; Nguyen, Khue Gia; Khat, Lam Tan; Van Le, Dong; Truong, Kiet Dinh; Phan, Ngoc Kim

    2012-01-01

    Background Breast cancer stem cells with a CD44+CD24− phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44+CD24− breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment. Methods Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44+CD24− cells. To track CD44+CD24− cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control. Results The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was significantly decreased by 4.38-fold compared with that of the control group. Conclusion These results support a new strategy for breast cancer treatment by combining gene therapy with chemotherapy. PMID:22649280

  10. 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

  11. 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...

  12. An open-label, multicentre study to assess the safety and efficacy of a novel reflux suppressant (Gaviscon Advance) in the treatment of heartburn during pregnancy.

    PubMed

    Lindow, S W; Regnéll, P; Sykes, J; Little, S

    2003-04-01

    This study investigated the efficacy and safety of a novel reflux suppressant, Gaviscon Advance, in the treatment of heartburn during pregnancy. The study was an open-label, multicentre, phase IV study in general practice and antenatal clinics in the UK and Republic of South Africa. Pregnant women (< or = 38 weeks gestation; n=150) aged 18-40 years suffering from heartburn were instructed to take Gaviscon Advance 5-10 ml, as required, to relieve symptoms. The main outcome measures were the efficacy rating of the study medication by the investigator and women after four weeks using a five-point efficacy scale. After four weeks the investigators' and women's rating of efficacy was 'very good' or 'good' in 88% and 90% of women, respectively. Most women (57%, n=83) reported symptom relief within 10 minutes. Thus Gaviscon Advance effectively and rapidly treats heartburn during pregnancy. Its use during pregnancy presents no known significant safety concerns for mother or child. PMID:12723718

  13. Favourable outcome in idiopathic ventricular fibrillation with treatment aimed at prevention of high sympathetic tone and suppression of inducible arrhythmias.

    PubMed Central

    Crijns, H. J.; Wiesfeld, A. C.; Posma, J. L.; Lie, K. I.

    1995-01-01

    OBJECTIVE--In the absence of an obvious cause for cardiac arrest, patients with idiopathic ventricular fibrillation are difficult to manage. A subset of patients has inducible arrhythmias. In others sympathetic excitation plays a role in the onset of the cardiac arrest. This study evaluates a prospective stepped care approach in the management of idiopathic ventricular fibrillation, with therapy first directed at induced arrhythmias and secondly at adrenergic trigger events. SETTING--University Hospital. PATIENTS--10 consecutive patients successfully resuscitated from idiopathic ventricular fibrillation. INTERVENTIONS--Programmed electrical stimulation to determine inducibility, followed by serial drug treatment. Assessment of pre-arrest physical activity and mental stress status by interview, followed by beta blockade. Cardioverter-defibrillator implantation in non-inducible patients not showing significant arrest related sympathetic excitation. MAIN OUTCOME MEASURE--Recurrent cardiac arrest or ventricular tachycardia. RESULTS--Five patients were managed with serial drug treatment and four with beta blockade. In one patient a defibrillator was implanted. During a median follow up of 2.8 years (range 6 to 112 months) no patient died or experienced defibrillator shocks. One patient had a recurrence of a well tolerated ventricular tachycardia on disopyramide. CONCLUSIONS--Idiopathic ventricular fibrillation may be related to enhanced sympathetic activation. Prognosis may be favourable irrespective of the method of treatment. Whether the present approach enhances prognosis of idiopathic ventricular fibrillation remains to be determined. However, it may help to avoid potentially hazardous antiarrhythmic drugs or obviate the need for implantation of cardioverter-defibrillators. PMID:7488456

  14. 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

  15. Suppression of current fluctuations in a crossed E×B field system for low-voltage plasma immersion treatment

    NASA Astrophysics Data System (ADS)

    Levchenko, I.; Keidar, M.; Ostrikov, K.; Yu, M. Y.

    2006-01-01

    Plasma transport in a hybrid dc vacuum arc plasma source for ion deposition and plasma immersion treatment is considered. It is found that external crossed electric and magnetic fields near the substrate can significantly reduce the relative amplitude of ion current fluctuations If at the substrate surface. In particular, If decreases with the applied magnetic field when the bias voltage exceeds 300 V, thus allowing one to reduce the deviations from the rated process parameters. This phenomenon can be attributed to an interaction between the metal-plasma jet from the arc source and the discharge plasma in the crossed fields.

  16. [Effect of plasma-treatment on suppression of drug adsorption to the surface of plastic infusion bag].

    PubMed

    Furuta, Y; Nishimura, K; Kuzuya, M

    1999-12-01

    Plastics has been widely used at the hospitals and dominates the field of the manufacture of infusion bag sets and packaging materials as a disposable product. Recently, it has been reported, however, that expected drug effects could not be obtained owing mainly to the drug adsorption to the surface of plastic bags observed when several injection drugs such as nitroglycerin, isosorbide dinitrate, diazepam, and insulin were injected mixedly into a certain plastic intravenous bags. And there is a possibility of the occurrence of chemical reactions between the added drugs and the surface of plastic bags. We also can not deny the possibility of the dissolution of softener from the plastic bags. On the other hand, we have been working on the nature of plasma treatment of polymer surfaces by irradiation of low temperature plasma and its pharmaceutical application studies. In this study, we obtained the data concerning the effect of plasma treatment on the reduction of adsorption of insulin to the surface of ethylene-vinylacetate (EVA) bag. PMID:10630098

  17. 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.

  18. Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1 beta in pigs in vivo.

    PubMed Central

    Ito, A; Shimokawa, H; Kadokami, T; Fukumoto, Y; Owada, M K; Shiraishi, T; Nakaike, R; Takayanagi, T; Egashira, K; Takeshita, A

    1995-01-01

    We recently demonstrated that chronic treatment with IL-1 beta induces coronary arteriosclerotic changes and vasospastic responses to autacoids in pigs in vivo and that those responses are importantly mediated by PDGF. The receptors for PDGF and other major growth factors are known to have tyrosine kinase activity. We therefore investigated the effects of a selective tyrosine kinase inhibitor, ST 638, on those responses induced by IL-1 beta in our swine model. Intimal thickening and coronary vasospastic responses to serotonin and histamine were induced at the site of the coronary artery where IL-1 beta was chronically and locally applied. These responses were significantly suppressed in a dose-dependent manner by cotreatment with ST 638. In addition, ST 494, which is an inactive form of ST 638, did not inhibit those responses. The treatment with ST 638 alone did not affect the coronary vasoconstricting responses to the autacoids. Immunoblotting using an antibody to phosphotyrosines confirmed the inhibitory effects of ST 638 on the tyrosine phosphorylations induced by IL-1 beta. These results thus suggest that tyrosine kinase activation may play an important role in mediating the effects of IL-1 beta, while also suggesting that ST 638 has an inhibitory effect on the arteriosclerotic changes and vasospastic responses to autacoids in our swine model in vivo. Images PMID:7657803

  19. Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

    SciTech Connect

    Pearce, Andrew; Choo, Richard . E-mail: choo.c@mayo.edu; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

    2006-05-01

    Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.

  20. 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. PMID:27102611

  1. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    PubMed Central

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  2. Topical glucocorticoid or pimecrolimus treatment suppresses thymic stromal lymphopoietin-related allergic inflammatory mechanism in an oxazolone-induced atopic dermatitis murine model.

    PubMed

    Yoon, Na Young; Jung, Min young; Kim, Dong Hye; Lee, Hae Jin; Choi, Eung Ho

    2015-09-01

    Congenitally or early impaired skin barrier as the first event starting the 'atopic march' in atopic dermatitis (AD) patients can increase allergen penetration that results in sensitization, even in the airways, followed by asthma and allergic rhinitis. Thymic stromal lymphopoietin (TSLP) is a cytokine existing in high levels in AD skin and is considered as a novel therapeutic target for atopic disease. We generated oxazolone (Ox)-induced AD-like (Ox-AD) hairless mice and divided them into four groups according to the therapeutic challenges: topical glucocorticoid, pimecrolimus, emollient, and control (acetone-only treated). We assessed the functional studies of skin barrier, epidermal expressions of differentiation markers, IL-1α, TNF-α, proteinase-activated receptor-2 (PAR-2), TSLP and antimicrobial peptides (AMP), and serum IgE in each group. Topical glucocorticoid or pimecrolimus treatment improved AD-like skin lesions and barrier functions, and restored the epidermal expression of differentiation markers, IL-1α, TNF-α, PAR-2, and TSLP, in Ox-AD mice. The improvement was relatively better with the glucocorticoid than pimecrolimus. Epidermal AMP expression was restored by topical glucocorticoid, but not pimecrolimus. Our result showed that topical glucocorticoid or pimecrolimus improved the AD-like skin lesions and barrier impairment by suppressing TSLP-related allergic inflammation. PMID:25786383

  3. 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.

  4. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro.

    PubMed

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

  5. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

    PubMed Central

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

  6. Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1α/VEGF secretion axis

    PubMed Central

    Wang, Yaochun; Tang, Shouching; Sun, Xin; Feng, Xuefei; Li, Yan; Bao, Gang; Li, Pingping; Mao, Xiaona; Wang, Maode; Liu, Peijun

    2015-01-01

    Anti-angiogenesis is currently considered as one of the major antitumor strategies for its protective effects against tumor emergency and later progression. The anti-diabetic drug metformin has been demonstrated to significantly inhibit tumor angiogenesis based on recent studies. However, the mechanism underlying this anti-angiogenic effect still remains an enigma. In this study, we investigated metformin-induced inhibitory effect on tumor angiogenesis in vitro and in vivo. Metformin pretreatment significantly suppressed tumor paracrine signaling-induced angiogenic promotion even in the presence of heregulin (HRG)-β1 (a co-activator of HER2) pretreatment of HER2+ tumor cells. Similar to that of AG825, a specific inhibitor of HER2 phosphorylation, metformin treatment decreased both total and phosphorylation (Tyr 1221/1222) levels of HER2 protein and significantly reduced microvessel density and the amount of Fitc-conjugated Dextran leaking outside the vessel. Furthermore, our results of VEGF-neutralizing and -rescuing tests showed that metformin markedly abrogated HER2 signaling-induced tumor angiogenesis by inhibiting VEGF secretion. Inhibition of HIF-1α signaling by using RNAi or YC-1, a specific inhibitor of HIF-1α synthesis, both completely diminished mRNA level of VEGF and greatly inhibited endothelial cell proliferation promoted by HER2+ tumor cell-conditioned medium in both the absence and presence of HRG-β1 pretreatment. Importantly, metformin treatment decreased the number of HIF-1α nucleus positive cells in 4T1 tumors, accompanied by decreased microvessel density. Our data thus provides novel insight into the mechanism underlying the metformin-induced inhibition of tumor angiogenesis and indicates possibilities of HIF-1α-VEGF signaling axis in mediating HER2-induced tumor angiogenesis. PMID:26625311

  7. Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1α/VEGF secretion axis.

    PubMed

    Wang, Jichang; Li, Guangyue; Wang, Yaochun; Tang, Shouching; Sun, Xin; Feng, Xuefei; Li, Yan; Bao, Gang; Li, Pingping; Mao, Xiaona; Wang, Maode; Liu, Peijun

    2015-12-29

    Anti-angiogenesis is currently considered as one of the major antitumor strategies for its protective effects against tumor emergency and later progression. The anti-diabetic drug metformin has been demonstrated to significantly inhibit tumor angiogenesis based on recent studies. However, the mechanism underlying this anti-angiogenic effect still remains an enigma. In this study, we investigated metformin-induced inhibitory effect on tumor angiogenesis in vitro and in vivo. Metformin pretreatment significantly suppressed tumor paracrine signaling-induced angiogenic promotion even in the presence of heregulin (HRG)-β1 (a co-activator of HER2) pretreatment of HER2+ tumor cells. Similar to that of AG825, a specific inhibitor of HER2 phosphorylation, metformin treatment decreased both total and phosphorylation (Tyr 1221/1222) levels of HER2 protein and significantly reduced microvessel density and the amount of Fitc-conjugated Dextran leaking outside the vessel. Furthermore, our results of VEGF-neutralizing and -rescuing tests showed that metformin markedly abrogated HER2 signaling-induced tumor angiogenesis by inhibiting VEGF secretion. Inhibition of HIF-1α signaling by using RNAi or YC-1, a specific inhibitor of HIF-1α synthesis, both completely diminished mRNA level of VEGF and greatly inhibited endothelial cell proliferation promoted by HER2+ tumor cell-conditioned medium in both the absence and presence of HRG-β1 pretreatment. Importantly, metformin treatment decreased the number of HIF-1α nucleus positive cells in 4T1 tumors, accompanied by decreased microvessel density. Our data thus provides novel insight into the mechanism underlying the metformin-induced inhibition of tumor angiogenesis and indicates possibilities of HIF-1α-VEGF signaling axis in mediating HER2-induced tumor angiogenesis. PMID:26625311

  8. Treatment with Tie2-siRNA in combination with carboplatin suppresses the growth of Ishikawa human endometrial carcinoma cell xenografts in vivo

    PubMed Central

    GUO, FEIFEI; XUN, QINGYING; ZHOU, HUAIJUN

    2013-01-01

    It is well-known that tumor angiogenesis is important in cancer development, and studies on blocking angiogenesis to treat tumors have become one of the most promising and active fields in anticancer research. The present study investigated the effect of siRNA targeting the tyrosine kinase receptor 2 (Tie2) gene in combination with carboplatin in a mouse model of endometrial carcinoma in an attempt to elucidate the role of Tie2 in the carcinogenesis and progression of endometrial carcinoma via angiogenesis, in order to establish a basis for the development of complementary molecule targeting and chemotherapeutic actions. Ishikawa cells were used to establish a human endometrial carcinoma nude mouse tumor xenograft model. Tie2-siRNA (20 μg/mouse) and/or carboplatin (25.0 mg·kg−1) were administered as the treatment strategy. Real-time PCR and western blotting were used to evaluate the expression levels of Tie2 mRNA and protein and immunohistochemistry was used to assess the vessel density of the tumor tissues. The present data demonstrated that Tie2-siRNA and/or carboplatin were able to suppress the growth of endometrial xenografts in vivo and attenuate the expression of Tie2 mRNA and protein, as assessed by real-time PCR and western blotting. Furthermore, immunohistochemical assessment showed that the vessel density of the tumors decreased with treatment. The present results suggest that treatment with Tie2-siRNA or carboplatin alone was able to inhibit the growth of human endometrial carcinoma nude mouse xenografts markedly and decrease the expression of Tie2. The combination of Tie2-siRNA and carboplatin increased the therapeutic effect of carboplatin which may eliminate the tumor microenvironment, increase the apoptosis of tumor cells, normalize the abnormal tumor vessels and increase the efficiency of chemotherapy for endometrial carcinoma with carboplatin. The synergy of Tie2-siRNA in combination with carboplatin may involve the regulation of other

  9. Combination External Beam Radiation and Brachytherapy Boost With Androgen Suppression for Treatment of Intermediate-Risk Prostate Cancer: An Initial Report of CALGB 99809

    SciTech Connect

    Hurwitz, Mark D.; McGinnis, Lamar S.; Keuttel, Michael R.; DiBiase, Steven J.; Small, Eric J.

    2008-11-01

    Purpose: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here. Materials and Methods: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either {sup 125}I or {sup 103}Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems. Results: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort. Conclusions: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control.

  10. Experimental evaluation of a spinning-mode acoustic-treatment design concept for aircraft inlets. [suppression of YF-102 engine fan noise

    NASA Technical Reports Server (NTRS)

    Heidelberg, L. J.; Rice, E. J.; Homyak, L.

    1980-01-01

    An aircraft-inlet noise suppressor method based on mode cutoff ratio was qualitatively checked by testing a series of liners on a YF-102 turbofan engine. Far-field directivity of the blade passing frequency was used extensively to evaluate the results. The trends and observations of the test data lend much qualitative support to the design method. The best of the BPF liners attained a suppression at design frequency of 19 dB per unit length-diameter ratio. The best multiple-pure-tone linear attained a remarkable suppression of 65.6 bB per unit length-diameter ratio.

  11. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  12. Dexamethasone suppression test

    MedlinePlus

    Dexamethasone suppression test measures whether adrenocorticotrophic hormone ( ACTH ) secretion by the pituitary can be suppressed. ... During this test, you will receive dexamethasone. This is a strong ... your blood is drawn so that the cortisol level in your blood ...

  13. 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 ...

  14. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  15. Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice.

    PubMed

    Sae-Wong, Chutha; Mizutani, Nobuaki; Kangsanant, Sureeporn; Yoshino, Shin

    2016-05-15

    Fab fragments (Fabs), which lack effector functions due to the absence of the Fc portion, maintain the ability to bind to specific allergens. In the present study, we examined whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) were able to regulate allergen-induced atopic dermatitis-like skin lesions in mice. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE mAb were repeatedly challenged with OVA applied to the skin after sodium dodecyl sulfate treatment. Fabs prepared by the digestion of anti-OVA IgG1 mAb (O1-10) with papain were applied to the skin 30min before the OVA challenges followed by measurement of clinical symptoms including erythema/hemorrhage, edema, scarring/dryness, and excoriation/erosion of the skin. Treatment with O1-10 Fabs, but not intact O1-10, showed inhibition of clinical symptoms (P<0.01) induced by the repeated OVA challenges in the sensitized mice; O1-10 Fabs suppressed histological changes such as epidermal hyperplasia (P<0.01) and the accumulation of mast cells (P<0.01) and neutrophils (P<0.01). Furthermore, treatment with O1-10 Fabs inhibited the increase in levels of IL-13 (P<0.01) and IL-17A production (P<0.05) in the lymph nodes of the sensitized mice. Additionally, the increased level of OVA in serum following the repeated OVA challenges in the sensitized mice was reduced by the treatment (P<0.05). These results suggest that topical application of pathogenic allergen-specific IgG1 mAb Fabs to the skin of mice is effective in suppressing allergen-induced atopic dermatitis-like skin lesions, suggesting that allergen-specific mAb Fabs could be used as a tool to regulate allergen-induced atopic dermatitis. PMID:26970183

  16. 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?

  17. 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

  18. 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. PMID:23209926

  19. 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...

  20. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients

    PubMed Central

    Baril, Jean-Guy; Angel, Jonathan B.; Gill, M. John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

    2016-01-01

    Objective We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. Methods A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Results Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. Conclusions The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here

  1. Combined treatment of epigallocatechin gallate and Coenzyme Q10 attenuates cisplatin-induced nephrotoxicity via suppression of oxidative/nitrosative stress, inflammation and cellular damage.

    PubMed

    Fatima, Sabiha; Al-Mohaimeed, Noura; Al-Shaikh, Yazeed; Tyagi, Poonam; Banu, Naheed; Hasan, Shirin; Arjumand, Sadia

    2016-08-01

    Cisplatin (CP), a platinum based anticancer drug is used as one of the first-line therapy for the treatment of different types of solid tumors. However, CP-induced side effects particularly, nephrotoxicity is a major concern. A single nephrotoxic dose (7 mg/kg body weight) of CP was administered in rats with or without, pre and post combined multidoses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight respectively). CP administration resulted in marked increase in the nephrotoxic parameters with alterations in the oxidative and nitrosative stress markers. The concentration of inflammatory, as well as apoptotic markers were markedly up-regulated in the kidney of the CP-treated group. Furthermore, CP resulted in histological injury in the renal tissues. Combined antioxidant treatment significantly (p < 0.01) attenuated CP-induced oxidative stress, nitrosative stress, inflammatory and apoptotic parameters. Moreover, an improvement in the histopathological changes confirmed the nephroprotective effect of antioxidant treatment. In conclusion, our study indicates that the combinatorial multidoses of EGCG and CoQ10 ameliorate the cisplatin-mediated pathogenesis by improving renal oxidative/nitrosative status, inflammation and apoptosis and thus can be used as a promising protective agent to increase the efficacy of the drug by minimizing its major side effect i.e. nephrotoxicity. PMID:27265264

  2. Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.

    PubMed Central

    Zehender, M; Hohnloser, S; Geibel, A; Furtwängler, A; Olschewski, M; Meinertz, T; Just, H

    1992-01-01

    OBJECTIVE--To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS--Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS--One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS--Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS--Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS--A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders

  3. Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS

    PubMed Central

    Savarino, Andrea; Pistello, Mauro; D'Ostilio, Daniela; Zabogli, Elisa; Taglia, Fabiana; Mancini, Fabiola; Ferro, Stefania; Matteucci, Donatella; De Luca, Laura; Barreca, Maria Letizia; Ciervo, Alessandra; Chimirri, Alba; Ciccozzi, Massimo; Bendinelli, Mauro

    2007-01-01

    Background Treatment of feline immunodeficiency virus (FIV) infection has been hampered by the absence of a specific combination antiretroviral treatment (ART). Integrase strand transfer inhibitors (INSTIs) are emerging as a promising new drug class for HIV-1 treatment, and we evaluated the possibility of inhibiting FIV replication using INSTIs. Methods Phylogenetic analysis of lentiviral integrase (IN) sequences was carried out using the PAUP* software. A theoretical three-dimensional structure of the FIV IN catalytic core domain (CCD) was obtained by homology modeling based on a crystal structure of HIV-1 IN CCD. The interaction of the transferred strand of viral DNA with the catalytic cavity of FIV IN was deduced from a crystal structure of a structurally similar transposase complexed with transposable DNA. Molecular docking simulations were conducted using a genetic algorithm (GOLD). Antiviral activity was tested in feline lymphoblastoid MBM cells acutely infected with the FIV Petaluma strain. Circular and total proviral DNA was quantified by real-time PCR. Results The calculated INSTI-binding sites were found to be nearly identical in FIV and HIV-1 IN CCDs. The close similarity of primate and feline lentivirus IN CCDs was also supported by phylogenetic analysis. In line with these bioinformatic analyses, FIV replication was efficiently inhibited in acutely infected cell cultures by three investigational INSTIs, designed for HIV-1 and belonging to different classes. Of note, the naphthyridine carboxamide INSTI, L-870,810 displayed an EC50 in the low nanomolar range. Inhibition of FIV integration in situ was shown by real-time PCR experiments that revealed accumulation of circular forms of FIV DNA within cells treated with L-870,810. Conclusion We report a drug class (other than nucleosidic reverse transcriptase inhibitors) that is capable of inhibiting FIV replication in vitro. The present study helped establish L-870,810, a compound successfully tested in

  4. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

    PubMed

    Li, Luyuan; Paz, Ana C; Wilky, Breelyn A; Johnson, Britt; Galoian, Karina; Rosenberg, Andrew; Hu, Guozhi; Tinoco, Gabriel; Bodamer, Olaf; Trent, Jonathan C

    2015-01-01

    Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas. PMID:26368816

  5. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells

    PubMed Central

    Li, Luyuan; Paz, Ana C.; Wilky, Breelyn A.; Johnson, Britt; Galoian, Karina; Rosenberg, Andrew; Hu, Guozhi; Tinoco, Gabriel; Bodamer, Olaf; Trent, Jonathan C.

    2015-01-01

    Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas. PMID:26368816

  6. Transgenic expression of walleye dermal sarcoma virus rv-cyclin gene in zebrafish and its suppressive effect on liver tumor development after carcinogen treatment.

    PubMed

    Zhan, Huiqing; Spitsbergen, Jan M; Qing, Wei; Wu, Yi Lian; Paul, Thomas A; Casey, James W; Her, Guor Muor; Gong, Zhiyuan

    2010-11-01

    A retrovirus homologue gene of cellular cyclin D₁, walleye dermal sarcoma virus rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish under the control of liver fatty acid-binding protein (lfabp) promoter. To prevent possible fatality caused by overexpression of the oncogene, the GAL4/upstream activation sequence (GAL4/UAS) system was used to maintain the transgenic lines. Thus, both GAL4-activator [Tg(lfabp:GAL4)] and UAS-effector [Tg(UAS:rvcyclin)] lines were generated, and the rv-cyclin gene was activated in the liver after crossing these two lines. Since no obvious neoplasia phenotypes were observed in the double-transgenic line, cancer susceptibility of the transgenic fish expressing rv-cyclin was tested by carcinogen treatment. Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) were more resistant to the carcinogen than siblings not expressing this gene (rvcyclin-). Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ than in rvcyclin- fish, and the liver tumors in the rvcyclin+ group appeared later and were less malignant. These results suggest that expression of rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy. These findings indicate that transgenic fish models are powerful systems for investigating mechanisms of inhibition and regression of liver tumors. PMID:20052603

  7. Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats.

    PubMed

    Netland, I A; Førde, H E; Sleire, L; Leiss, L; Rahman, M A; Skeie, B S; Miletic, H; Enger, P Ø; Goplen, D

    2016-08-01

    Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90 % of all GBMs harbour a deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility and survival. Thus, PI3K represents a potential target for molecular therapy in GBM. We investigated the anti-tumour efficacy of the PI3K inhibitor buparlisib (NVP-BKM120) in GBM cell lines in vitro and in vivo, when treatment was initiated after MRI-confirmed tumour engraftment. We found that buparlisib inhibited glioma cell proliferation in a dose dependent manner, demonstrated by MTS assay, manual cell count and BrdU incorporation. A dose dependent increase in apoptosis was observed through flow cytometric analysis. Furthermore, by immunocytochemistry and western blot, we found a dose dependent inhibition of Akt phosphorylation. Moreover, buparlisib prolonged survival of nude rats harboring human GBM xenografts in three independent studies and reduced the tumours' volumetric increase, as determined by MRI. In addition, histological analyses of xenograft rat brains showed necrotic areas and change in tumour cell nuclei in buparlisib-treated animals. The rats receiving buparlisib maintained their weight, activity level and food- and water intake. In conclusion, buparlisib effectively inhibits glioma cell proliferation in vitro and growth of human GBM xenografts in nude rats. Moreover, the compound is well tolerated when administered at doses providing anti-tumour efficacy. Thus, buparlisib may have a future role in glioma therapy, and further studies are warranted to validate this compound for human use. PMID:27283525

  8. Cough suppression disorders spectrum.

    PubMed

    Reich, Jerome M

    2014-02-01

    Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome. PMID:24462261

  9. 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

  10. 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.

  11. Treatment

    MedlinePlus

    ... Prevention Treatment 2003 U.S. Outbreak African Rodent Importation Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox ... Examining Animals with Suspected Monkeypox African Rodent Importation Ban Resources Related Links Poxvirus Molluscum Contagiosum Orf Virus ( ...

  12. 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.

  13. Photoimmune suppression and photocarcinogenesis.

    PubMed

    Ullrich, Stephen E

    2002-03-01

    The primary cause of non-melanoma skin cancer, the most prevalent form of human neoplasia, is the ultraviolet (UV) radiation found in sunlight. Exposing mice to UV radiation induces skin cancers that are highly antigenic. Upon transfer of an UV-induced skin cancer to a normal syngeneic mouse, the tumor cells are recognized and rapidly destroyed by the immune system of the recipient. This raises the question of how these cancers avoided immune destruction during their development in the UV-irradiated host. This question was answered when it was discovered that in addition to being carcinogenic, UV radiation was also immunosuppressive. Studies with immune suppressed transplantation recipients, and biopsy proven skin cancer patients have confirmed that UV-induced immune suppression is a risk factor for skin cancer development in humans. It is of great importance, therefore, to understand the mechanisms underlying UV-induced immune suppression. The focus of this manuscript will be to use some examples from the more recent scientific literature to review the mechanisms by which UV radiation suppresses the immune response and allows for the progressive outgrowth of antigenic skin tumors. PMID:11861222

  14. Parasitic suppressing circuit

    NASA Technical Reports Server (NTRS)

    Fowler, J. T.; Raposa, F. L. (Inventor)

    1973-01-01

    A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is also connected across the inductor and to the switch means to automatically render the switch means conducting when inductive current through the inductor ceases to flow.

  15. Monotherapy with lopinavir/ritonavir versus standard of care in HIV-infected patients virologically suppressed while on treatment with protease inhibitor-based regimens: results from the MoLo study.

    PubMed

    Gianotti, Nicola; Poli, Andrea; Galli, Massimo; Pan, Angelo; Rizzardini, Giuliano; Soria, Alessandro; Viale, Pierluigi; Di Biagio, Antonio; Quirino, Tiziana; Viganò, Paolo; Bonfanti, Paolo; d'Arminio Monforte, Antonella; Fortino, Ida; Lazzarin, Adriano

    2014-10-01

    This study compared the cost-efficacy ratios of lopinavir/ritonavir monotherapy (LPV/r-MT) and of standard of care in virologically suppressed HIV-infected patients. The results of the efficacy and safety analyses are presented. We conducted a multicentre, randomised, open-label trial of HIV-infected adults on stable treatment, with HIV- RNA <50 copies/mL, randomised to continue the ongoing regimen (cART-arm) or to switch to LPV/r (400/100 mg BID) MT (MT-arm). Time to virological rebound (VR = confirmed HIV-RNA ?50 copies/mL) was estimated by Ka- plan-Meier method and changes in laboratory values during follow-up were evaluated by univariate mixed-linear models. Ninety-four patients were randomised and analysed (43 in the MT-arm and 51 in the cART-arm). Five (four in the MT and 1 in the cART-arm; p=0.175) had VR, but time to VR did not statistically differ between the two arms (p=0.143). Major PI mutations were not detected at VR. Patients on MT had significant increases in total choles- terol [difference in mean change between MT and cART arm: 0.77 (±0.30) mg/dL per month; p=0.012] and eGFR [difference in mean change between MT and cART arm: 0.24 (±0.11) mL/min/1.73 m2 per month; p=0.029]. LPV/r-MT seems safe in most patients and should be considered in patients who have developed kidney toxicity from tenofovir. PMID:25387282

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Vibrotactile suppression of tinnitus

    NASA Astrophysics Data System (ADS)

    Lenhardt, Martin L.

    2002-05-01

    At the Society's 142nd meeting, the efficacy of high frequency bone conducted stimulation in suppressing tinnitus was presented. The hypothesized mechanism was the reprogramming of frequency tuning of auditory neurons in the central nervous system, secondarily to peripheral hearing loss. This mechanism is unlikely in cases of tinnitus in the presence of normal audiometric sensitivity. There is the possibility that hearing loss above 10 kHz can play a role in tinnitus, an association not thoroughly explored. Somatomotor stimulation influencing the quality of tinnitus has been reported, as have interconnections of the auditory and somatosensory systems. There would appear to be an evolutionary advantage of linking the sensorimotor organization of the external ear and the auditory function of the brainstem in sound localization. Thus, stimulation of the pinna and post auricular area may be a means of suppressing tinnitus. To that end a thin aluminum ceramic bimorph was constructed to fit on the inner surface of the pinna. When driven by low (<100 Hz) and high (>10 kHz) frequencies multiplied by MHz carriers, demodulation in the skin resulted in vibrotactile stimulation. Tactile stimulation was an adjunct to the high frequencies resulting in a multimodal suppressive effect in a small pilot study.

  1. Menstrual suppression: current perspectives

    PubMed Central

    Hillard, Paula Adams

    2014-01-01

    Menstrual suppression to provide relief of menstrual-related symptoms or to manage medical conditions associated with menstrual morbidity or menstrual exacerbation has been used clinically since the development of steroid hormonal therapies. Options range from the extended or continuous use of combined hormonal oral contraceptives, to the use of combined hormonal patches and rings, progestins given in a variety of formulations from intramuscular injection to oral therapies to intrauterine devices, and other agents such as gonadotropin-releasing hormone (GnRH) antagonists. The agents used for menstrual suppression have variable rates of success in inducing amenorrhea, but typically have increasing rates of amenorrhea over time. Therapy may be limited by side effects, most commonly irregular, unscheduled bleeding. These therapies can benefit women’s quality of life, and by stabilizing the hormonal milieu, potentially improve the course of underlying medical conditions such as diabetes or a seizure disorder. This review addresses situations in which menstrual suppression may be of benefit, and lists options which have been successful in inducing medical amenorrhea. PMID:25018654

  2. Next generation fire suppressants

    SciTech Connect

    Brown, J.A.

    1995-03-01

    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 band microprocessor 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. 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.

  4. Suppression of flutter

    NASA Technical Reports Server (NTRS)

    Nissim, E. (Inventor)

    1973-01-01

    An active aerodynamic control system to control flutter over a large range of oscillatory frequencies is described. The system is not affected by mass, stiffness, elastic axis, or center of gravity location of the system, mode of vibration, or Mach number. The system consists of one or more pairs of leading edge and trailing edge hinged or deformable control surfaces, each pair operated in concert by a stability augmentation system. Torsion and bending motions are sensed and converted by the stability augmentation system into leading and trailing edge control surface deflections which produce lift forces and pitching moments to suppress flutter.

  5. Planck-suppressed operators

    SciTech Connect

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam E-mail: dbaumann@damtp.cam.ac.uk E-mail: mcallister@cornell.edu

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10{sup 5}H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10{sup 2}H.

  6. Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis

    PubMed Central

    Hwang, J.K.; Erkhembaatar, M.; Gu, D.R.; Lee, S.H.; Lee, C.H.; Shin, D.M.; Lee, Y.R.; Kim, M.S.

    2014-01-01

    Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca2+ ([Ca2+]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca2+]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow–derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca2+]i while suppressing RANKL-induced [Ca2+]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca2+]i was dependent on extracellular Ca2+ and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca2+ channels (VGCCs), but was independent of store-operated Ca2+ channels. Notably, after transient [Ca2+] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca2+]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. PMID:24850617

  7. Suppression of ras-transformants (review).

    PubMed

    Kuzumaki, N

    1991-01-01

    Transforming ras genes are the oncogenes most frequently identified in human cancers. This justifies the intense interest in finding ways to suppress oncogenicity in these gene family-mediated transformants. The methods of suppression can be classified as 1) genetical, 2) biological and 3) pharmacological. Most of the reagents used for the suppression inhibit rodent transformants induced by transfected viral or activated cellular ras oncogenes, but some of the reagents are also effective when applied to natural human transformants that contain activated ras oncogenes. The growth and tumorigenicity of the ras-transformants are suppressed by the inhibition of the integration, transcription, translation or post-translational modification of the ras genes and p21 ras proteins, as well as the inhibition of the expression of genes which collaborate in the ras-transformation or the enhancement of some tumor suppressor genes. These observations offer novel approaches to the investigation of malignant transformation by ras-oncogenes, and have potential application in treatment of ras-oncogene-induced tumors. PMID:2018365

  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. 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.

  10. Interference suppression of SRS

    SciTech Connect

    Kochanov, V P

    2011-01-24

    The theory of three-wave SRS is developed, which takes into account nonlinear dispersion of a medium for arbitrary phases of the pump waves at the input to the medium. The effect of interference suppression of SRS is predicted for values of the total phase of the three-wave pump (2n+1){pi} (n=0, {+-}1, {+-}2...), the effect being caused by the destructive interference of polarisations of the nonresonant dipole-allowed transitions. The relation between the contributions of the linear and nonlinear dispersions to the SRS is found. It is shown that at a sufficiently large wave detuning, the anti-Stokes wave amplitude experiences spatial oscillations. (nonlinear-optics phenomena)

  11. 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.

  12. 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.

  13. 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. PMID:26924682

  14. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  15. MEK5 suppresses osteoblastic differentiation.

    PubMed

    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. PMID:25998381

  16. HIV-1 Reservoirs During Suppressive Therapy.

    PubMed

    Barton, Kirston; Winckelmann, Anni; Palmer, Sarah

    2016-05-01

    The introduction of antiretroviral therapy (ART) 20 years ago has dramatically reduced morbidity and mortality associated with HIV-1. Initially there was hope that ART would be curative, but it quickly became clear that even though ART was able to restore CD4(+) T cell counts and suppress viral loads below levels of detection, discontinuation of treatment resulted in a rapid rebound of infection. This is due to persistence of a small reservoir of latently infected cells with a long half-life, which necessitates life-long ART. Over the past few years, significant progress has been made in defining and characterizing the latent reservoir of HIV-1, and here we review how understanding the latent reservoir during suppressive therapy will lead to significant advances in curative approaches for HIV-1. PMID:26875617

  17. 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.

  18. 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.

  19. Nonanesthetics can suppress learning.

    PubMed

    Kandel, L; Chortkoff, B S; Sonner, J; Laster, M J; Eger, E I

    1996-02-01

    Nonanesthetic gases or vapors do not abolish movement in response to noxious stimuli despite partial pressures and affinities for lipids that would, according to the Meyer-Overton hypothesis, predict such abolition. We investigated whether nonanesthetics depress learning and memory (i.e., provide amnesia). To define learning, we used a "fear-potentiated startle paradigm": rats trained to associate light with a noxious stimulus (footshock) will startle more, as measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise) is paired with light than when the startle-eliciting stimulus is presented alone. We imposed light-shock pairings on 98 rats under three conditions: no anesthesia (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic concentration (MAC) of desflurane; or two nonanesthetics (1,2-dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a dose-related depression of learning with abolition of learning at 0.28 MAC. Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane. 1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning. Because nonanesthetics suppress learning but not movement (the two critical components of anesthesia), they may prove useful in discriminating between mechanisms and sites of action of anesthetics. PMID:8561335

  20. 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. PMID:17909897

  1. Inducing amnesia through systemic suppression.

    PubMed

    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

  2. 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

  3. Sound can suppress visual perception.

    PubMed

    Hidaka, Souta; Ide, Masakazu

    2015-01-01

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs. PMID:26023877

  4. Photoperiodic Suppression of Drug Reinstatement

    PubMed Central

    Sorg, Barbara A.; Stark, Gemaine; Sergeeva, Anna; Jansen, Heiko T.

    2011-01-01

    The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our

  5. Suppression of experimental allergic encephalomyelitis by 15-deoxyspergualin.

    PubMed

    Yamamura, T; Da-Lin, Y; Satoh, J; Tabira, T

    1987-12-01

    15-Deoxyspergualin (DSG), a novel antitumor antibiotic, was tested for treatment of acute experimental allergic encephalomyelitis (EAE) in Lewis rats. Clinical and histologic signs of EAE by active sensitization with myelin basic protein were profoundly inhibited by prophylactic administration of DSG in a dose-dependent manner. By the treatment during the inductive phase, the onset of EAE was significantly delayed. Antigen-specific proliferation of lymph node cells and the ability of spleen cells to transfer EAE were suppressed but concanavalin A-induced lymphocyte proliferation was not altered. Passive EAE induced with an encephalitogenic T cell line was also prevented by DSG-treatment, although DSG did not suppress but rather augmented the activation of T cells in vitro. Taken together, DSG is not a non-specific lymphocyte toxin but a unique immunomodulator that can suppress both inductive and effector phases of EAE. PMID:3502003

  6. 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.

  7. Selenite suppression of cadmium-induced testicular apoptosis.

    PubMed

    Jones, M M; Xu, C; Ladd, P A

    1997-01-15

    The characteristic apoptotic ladder-like patterns of rat testicular DNA on agarose gel electrophoresis which results from treatment with CdCl2 are suppressed by the administration of Na2SeO3. The examination of testicular tissue using an ELISA programmed cell death detection procedure confirmed this selenite suppression of cadmium-induced apoptosis. The administration of the Na2SeO3 at either 0.5, 1, 2 h prior to or 0.5, 1, 2 h after the administration of the CdCl2 appear to be almost equally effective at suppressing the apoptotic response. These results are in accord with previous studies on the Na2SeO3 suppression of cadmium induced necrotic changes in tissues and suggest that Na2SeO3 interferes with both necrosis and apoptosis. PMID:9020518

  8. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  9. 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

  10. 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

  11. Neurotropin Suppresses Inflammatory Cytokine Expression and Cell Death through Suppression of NF-κB and JNK in Hepatocytes

    PubMed Central

    Zhang, Bi; Roh, Yoon Seok; Liang, Shuang; Liu, Cheng; Naiki, Mitsuru; Masuda, Koichi; Seki, Ekihiro

    2014-01-01

    Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part. PMID:25470242

  12. Suppression of fertility in adult dogs.

    PubMed

    Maenhoudt, C; Santos, N R; Fontbonne, A

    2014-06-01

    Unfortunately, the overpopulation of dogs is still a problem in the majority of countries and even though surgical methods of sterilization, the most traditional and commonly used technique, have been intensively performed, the impact on the dog population is negligible. The neutering of companion animals as ovariohysterectomy (spaying) or orchidectomy (castration) has its limitations because of the cost, the need of a surgical environment and the risk of surgical and/or anaesthetical complications (ACCD 2009). In fact, surgical castration has been banished in some northern European countries and has limited acceptance in other countries. In a survey performed in Sao Paulo, Brazil, 56.5% of the owners of adopted shelter dogs were against the surgical procedure for different reasons (Soto et al. 2005). Currently, the options for contraception, defined as suppression of fertility are based on hormonal treatment. The treatments can be divided into analogues of gonadotropin releasing hormone (GnRH), progestins and androgens. Other possibilities of contraception are via the immunological system with vaccinations against GnRH, the luteinizing hormone (LH) receptor and the zona pellucida proteins. Finally, there is also the intra-epididymal or intratesticular injection of sclerosing substances in dogs. Mechanical devices to disrupt fertility are not used anymore due to the side effects. Suppression of fertility in adult dogs will be reviewed in order of use and possible impact on the dog population. PMID:24947862

  13. Cilostazol suppresses angiotensin II-induced apoptosis in endothelial cells

    PubMed Central

    SHI, MIAO-QIAN; SU, FEI-FEI; XU, XUAN; LIU, XIONG-TAO; WANG, HONG-TAO; ZHANG, WEI; LI, XUE; LIAN, CHENG; ZHENG, QIANG-SUN; FENG, ZHI-CHUN

    2016-01-01

    Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase-3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII-induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII-induced p-Akt downregulation and cleaved caspase-3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII-induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII-induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway. PMID:26862035

  14. 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. PMID:15055225

  15. 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

  16. Vibration suppression using smart structures

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    1991-01-01

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  17. Background suppression in MAS NMR

    NASA Astrophysics Data System (ADS)

    White, Jeffery L.; Beck, Larry W.; Ferguson, David B.; Haw, James F.

    Pulse sequences for suppressing background signals from spinning modules used in magic-angle spinning NMR are described. These pulse sequences are based on spatially selective composite 90° pulses originally reported by Bax, which provide for no net excitation of spins outside the homogeneous region of the coil. We have achieved essentially complete suppression of background signals originating from our Vespel spinning module (which uses a free-standing coil) in both 1H and 13C spectra without notable loss in signal intensity. Successful modification of both Bloch decay and cross-polarization pulse sequences to include spatially selective pulses was essential to acquire background-free spectra for weak samples. Background suppression was also found to be particularly valuable for both T1 and T1 ϱ, relaxation measurements.

  18. Aging and repeated thought suppression success.

    PubMed

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  19. 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.

  20. 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. PMID:25961580

  1. 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

  2. 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.

  3. The Evolution of Alpha-Blockers for the Treatment of Benign Prostatic Hyperplasia

    PubMed Central

    Lepor, Herbert

    2006-01-01

    Alpha-blockers have been evaluated for the treatment of benign prostatic hyperplasia (BPH) for 30 years, from early trials with the nonselective α-inhibitor phenoxybenzamine to short-acting (prazosin) then long-acting (terazosin, doxazosin, tamsulosin, alfuzosin) selective α1-antagonists. All of the α-blockers evaluated have demonstrated comparable effectiveness, and the evolution of α-blocker therapy for BPH has therefore focused primarily on improving convenience and tolerability. Although all of the long-acting α1-blockers are well tolerated, only tamsulosin and alfuzosin SR are administered without the requirement for dose titration. Alfuzosin has the additional advantage over tamsulosin of a lower incidence of ejaculatory dysfunction. Studies of subtype-selective α1-antagonists have not demonstrated superior efficacy or improved tolerability over the existing long-acting α1-blockers. PMID:17215999

  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. 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.

  6. Leuprolide acetate suppresses pedophilic urges and arousability.

    PubMed

    Schober, Justine M; Kuhn, Phyllis J; Kovacs, Paul G; Earle, James H; Byrne, Peter M; Fries, Ruth A

    2005-12-01

    Cognitive-behavioral psychotherapy was compared with cognitive-behavioral psychotherapy augmented by leuprolide acetate (LA) for suppression of pedophilic behavior. Five male pedophiles (M age, 50 years; range, 36-58) were administered LA by Depo injection for 12 months, followed by saline placebo for 12 months. Testosterone levels, sexual interest preference by visual reaction time (Abel Assessment), penile tumescence (Monarch Penile Plethysmography, PPG), as well as strong sexual urges toward children and masturbatory frequency involving thoughts of children (polygraph), were measured every 3 months. On LA, testosterone decreased to castrate levels. Penile tumescence was significantly suppressed compared with baseline, but sufficient response remained to detect pedophilic interest. Pedophilic interest was also detected by visual reaction times. When asked about having pedophilic urges and masturbating to thoughts of children, all subjects self-reported a decrease. Polygraph responses indicated subjects were not deceptive. On placebo, testosterone and physiologic arousal eventually rose to baseline. As noted by polygraph, at baseline and on placebo, subjects were deceptive regarding increased pedophilic urges and masturbatory frequency. Interest preference, as measured by Abel Assessment and Monarch PPG, was generally unchanged throughout the study. Cognitive-behavioral psychotherapy augmented with LA significantly reduced pedophilic fantasies, urges, and masturbation; however, pedophilic interest did not change during 1 year of therapy. Deceptive responses by polygraph suggested that self-report was unreliable. Follow-up utilizing objective measures is essential for monitoring efficacy of treatment in pedophilia. Our study supports the premise that suppression of pedophilic behavior is possible. LA may augment cognitive-behavioral psychotherapy and help break the sequence leading to a re-offense. PMID:16362253

  7. Suppressing explosive synchronization by contrarians

    NASA Astrophysics Data System (ADS)

    Zhang, Xiyun; Guan, Shuguang; Zou, Yong; Chen, Xiaosong; Liu, Zonghua

    2016-01-01

    Explosive synchronization (ES) has recently received increasing attention and studies have mainly focused on the conditions of its onset so far. However, its inverse problem, i.e. the suppression of ES, has not been systematically studied so far. As ES is usually considered to be harmful in certain circumstances such as the cascading failure of power grids and epileptic seizure, etc., its suppression is definitely important and deserves to be studied. We here study this inverse problem by presenting an efficient approach to suppress ES from a first-order to second-order transition, without changing the intrinsic network structure. We find that ES can be suppressed by only changing a small fraction of oscillators into contrarians with negative couplings and the critical fraction for the transition from the first order to the second order increases with both the network size and the average degree. A brief theory is presented to explain the underlying mechanism. This finding underlines the importance of our method to improve the understanding of neural interactions underlying cognitive processes.

  8. Stimulus Fractionation by Interocular Suppression

    PubMed Central

    Zadbood, Asieh; Lee, Sang-Hun; Blake, Randolph

    2011-01-01

    Can human observers distinguish physical removal of a visible stimulus from phenomenal suppression of that stimulus during binocular rivalry? As so often happens, simple questions produce complex answers, and that is the case in the study reported here. Using continuous flash suppression to produce binocular rivalry, we were able to identify stimulus conditions where most – but not all – people utterly fail to distinguish physical from phenomenal stimulus removal, although we can be certain that those two equivalent perceptual states are accompanied by distinct neural events. More interestingly, we find subtle variants of the task where distinguishing the two states is trivially easy, even for people who utterly fail under the original conditions. We found that stimulus features are differentially vulnerable to suppression. Observers are able to be aware of existence/removal of some stimulus attributes (flicker) but not others (orientation), implying that interocular suppression breaks down the unitary awareness of integrated features belonging to a visual object. These findings raise questions about the unitary nature of awareness and, also, place qualifications on the utility of binocular rivalry as a tool for studying the neural concomitants of conscious visual awareness. PMID:22102839

  9. Charmonium suppression in nuclear collisions

    SciTech Connect

    Gavin, S. |

    1996-11-01

    Measurements of {psi} and {psi}{prime} production from experiment NA50 at the CERN SPS are compared to calculations based on a hadronic model of charmonium suppression developed previously. Data on centrality dependence and total cross sections are in good accord with these predictions. Uncertainties in theoretical quantities such as NA50`s L parameter are discussed.

  10. 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.

  11. DENDRITIC POLYMERS AS FIRE SUPPRESSANTS

    EPA Science Inventory

    This report describes an evaluation of the applicability of one of the latest advances in polymer technology (dendritic polymers) to suppressing fires, one of the greatest survivability threats to military personnel and vehicles. Certain types of alkali and transition metal compl...

  12. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  13. High temperature suppression of dioxins.

    PubMed

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants. PMID:26716881

  14. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    PubMed Central

    Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi

    2013-01-01

    Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication. PMID:23698397

  15. Suppression of coronavirus replication by cyclophilin inhibitors.

    PubMed

    Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi

    2013-05-01

    Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication. PMID:23698397

  16. 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

  17. [Suppression of sexual activity and reproduction in male small ruminants].

    PubMed

    Mihsler, Lisa; Wagner, Henrik; Wehrend, Axel

    2016-06-16

    Handling and husbandry of male small ruminants after sexual maturity often become difficult. Castration is currently the most reliable solution to this problem. Medicinal procedures for temporary inhibition of the gonad function could provide an alternative. Following a short overview of surgical castration, the current knowledge on the application of vaccines against gonadotropin-releasing hormone (GnRH) and GnRH agonist in rams and billy goats is presented in a literature overview. In rams, GnRH vaccination has been used successfully for temporary suppression of the reproduction function, regardless of an animal's age at the time of therapy initiation. Fewer investigations are available for the billy goat. A complete suppression of spermatogenesis was not achieved in all cases. Currently, treatment with GnRH agonists does not represent a relible method for the suppression of gonad function. PMID:27189125

  18. 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

  19. Suppression of Drug Resistance in Dengue Virus

    PubMed Central

    Mateo, Roberto; Nagamine, Claude M.

    2015-01-01

    ABSTRACT Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of “dominant drug targets,” in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection. PMID:26670386

  20. Fever: suppress or let it ride?

    PubMed

    Ray, Juliet J; Schulman, Carl I

    2015-12-01

    While our ability to detect and manage fever has evolved since its conceptualization in the 5(th) century BC, controversy remains over the best evidence-based practices regarding if and when to treat this physiologic derangement in the critically ill. There are two basic fields of thought: (I) fever should be suppressed because its metabolic costs outweigh its potential physiologic benefit in an already stressed host; vs. (II) fever is a protective adaptive response that should be allowed to run its course under most circumstances. The latter approach, sometime referred to as the "let it ride" philosophy, has been supported by several recent randomized controlled trials like that of Young et al. [2015], which are challenging earlier observational studies and may be pushing the pendulum away from the Pavlovian treatment response. PMID:26793378

  1. Fever: suppress or let it ride?

    PubMed Central

    Ray, Juliet J.

    2015-01-01

    While our ability to detect and manage fever has evolved since its conceptualization in the 5th century BC, controversy remains over the best evidence-based practices regarding if and when to treat this physiologic derangement in the critically ill. There are two basic fields of thought: (I) fever should be suppressed because its metabolic costs outweigh its potential physiologic benefit in an already stressed host; vs. (II) fever is a protective adaptive response that should be allowed to run its course under most circumstances. The latter approach, sometime referred to as the “let it ride” philosophy, has been supported by several recent randomized controlled trials like that of Young et al. [2015], which are challenging earlier observational studies and may be pushing the pendulum away from the Pavlovian treatment response. PMID:26793378

  2. 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.

  3. 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.

  4. Non-Antidepressant Long-Term Treatment in Post-Traumatic Stress Disorder (PTSD).

    PubMed

    Kerbage, Hala; Richa, Sami

    2013-02-01

    Introduction: Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. Methods: We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Results: Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Discussion: Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack

  5. 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 Central

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

    2013-01-01

    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 80-100 nM. 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. PMID:23153524

  6. Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution.

    PubMed

    Basha, Riyaz; Connelly, Sarah F; Sankpal, Umesh T; Nagaraju, Ganji Purnachandra; Patel, Hassaan; Vishwanatha, Jamboor K; Shelake, Sagar; Tabor-Simecka, Leslie; Shoji, Mamoru; Simecka, Jerry W; El-Rayes, Bassel

    2016-05-01

    Combination of dietary/herbal spice curcumin (Cur) and COX inhibitors has been tested for improving therapeutic efficacy in pancreatic cancer (PC). The objective of this study was to identify agent with low toxicity and COX-independent mechanism to induce PC cell growth inhibition when used along with Cur. Anticancer NSAID, tolfenamic acid (TA) and Cur combination were evaluated using PC cell lines. L3.6pl and MIA PaCa-2 cells were treated with Cur (5-25μM) or TA (25-100μM) or combination of Cur (7.5μM) and TA (50μM). Cell viability was measured at 24-72h posttreatment using CellTiter-Glo kit. While both agents showed a steady/consistent effect, Cur+TA caused higher growth inhibition. Antiproliferative effect was compared with COX inhibitors, Ibuprofen and Celebrex. Cardiotoxicity was assessed using cordiomyocytes (H9C2). The expression of Sp proteins, survivin and apoptotic markers (western blot), caspase 3/7 (caspase-Glo kit), Annexin-V staining (flow cytometry), reactive oxygen species (ROS) and cell cycle phase distribution (flow cytometry) was measured. Cells were treated with TNF-α, and NF-kB translocation from cytoplasm to nucleus was evaluated (immunofluorescence). When compared to individual agents, combination of Cur+TA caused significant increase in apoptotic markers, ROS levels and inhibited NF-kB translocation to nucleus. TA caused cell cycle arrest in G0/G1, and the combination treatment showed mostly DNA synthesis phase arrest. These results suggest that combination of Cur+TA is less toxic and effectively enhance the therapeutic efficacy in PC cells via COX-independent mechanisms. PMID:27133426

  7. 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. PMID:20726290

  8. A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice

    PubMed Central

    Kozy, Heather M.; Lum, Jeremy A.; Sweetwood, Rosemary; Chu, Mabel; Cunningham, Cameron R.; Salamon, Hugh; Lloyd, Clare M.; Coffman, Robert L.; Hessel, Edith M.

    2015-01-01

    Background CpG-containing oligodeoxynucleotides (CpG-ODN) are potent inhibitors of Th2-mediated allergic airway disease in sensitized mice challenged with allergen. A single treatment has transient effects but a limited series of treatments has potential to achieve clinically meaningful sustained inhibition of allergic airway disease. Objective To optimize the treatment regimen and determine the mechanisms of action in mice of an inhaled form of CpG-ODN being developed for human asthma treatment. Methods A limited series of weekly intranasal 1018 ISS (CpG-ODN; B-class) treatments were given to ragweed allergen-sensitized mice chronically exposed to allergen during and after the 1018 ISS treatment regimen. Treatment effects were evaluated by measuring effect on lung Th2 cytokines and eosinophilia as well as lung dendritic cell function and T cell responses. Results Twelve intranasal 1018 ISS treatments induced significant suppression of BAL eosinophilia and IL-4, IL-5, and IL-13 levels and suppression was maintained through 13 weekly ragweed exposures administered after treatment cessation. At least 5 treatments were required for lasting Th2 suppression. CpG-ODN induced moderate Th1 responses but Th2 suppression did not require IFN-γ. Th2 suppression was associated with induction of a regulatory T cell response. Conclusion A short series of CpG-ODN treatments results in sustained suppression of allergic lung inflammation induced by a clinically relevant allergen. PMID:24464743

  9. Adrenocortical suppression in cats given megestrol acetate.

    PubMed

    Chastain, C B; Graham, C L; Nichols, C E

    1981-12-01

    Megestrol acetate was given orally to 8 cats at a dose of 2.5 mg every other day for 2 weeks and to 8 cats at a dose of 5.0 mg every day for 2 weeks. Four cats were designated nontreated controls. Pre-ACTH-stimulated plasma concentrations of cortisol (hydrocortisone) and ACTH-stimulated cortisol and tolerance to large-dose glucose infusion (IV) were determined on each of the 20 cats given megestrol acetate. Cats were restrained with acepromazine maleate and ketamine hydrochloride during blood sample collection and large-dose glucose infusion. Adrenocortical function and tolerance to large-dose glucose infusion were reevaluated for 4 weeks--after 1st and 2nd weeks of megestrol acetate treatment of the treated groups, and after 1st and 2nd weeks when treatment was stopped (ie, experiment weeks 3 and 4). Each week a cat from the control group and 2 cats from the 2 treated groups were selected to determine the changes occurring during the experiment for that week; after collection of plasma samples, each week's 5 selected cats were euthanatized and necropsied. Significant impairment of adrenocortical function and alteration of adrenocortical morphology occurred with both treated groups. The most severe adrenocortical alterations occurred in the cats 1 week after megestrol acetate was no longer given (ie, experiment week 3). Megestrol acetate-induced adrenocortical suppression contributed to the death of 1 cat. It was concluded that if stress occurs to cats on treatment or soon after treatment with megestrol acetate, glucocorticoids should be supplemented. The effects of megestrol acetate on glucose tolerance were overshadowed by the unforeseen intolerance caused by chemical restraint with acepromazine maleate and ketamine hydrochloride. PMID:6280517

  10. Dimethyl fumarate suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway.

    PubMed

    Kobayashi, Kunitoshi; Tomiki, Hiroki; Inaba, Yuji; Ichikawa, Motoki; Kim, Byung S; Koh, Chang-Sung

    2015-07-01

    Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A. PMID:25721871