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Sample records for acute fluoxetine treatment

  1. Effects of acute and subchronic treatments with fluoxetine and desipramine on the memory of fear in moderate and high-intensity contextual conditioning.

    PubMed

    Santos, Julia M; Martinez, Raquel C R; Brandão, Marcus L

    2006-08-07

    Selective serotonin and noradrenalin reuptake inhibitors such as fluoxetine and desipramine, respectively, are efficacious in the treatment of depression and chronic stress. Although they inhibit the reuptake of the biogenic monoamines soon after administration, therapeutic improvements occur only after 2 or 3 weeks. Freezing response and potentiated startle are common responses to moderate fear contextual conditioning. However, freezing but not startle is increased in rats that undergo intense fear conditioning. In this study, we evaluated the effects of acute and subchronic administration of fluoxetine and desipramine on these responses in testing sessions, as indices of fear in moderate and high fear conditioning. Fluoxetine did not show any significant effect on the moderate fear conditioning but reduced freezing and restored the startle response in rats under intense fear conditioning. In comparison, desipramine had no effect on the startle response when administered acutely or subchronically while freezing of the intense fear conditioning was reduced. Our findings indicate that intense contextual fear conditioning is sensitive to subchronic treatment with fluoxetine and resistant to desipramine. Fluoxetine appears to restore the serotoninergic function in brain areas recruited by intense contextual fear conditioning. These effects of fluoxetine may underlie its reported efficacy in the pharmacotherapy of panic disorders.

  2. Behavioral characterization of the alarm reaction and anxiolytic-like effect of acute treatment with fluoxetine in piauçu fish.

    PubMed

    Barbosa Júnior, Augusto; Alves, Fabiana Luca; Pereira, Aparecida de Sousa Fim; Ide, Liliam Midori; Hoffmann, Anette

    2012-02-01

    In Ostariophysan fish, the detection of the alarm substance liberated into the water as a consequence of an attack by a predator elicits an alarm reaction or anti-predatory behavior. In this study, experiments were performed to: (i) describe and quantitatively characterize the behavioral and ventilatory responses in piauçu fish (Leporinus macrocephalus), individually and as part of a school, to conspecific alarm substance (CAS) and; (ii) test the effect of acute fluoxetine treatment on alarm reaction. Histological analysis revealed the presence of club cells in the intermediate and superficial layers of the epidermis. The predominant behavioral response to CAS was freezing for fish held individually, characterized by the cessation of the swimming activity as the animal settles to a bottom corner of the aquarium. Fish exposed to CAS showed decrease in the mean ventilatory frequency (approximately 13%) relative to control. In schools, CAS elicited a biphasic response that was characterized by erratic movements followed by increased school cohesion and immobility, reflected as an increased school cohesion (65.5% vs. -5.8% for controls) and in the number of animals near the bottom of the aquarium (42.0% vs. 6.5% for controls). Animals treated with single i.p. injections of fluoxetine (10 μg/g b.w.) did not exhibit alarm behavior following CAS stimulation. These results show that an alarm pheromone system is present in piauçu fish, evidenced by the presence of epidermal club cells and an alarm reaction induced by CAS and consequently of a chemosensory system to transmit the appropriate information to neural structures responsible for initiating anti-predator behavioral responses. In addition, fluoxetine treatment caused an anxiolytic-like effect following CAS exposure. Thus, the alarm reaction in piauçu can be a useful model for neuroethological and pharmacological studies of anxiety-related states.

  3. Fluoxetine and diazepam acutely modulate stress induced-behavior.

    PubMed

    Giacomini, Ana Cristina V V; Abreu, Murilo S; Giacomini, Luidia V; Siebel, Anna M; Zimerman, Fernanda F; Rambo, Cassiano L; Mocelin, Ricieri; Bonan, Carla D; Piato, Angelo L; Barcellos, Leonardo J G

    2016-01-01

    Drug residue contamination in aquatic ecosystems has been studied extensively, but the behavioral effects exerted by the presence of these drugs are not well known. Here, we investigated the effects of acute stress on anxiety, memory, social interaction, and aggressiveness in zebrafish exposed to fluoxetine and diazepam at concentrations that disrupt the hypothalamic-pituitary-interrenal (HPI) axis. Stress increased the locomotor activity and time spent in the bottom area of the tank (novel tank). Fluoxetine and diazepam prevented these behaviors. We also observed that stress and fluoxetine and diazepam exposures decreased social interaction. Stress also increased aggressive behavior, which was not reversed by fluoxetine or diazepam. These data suggest that the presence of these drugs in aquatic ecosystems causes significant behavioral alterations in fish.

  4. Fluoxetine

    MedlinePlus

    Fluoxetine (Prozac) is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks ( ...

  5. Three cases of paraphilias responsive to fluoxetine treatment.

    PubMed

    Perilstein, R D; Lipper, S; Friedman, L J

    1991-04-01

    Three cases are presented in which fluoxetine was employed in the apparently successful treatment of paraphilia, a disorder which has been difficult to treat pharmacologically. Therapeutic benefit may have been related to the efficacy of fluoxetine in the treatment of obsessive compulsive disorders or to direct effects on sexual activity, or both.

  6. Subchronic treatment with fluoxetine attenuates the proerectile effect of Aspidosperma ulei Markgr (Apocyanaceae)

    PubMed Central

    Campos, Adriana Rolim; de Andrade Uchôa, Daniel Esdras; Rocha, Edilberto Silveira; Martins da Costa, José Galberto; Rao, Vietla Satyanarayana

    2011-01-01

    Objective: To evaluate the ability of acute or chronic treatment with fluoxetine to alter the proerectile effect of Aspidosperma ulei alkaloid-rich fraction (F3-5). Materials and Methods: In the first series of experiments, three groups of mice received either a single intraperitoneal injection of vehicle, F3-5 (25 mg/kg) or fluoxetine (10 mg/kg) + F3-5. Three behavioral responses were counted over a period of 30 min: erection, erection-like response and genital grooming. In a second series of experiments, animals treated for 13 days with fluoxetine or fluoxetine + F3-5 were assessed. Results: A. ulei has been suggested to have proerectile effect in mice. Subchronic (13-d) treatment with fluoxetine resulted in a reduction in the number erections in F3-5-treated mice. Conclusion: Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapy. Acute administration of fluoxetine resulted in a near total reversal of the proerectile effect of F3-5. PMID:22144779

  7. Predictors of an acute antidepressant response to fluoxetine and sertraline.

    PubMed

    Flament, M F; Lane, R M; Zhu, R; Ying, Z

    1999-09-01

    Sertraline and fluoxetine have different pharmacologic and pharmacokinetic profiles which may be of clinical relevance in the determination of response in different subtypes of depression. A randomized, double-blind, 6-week study comparing sertraline (50-100 mg/day) with fluoxetine (20-40 mg/day) in 286 outpatients with major depression, who had demonstrated comparable efficacy and tolerability for the two drugs, was analysed by subgroups of patients at baseline with melancholia, severe depression, single depressive episode, multiple depressive episodes, high anxiety, low anxiety, psychomotor retardation and psychomotor agitation. Multiple logistic regression with regressors including treatment-by-subgroup variables revealed that, within certain subgroups, the efficacy might differ substantially from that of the whole treatment group. However, the only treatment-by-subgroup interaction term that was significant was anxiety (P < 0.05). There was no evidence of interaction in single or recurrent episode subgroups, and these were not included in subsequent analyses. Subsequent two-sample statistical comparison tests of response (i.e. Hamilton Depression Scale reduction > or = 50%) rates at study endpoint between treatment groups demonstrated that patients with melancholic depression and those with symptoms of psychomotor agitation yielded a significantly greater proportion of responders with sertraline compared to fluoxetine (P < 0.05). Response rates in sertraline- and fluoxetine-treated patients, respectively, were: overall study 59%, 51%; melancholia 59%, 44%; severe depression 59%, 41%; low anxiety 71%, 55%; high anxiety 47%, 48%; psychomotor retardation, 48%, 46%; and psychomotor agitation 62%, 39%. Multiple logistic regression adjusting for possible confounding factors, that included a treatment by anxiety interaction term, also led to similar findings. In particular, the analysis showed that significant differences existed in favour of sertraline in patients

  8. Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression: a clinical study.

    PubMed

    Fabre, L F; Scharf, M B; Itil, T M

    1991-06-01

    The safety and efficacy of nortriptyline and fluoxetine were compared in a double-blind, randomized, multicenter 5-week trial involving 205 outpatients with acute major depression of moderate severity. Seventy-two nortriptyline and 84 fluoxetine patients completed at least 2 weeks of medication and were included in the efficacy analysis; all patients were evaluated for side effects. Average total scores on the Hamilton Rating Scale for Depression (HAM-D) for both treatment groups declined from 22-23 at baseline to 11.5 at the conclusion of the 5-week period. At Week, 5, 71% of nortriptyline patients and 65% of fluoxetine patients were much or very much improved. Fluoxetine was associated more frequently with nausea (p less than .05), while nortriptyline was associated more frequently with dry mouth (p less than .05). These results are discussed in the context of selecting between nortriptyline and fluoxetine for a particular depressed patient.

  9. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism.

    PubMed

    Tyler, Christina R; Solomon, Benjamin R; Ulibarri, Adam L; Allan, Andrea M

    2014-09-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.

  10. Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

    ERIC Educational Resources Information Center

    Tao, Rongrong; Emslie, Graham; Mayes, Taryn; Nakonezny, Paul; Kennard, Betsy; Hughes, Carroll

    2009-01-01

    The rate of symptom improvement during the early weeks of acute fluoxetine treatment is a good indicator of remission. This finding was made after evaluating the outcome of the fluoxetine treatment on 168 children and adults with depression.

  11. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    PubMed

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment.

  12. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.

    PubMed

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-07-28

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals.

  13. Treatment of depression in older adults beyond fluoxetine

    PubMed Central

    Wagner, Gabriela Arantes

    2015-01-01

    This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet. PMID:25830872

  14. Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.

    PubMed

    Bagdy, G; Graf, M; Anheuer, Z E; Modos, E A; Kantor, S

    2001-12-01

    The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0.2 mg/kg, i.p. In contrast, the selective 5-HT1A receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants. Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.

  15. Diagnosis and Fluoxetine Treatment of Compulsive Behavior Disorder of Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Bodfish, James W.; Madison, James T.

    1993-01-01

    Ten adults with compulsive behavior disorder and six comparison subjects, all with mental retardation, were treated using the medication fluoxetine. Seven of the 10 experimental subjects responded favorably to fluoxetine treatment; none of the comparison subjects responded favorably to the medication. There appeared to be a relation between…

  16. Fluoxetine treatment of acral lick dermatitis in dogs: a placebo-controlled randomized double blind trial.

    PubMed

    Wynchank, D; Berk, M

    1998-01-01

    The aim of the study was to assess the efficacy and tolerability of fluoxetine treatment of acral lick dermatitis (ALD) in dogs and to investigate ALD as an animal model of obsessive-compulsive disorder (OCD). Sixty-three dogs with ALD were treated with fluoxetine 20 mg daily, or placebo, for 6 weeks. In the fluoxetine group, owners rated both appearance of the lesion (t = 10.2, df = 29, P < 0.0001) and licking behavior (t = 10.2, df = 29, P < 0.0001) as significantly improved by the end of the trial. Veterinarian-rated pre- and post-treatment photographs showed statistically significant improvement in the fluoxetine group (mean = 2.55). There were no significant changes in the placebo group as rated by owners and veterinarians. These results demonstrate the efficacy of fluoxetine in the treatment of ALD and lend further support to ALD as an animal model of OCD.

  17. Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.

    PubMed

    Stanford, John A; Currier, Theresa D; Gerhardt, Greg A

    2002-01-01

    Spontaneous locomotor activity was measured in young (6-8 months) and aged (24-26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of fluoxetine, sertraline, or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine diminished all three behavioral measures in the young rats, while in the old rats, fluoxetine's effects were limited to a robust attenuation of vertical activity. Sertraline decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike fluoxetine, sertraline produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.

  18. The effects of chronic fluoxetine treatment following injury of medial frontal cortex in mice.

    PubMed

    McAllister, Brendan B; Spanswick, Simon C; Patel, Payal P; Barneto, Alison A; Dyck, Richard H

    2015-09-01

    Injury of the brain is a leading cause of long-term disability. Recent evidence indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be beneficial when administered following brain injury. However, its potential to promote recovery and the mechanisms by which it might do so require further characterization. In the present experiment, fluoxetine was administered to mice for 4 weeks following injury of medial frontal cortex (MFC). MFC injury altered behavior, reducing locomotion, decreasing swim speed in the Morris water task, and decreasing anxiety-like behavior in the elevated plus maze. Fluoxetine treatment did not affect these behavioral alterations, but it did increase the social dominance of the injured mice, as assessed by the tube test. Fluoxetine treatment also hastened learning of a T-maze position discrimination task, independently of lesion condition. Anatomically, fluoxetine failed to decrease lesion size, increase the survival of cells born 1-week post injury in the hippocampal dentate gyrus, or reverse the reduction in spine density in layer II/III pyramidal neurons in cingulate cortex caused by the lesions. Fluoxetine did, however, increase the dendritic arborization of these cells, which was reduced in the mice with lesions. Thus, while not all the effects of MFC injury were ameliorated, the behavioral outcome of mice with MFC injuries was improved, and one of the neuroanatomical sequelae of the lesions counteracted, by chronic fluoxetine, further contributing to the evidence that fluoxetine could be a useful treatment following brain injury.

  19. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia.

    PubMed

    Fava, Maurizio; Hoog, Sharon L; Judge, Rajinder A; Kopp, Joan B; Nilsson, Mary E; Gonzales, Jill S

    2002-04-01

    This study assessed whether fluoxetine, sertraline, and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes. Patients (N = 284) with DSM-IV major depressive disorder were randomly assigned in a double-blind fashion to fluoxetine, paroxetine, or sertraline for 10 to 16 weeks of treatment. Using the Hamilton Rating Scale for Depression (HAM-D) sleep disturbance factor score, patients were categorized into low (<4) or high (>or=4) baseline insomnia subgroups. Changes in depression and insomnia were assessed. Safety assessments included treatment-emergent adverse events (AEs), reasons for discontinuation, and AEs leading to discontinuation. In addition, AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation. Depression improvement, assessed with the HAM-D-17 total score, was similar among treatments in all patients (p = 0.365) and the high (p = 0.853) and low insomnia (p = 0.415) subgroups. Insomnia improvement, assessed with the HAM-D sleep disturbance factor score, was similar among treatments in all patients (p = 0.868) and in the high (p = 0.852) and low insomnia (p = 0.982) subgroups. Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening, any worsening, worsening at endpoint, or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup. Treatments were well tolerated in most patients. No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups. These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine, sertraline, and paroxetine in major depressive disorder patients. Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia.

  20. Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.

    PubMed

    Faillace, M P; Zwiller, J; Bernabeu, R O

    2015-08-06

    Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy.

  1. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.

    PubMed

    Sechter, D; Troy, S; Paternetti, S; Boyer, P

    1999-03-01

    Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items

  2. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness

    PubMed Central

    Hamilton, Trevor James; Kwan, Garfield T.; Gallup, Joshua; Tresguerres, Martin

    2016-01-01

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab. PMID:26806870

  3. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness.

    PubMed

    Hamilton, Trevor James; Kwan, Garfield T; Gallup, Joshua; Tresguerres, Martin

    2016-01-25

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.

  4. Serotonin and suicidality: the impact of acute fluoxetine administration. I: Serotonin and suicide.

    PubMed

    King, R A; Segman, R H; Anderson, G M

    1994-01-01

    The general enhancement of central serotonin (5-HT) neurotransmission following long-term administration of serotonin-selective reuptake inhibitors (SSRIs) appears to play an important role in these drugs' anti-depressant efficacy. Because suicide and/or aggression appear linked to diminished levels of brain 5-HT and its metabolites, it has been suggested that SSRIs may be particularly effective in reducing suicidality. Case reports of increased or new suicidal ideation following administration of fluoxetine and other SSRIs, however, raise questions about how these potential side effects may relate to the SSRI's acute effects on 5-HT transmission. Part I of this review examines fluoxetine's effects on suicidality and related behaviors and reviews the relationship of suicidality to serotonergic dysregulation.

  5. Predictors and Moderators of Acute Outcome in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Curry, John; Rohde, Paul; Simons, Anne; Silva, Susan; Vitiello, Benedetto; Kratochvil, Christopher; Reinecke, Mark; Feeny, Norah; Wells, Karen; Pathak, Sanjeev; Weller, Elizabeth; Rosenberg, David; Kennard, Betsy; Robins, Michele; Ginsburg, Golda; March, John

    2006-01-01

    Objective: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Method: Potential baseline…

  6. Effect of long-term fluoxetine treatment on the human serotonin transporter in Caco-2 cells.

    PubMed

    Iceta, Ruth; Mesonero, José E; Alcalde, Ana I

    2007-03-27

    Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) broadly used in the treatment of human mood disorders and gastrointestinal diseases involving the serotoninergic system. The effectiveness of this therapy depends on repeated long-term treatment. Most of the long-term studies in vivo of SSRI effects on serotoninergic activity have focused on their effects on autoreceptors or postsynaptic receptors. The chronic effect of SSRIs on the activity of the serotonin transporter (SERT) has been less studied and the results have been contradictory. The aim of this study was to determine the specific effect of long-term fluoxetine treatment on human serotonin transporter (hSERT) in vitro, by using the human enterocyte-like cell line Caco-2. Results show that fluoxetine diminished the 5-HT uptake in a concentration-dependent way and that this effect was reversible. Fluoxetine affected mainly the hSERT transport rate by reducing the availability of the transporter in the membrane with no significant alteration of either the total hSERT protein content or the hSERT mRNA level. These results suggest that the effect of fluoxetine on the expression of hSERT is post-translational and has shown itself to be independent of PKC and PKA activity. This study may be useful to clarify the effect of the long-term fluoxetine therapy in both gastrointestinal and central nervous system disorders.

  7. Fluoxetine treatment reverses the intergenerational impact of maternal separation on fear and anxiety behaviors.

    PubMed

    Xiong, Gui-Jing; Yang, Yuan; Cao, Jun; Mao, Rong-Rong; Xu, Lin

    2015-05-01

    Early life stress increases risks of fear and anxiety related disorders in adulthood, which may be alleviated by fluoxetine treatment. However, the intergenerational impacts of maternal separation (MS) on fear and anxiety behaviors from father to their offspring are little known. And the potential effects of fluoxetine treatment on the intergenerational transmission have not been well tested. Here, we investigated whether fluoxetine can reverse the intergenerational effects of MS on fear and anxiety behaviors. The first generation (F1) male rats were exposed to MS 3 h daily from postnatal day 2-14 and then treated with fluoxetine for four weeks during adulthood before fear conditioning. We found that maternal separation significantly impaired contextual fear extinction in F1 adult male rats but not in their second generation (F2). Although no obvious effects of MS on anxiety were observed in F1 male rats, the F2 offspring displayed a phenotype of low anxiety-like behaviors despite they were reared in normal condition. Fluoxetine treatment in F1 males not only reversed the impairment of fear extinction in F1 males but also the low anxiety-like behaviors in their F2 offspring. These findings highlight the intergenerational impacts of early life stress on fear and anxiety behaviors, and provide a new sight of the intergenerational effect of fluoxetine therapy for early life stress related mental problems.

  8. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

    PubMed Central

    Beasley, C M; Dornseif, B E; Bosomworth, J C; Sayler, M E; Rampey, A H; Heiligenstein, J H; Thompson, V L; Murphy, D J; Masica, D N

    1991-01-01

    OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES--Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS--Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17

  9. Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure

    DTIC Science & Technology

    2010-07-01

    1-0283 TITLE: Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure...SUBTITLE Predictors of Treatment Response to 5a. CONTRACT NUMBER W81XWH-07-1-0283 Fluoxetine in PTSD Following a Recent History of...controlled trial of fluoxetine as an early intervention for recently redeployed soldiers, as well as to develop methodologies for understanding the

  10. Treatment of Transvestic Fetishism With Fluoxetine: A Case Report

    PubMed Central

    Usmani, Mohammad Amir; K Gaur, Rakesh; Ahmad Azmi, Suhail; Gangwar, Sheshank

    2012-01-01

    Transvestic fetishism is having a sexual or erotic interest in cross-dressing. This case report describes a 17-year-old male with transvestic fetishism who suffered from obsessive thoughts and subsequent masturbation as compulsion. He was managed successfully with fluoxetine. PMID:24644490

  11. Ecchymoses as an adverse effect of fluoxetine treatment.

    PubMed

    Fountoulakis, Konstantinos N; Samolis, Stavros; Iacovides, Apostolos; St Kaprinis, George

    2007-07-30

    We report a case of a 28-year-old major depressive female patient who manifested ecchymoses following fluoxetine use. After substitution of sertraline, her depression resolved after 4 weeks and ecchymoses 1.5 months latter. This is an unexplored side-effect with unknown long-term consequences that warrants further study.

  12. Chronic fluoxetine treatment alters the structure, connectivity and plasticity of cortical interneurons.

    PubMed

    Guirado, Ramon; Perez-Rando, Marta; Sanchez-Matarredona, David; Castrén, Eero; Nacher, Juan

    2014-10-01

    Novel hypotheses suggest that antidepressants, such as the selective serotonin reuptake inhibitor fluoxetine, induce neuronal structural plasticity, resembling that of the juvenile brain, although the underlying mechanisms of this reopening of the critical periods still remain unclear. However, recent studies suggest that inhibitory networks play an important role in this structural plasticity induced by fluoxetine. For this reason we have analysed the effects of a chronic fluoxetine treatment in the hippocampus and medial prefrontal cortex (mPFC) of transgenic mice displaying eGFP labelled interneurons. We have found an increase in the expression of molecules related to critical period plasticity, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), GAD67/65 and synaptophysin, as well as a reduction in the number of parvalbumin expressing interneurons surrounded by perineuronal nets. We have also described a trend towards decrease in the perisomatic inhibitory puncta on pyramidal neurons in the mPFC and an increase in the density of inhibitory puncta on eGFP interneurons. Finally, we have found that chronic fluoxetine treatment affects the structure of interneurons in the mPFC, increasing their dendritic spine density. The present study provides evidence indicating that fluoxetine promotes structural changes in the inhibitory neurons of the adult cerebral cortex, probably through alterations in plasticity-related molecules of neurons or the extracellular matrix surrounding them, which are present in interneurons and are known to be crucial for the development of the critical periods of plasticity in the juvenile brain.

  13. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.

    PubMed

    De Foubert, G; Carney, S L; Robinson, C S; Destexhe, E J; Tomlinson, R; Hicks, C A; Murray, T K; Gaillard, J P; Deville, C; Xhenseval, V; Thomas, C E; O'Neill, M J; Zetterström, T S C

    2004-01-01

    Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be implicated in the clinical action of antidepressant drugs. Repeated (2-3 weeks) administration of antidepressant drugs increases BDNF gene expression. The onset of this response as well as concomitant effects on the corresponding BDNF protein is however, unclear. The present study investigated the effects of acute and chronic administration of the selective serotonin reuptake inhibitor, fluoxetine (10mg/kg p.o.), upon regional rat brain levels of BDNF mRNA and protein expression. To improve the clinical significance of the study, fluoxetine was administered orally and mRNA and protein levels were determined ex vivo using the techniques of in situ hybridisation histochemistry and immunocytochemistry respectively. Direct measurement of BDNF protein was also carried out using enzyme-linked immunosorbent assay (ELISA). Four days of once daily oral administration of fluoxetine induced decreases in BDNF mRNA (hippocampus, medial habenular and paraventricular thalamic nuclei). Whilst 7 days of treatment showed a non-significant increase in BDNF mRNA, there were marked and region-specific increases following 14 days of treatment. BDNF protein levels remained unaltered until 21 days of fluoxetine treatment, when the numbers of BDNF immunoreactive cells were increased, reaching significance in the pyramidal cell layer of CA1 and CA3 regions of Ammon's horn (CA1 and CA3) but not in the other sub-regions of the hippocampus. Indicative of the highly regional change within the hippocampus, the ELISA method failed to demonstrate significant up-regulation at 21 days, measuring levels of BDNF protein in the whole hippocampus. In contrast to the detected time dependent and biphasic response of the BDNF gene, activity-regulated, cytoskeletal-associated protein (Arc) mRNA showed a gradual increase during the 14-day course of treatment. The results presented here show that BDNF is expressed differentially

  14. Open fluoxetine treatment of mixed anxiety disorders in children and adolescents.

    PubMed

    Fairbanks, J M; Pine, D S; Tancer, N K; Dummit, E S; Kentgen, L M; Martin, J; Asche, B K; Klein, R G

    1997-01-01

    An open-label pilot study examined fluoxetine treatment in 16 outpatients (9-18 years old) with mixed anxiety disorders. Following nonresponse to psychotherapy, fluoxetine monotherapy was started at 5 mg daily and was increased weekly by 5 or 10 mg daily for 6-9 weeks until improvement occurred or to a maximum of 40 mg (children under 12) or 80 mg (adolescents). Among patients on fluoxetine, severity of illness ratings were "much improved" (mean final Clinical Global Impression scale score 2.8 +/- 0.7). Clinical improvement occurred in 10 of 10 patients with current separation anxiety disorder, 8 of 10 with social phobia, 4 of 6 with specific phobia, 3 of 5 with panic disorder, and 1 of 7 with generalized anxiety disorder. Mean time to improvement was 5 weeks. Mean doses were 24 mg (0.7 mg/kg) for children and 40 mg (0.71 mg/kg) for adolescents. Side effects were transient and included drowsiness (31% of patients), sleep problems (19%), decreased appetite (13%), nausea (13%), abdominal pain (13%), and excitement (13%). No patient developed disinhibition, akathisia, or suicidality. These preliminary findings suggest fluoxetine effectiveness in separation anxiety disorder and social phobia. Youths with only one anxiety disorder appeared to respond to lower doses of fluoxetine than patients with multiple anxiety disorders (0.49 +/- 0.14 versus 0.80 +/- 0.28 mg/kg, p < 0.05).

  15. Fluoxetine Treatment for Prevention of Relapse of Depression in Children and Adolescents: A Double-Blind, Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Heiligenstein, John H.; Hoog, Sharon L.; Wagner, Karen Dineen; Findling, Robert L.; McCracken, James T.; Nilsson, Mary E.; Jacobson, Jennie G.

    2004-01-01

    Objective: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of [less than or equal to]28 during treatment with fluoxetine 20 to 60 mg. Method: In this 32-week relapse-prevention phase of a…

  16. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine

    PubMed Central

    Pei, Siran; Liu, Li; Zhong, Zhaomin; Wang, Han; Lin, Shuo; Shang, Jing

    2016-01-01

    Fluoxetine is widely used to treat depression, including depression in pregnant and postpartum women. Studies suggest that fluoxetine may have adverse effects on offspring, presumably through its action on various serotonin receptors (HTRs). However, definitive evidence and the underlying mechanisms are largely unavailable. As initial steps towards establishing a human cellular and animal model, we analyzed the expression patterns of several HTRs through the differentiation of human induced pluripotent stem (hiPS) cells into neuronal cells, and analyzed expression pattern in zebrafish embryos. Treatment of zebrafish embryos with fluoxetine significantly blocked the expression of multiple HTRs. Furthermore, fluoxetine gave rise to a change in neuropsychology. Embryos treated with fluoxetine continued to exhibit abnormal behavior upto 12 days post fertilization due to changes in HTRs. These findings support a possible long-term risk of serotonin pathway alteration, possibly resulting from the “placental drug transfer”. PMID:27703173

  17. The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors

    PubMed Central

    Duncan, Marilyn J.; Hester, James M.; Hopper, Jason A.; Franklin, Kathleen M.

    2010-01-01

    Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment. PMID:20525077

  18. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.

    PubMed

    Sanmukhani, Jayesh; Anovadiya, Ashish; Tripathi, Chandrabhanu B

    2011-01-01

    Curcumin is the active ingredient of commonly used spice Curuma longa Linn. In the present study, the antidepressant like activity of curcumin and its combination with fluoxetine and imipramine was studied in acute model (three doses 24, 5 and 1 h before test) of forced swimming test (FST) in glass jar and tail suspension test (TST) in mice and in chronic model (14 day study) of FST with water wheel in rats. All the tests were carried out in the following seven groups (n = 6 in each group), drugs being given orally (doses for mice): Group 1 (vehicle), group 2 (curcumin 50 mg/kg), group 3 (curcumin 100 mg/kg), group 4 (fluoxetine 20 mg/kg), group 5 (imipramine 15 mg/kg), group 6 (curcumin 100 mg/kg plus fluoxetine 20 mg/kg) and group 7 (curcumin 100 mg/kg plus imipramine 15 mg/kg). Equivalent doses for rats were used. Both the acute model of FST and TST, and the chronic model of FST with water wheel showed significant antidepressant like activity of curcumin in 100 mg/kg dose as compared to vehicle control (p < 0.05). The effect of curcumin (100 mg/kg) was similar to that of fluoxetine and imipramine (p > 0.05) but its addition to fluoxetine and imipramine did not improve their antidepressant activity (p > 0.05). Curcumin increased both the swimming and climbing behavior in FST, thus its antidepressant like activity could be due to an increase in serotonin, norepinephrine and dopamine levels in the brain. Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain.

  19. Comparative evaluation between hypericin (hypiran) and fluoxetine in treatment of companion dogs with tail chasing

    PubMed Central

    Mosallanejad, Bahman; Najafzadeh Varzi, Hossein; Avizeh, Reza; Pourmahdi, Mahdi; Khalili, Fatemeh

    2015-01-01

    The aim of the present study was to compare the effects of hypericin and fluoxetine in the treatment of companion dogs with tail chasing in Ahvaz district. In the present survey, eighteen dogs with tail chasing were assigned into three equal groups for a three-year period. The dogs were randomly classified based on different treatment groups. During 15 weeks, dogs of group A were given 0.05 mg kg-1 hypericin orally and dogs of group B received 1 mg kg-1 fluoxetine, orally. The group C was the control group. Changes in signs of tail chasing were weekly reported by the owners or a veterinarian. Treatment periods were assessed in five intervals: weeks 1-3, 4-6, 7-9, 10-12 and weeks 13-15, respectively. Hypericin (group A) was significantly more effective in the treatment of tail chasing compared with fluoxetine (group B), (p = 0.043). Statistical analysis revealed a significant difference in each group between weeks 1-3 (X2 = 8.8, p = 0.01), 4-6 (X2 = 9.1, p = 0.01), 7-9 (X2 = 7.4, p = 0.03), 10-12 (X2 = 10.4, p = 0.005) and 13-15 (X2 = 12.5, p = 0.002). Improvement of behavior in the dogs of group A was significant compared with group B, between weeks 10-12 (X2 = 5.4, p = 0.02) and 13-15 (X2 = 7.2, p = 0.007). In conclusion, our survey showed that hypericin was more effective than fluoxetine in controlling signs of tail chasing. PMID:26261714

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

    PubMed

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

    2014-01-01

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

  1. Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues.

    PubMed

    da Silva, Aline Isabel; Braz, Glauber Ruda Feitoza; Silva-Filho, Reginaldo; Pedroza, Anderson Apolonio; Ferreira, Diorginis Soares; Manhães de Castro, Raul; Lagranha, Claudia

    2015-06-01

    Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

  2. Sertraline and fluoxetine treatment of obsessive-compulsive disorder: results of a double-blind, 6-month treatment study.

    PubMed

    Bergeron, Richard; Ravindran, Arun V; Chaput, Yves; Goldner, Elliot; Swinson, Richard; van Ameringen, Michael A; Austin, Carol; Hadrava, Vratislav

    2002-04-01

    The purpose of this study was to evaluate the comparative efficacy and tolerability of sertraline and fluoxetine in the treatment of obsessive-compulsive disorder (OCD). Outpatients meeting DSM-IV criteria for OCD, with a Yale-Brown Obsessive-Compulsive (Y-BOCS) total score >or= 17, an NIMH Global Obsessive-Compulsive (NIMH-OC) scale score >or= 7, and a CGI-Severity score >or= 4 were randomized to 24 weeks of double-blind treatment with sertraline (N = 77) or fluoxetine (N = 73). Primary efficacy measures consisted of the Y-BOCS, the NIMH-OC scale, and the CGI-Severity (CGI-S) and Improvement (CGI-I) scales. Equivalent and significant (p < 0.001) improvement was found at week 24 in Y-BOCS and NIMH-OC scale scores for sertraline and fluoxetine. After 12 weeks, 49.2% of patients on sertraline were rated on the CGI-S scale as being mildly ill or not ill compared to 24.6% on fluoxetine (p < 0.01). A Cox analysis found patients on sertraline to have a statistically nonsignificant 42% greater likelihood of achieving a response by week 12 (CGI-I, much or very much improved; 95% CI, 0.85, 2.38; p = 0.18). Sertraline treatment also resulted in a higher proportion of remissions than fluoxetine (defined as a CGI-I treatment of outpatients with moderate to severe OCD with the subjects treated with sertraline showing a greater likelihood of remission as well as an earlier improvement on some but not all efficacy measures

  3. Sertraline versus fluoxetine in the treatment of major depression: a combined analysis of five double-blind comparator studies.

    PubMed

    Feiger, Alan D; Flament, Martine F; Boyer, Patrice; Gillespie, John A

    2003-07-01

    The aim of this study was to examine response and remission rates in outpatients treated with sertraline or fluoxetine who were suffering from two depression subtypes: anxious-depression and severe depression. Data were pooled from five double-blind studies comparing fluoxetine versus sertraline for the treatment of DSM-III-R or IV major depression. Clinical outcome was assessed using the Hamilton Depression Rating Scale (HAM-D) and the Clinical Global Impression-Improvement scale (CGI-I). One thousand and eighty-eight patients were randomized, with 654 (60%) meeting criteria for anxious depression and 212 (19%) meeting criteria for high severity depression. For the total sample, treatment response was similar for both sertraline and fluoxetine. In the high severity subgroup, the mean (+/-SD) HAM-D score at week 12 was 8.9+/-5.7 for sertraline and 10.8+/-6.9 for fluoxetine (P=0.07), and the mean (+/-SD) CGI-I score was 1.5+/-0.7 for sertraline and 2.0+/-1.1 for fluoxetine (P=0.005). CGI-I responder rates were 88% versus 71% (P=0.03) in the high severity subgroup, and 84% versus 79% (P=0.16) in the anxious-depression subgroup. Overall, sertraline and fluoxetine showed comparable antidepressant efficacy, although sertraline may offer an advantage in those patients with severe depression.

  4. Nortriptyline versus fluoxetine in the treatment of major depressive disorder: a six-month, double-blind clinical trial

    PubMed Central

    Hashemi, SN; Shirazi, HR Ghafarian; Mohammadi, A; Zadeh-Bagheri, GH; Noorian, KH; Malekzadeh, M

    2012-01-01

    Background Depression is a common psychiatric disorder worldwide, including in Iran, and is estimated to affect 10%–15% of the population. Antidepressant drugs can have multiple side effects, so a good choice of drug is important for successful treatment. This study compared the efficacy of nortriptyline with that of fluoxetine in the treatment of patients with major depressive disorder and assessed related factors, including age, gender, and level of education. Methods The study was a double-blind, randomized clinical trial with a six-month follow-up period. Participants were 120 patients aged 15–60 years with a diagnosis of major depressive disorder based on a psychiatry interview and the Beck depression rating scale, which were performed at the beginning, middle, and end of the study. The patients were treated with nortriptyline or fluoxetine. The paired t-test, independent t-test, and the k chi-square test were used to analyze the data. Results Twenty-three patients dropped out and 97 remained in the trial. Before intervention, the mean depression score was 32.85 ± 6.23 in the nortriptyline group and 33.12 ± 6.50 in the fluoxetine group. The results of the independent t-test showed a significant difference between depression score means before and after treatment in both groups. Changes at the end of the trial compared with baseline scores were 13.4 ± 4.68 and 16.96 ± 4.96 for nortriptyline and fluoxetine, respectively. Paired t-testing showed a significant difference in the mean depression score for both the nortriptyline and fluoxetine groups. Age, gender, and level of education had no significant effects on the outcome of treatment in the two groups. Conclusion The present study suggests that both nortriptyline and fluoxetine were effective in the treatment of depression, but that fluoxetine was more effective than nortriptyline after 3 and 6 months of treatment. PMID:22359466

  5. Quetiapine add-on therapy improves the depressive behaviors and hippocampal neurogenesis in fluoxetine treatment resistant depressive rats.

    PubMed

    Wang, Ying; Chang, Ting; Chen, Yun-Chun; Zhang, Rui-Guo; Wang, Hua-Ning; Wu, Wen-Jun; Peng, Zheng-Wu; Tan, Qing-Rong

    2013-09-15

    Quetiapine, an atypical antipsychotic, may have efficacy as augmentation therapy in treatment resistant depression (TRD), but evidence is limited and the underlying mechanism remains poorly understood. Therefore, this study was aimed to investigate whether and how quetiapine can be served as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral tests and hippocampal neurogenesis. Approximately 20-30% of depressive rats respond poorly to fluoxetine treatment. In their hippocampus, a significant decrease of neurogenesis was also observed. However, quetiapine add-on therapy significantly improved the depressive behaviors and increased the number of the newborn neurons in the hippocampus of fluoxetine treatment resistant depressive rats. Thus, our results suggest that quetiapine may be used as an augmentation agent in the treatment resistant depression partly mediated by increasing the number of newborn neurons in the hippocampus.

  6. Citalopram versus fluoxetine for the treatment of patients with bulimia nervosa: a single-blind randomized controlled trial.

    PubMed

    Leombruni, Paolo; Amianto, Federico; Delsedime, Nadia; Gramaglia, Carla; Abbate-Daga, Giovanni; Fassino, Secondo

    2006-01-01

    The most studied and most frequently used pharmacologic treatments in bulimia nervosa are the selective serotonin reuptake inhibitors (SSRIs), in particular, fluoxetine. Less is known about the efficacy of the other SSRIs. To compare fluoxetine with citalopram in the treatment of bulimic patients, 37 bulimic patients were randomized to receive fluoxetine (n=18) or citalopram (n=19); these patients were assessed with regard to clinical (ie, body mass index, pathologic behaviors), psychopathologic (Eating Disorder Inventory-2, Body Shape Questionnaire, Binge-Eating Scale, Beck Depression Inventory), personality (Temperament and Character Inventory), and clinical global impression measures. These measures were compared between the 2 treatment groups at baseline and at the end of treatment. Dropout rates were similar in the 2 groups. Both groups showed significant improvement in eating psychopathology, angry feelings, and clinical global impression. Patients in the fluoxetine group displayed a greater reduction in introjected anger, whereas those in the citalopram group displayed a greater reduction in depressive feelings. Both treatments showed some effect on outcome measures, but efficacy profiles did not overlap. Citalopram may be useful in depressed patients with bulimia, whereas fluoxetine is more specific for those with introjected anger and bulimia.

  7. Fluoxetine for the Treatment of Childhood Anxiety Disorders: Open-Label, Long-Term Extension to a Controlled Trial

    ERIC Educational Resources Information Center

    Clark, Duncan B.; Birmaher, Boris; Axelson, David; Monk, Kelly; Kalas, Catherine; Ehmann, Mary; Bridge, Jeffrey; Wood, D. Scott; Muthen, Bengt; Brent, David

    2005-01-01

    Objective: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. Method: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they…

  8. Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

    PubMed

    Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

    2008-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

  9. Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study.

    PubMed

    Pardini, Matteo; Guida, Silvia; Primavera, Alberto; Krueger, Frank; Cocito, Leonardo; Gialloreti, Leonardo Emberti

    2011-03-01

    Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

  10. The effects of sertraline and fluoxetine on anxiety in the elevated plus-maze test in mice.

    PubMed

    Kurt, M; Arik, A C; Celik, S

    2000-01-01

    The aim of this study was to evaluate the acute and chronic effects of two SSRIs (sertraline and fluoxetine) on anxiety by the elevated plus-maze test. Diazepam increased the time spent in open arms significantly whereas the anxiogenic m-chlorophenylpiperazine (m-CPP) decreased the time significantly. Acute sertraline (10 mg x kg(-1)) and fluoxetine (20 mg x kg(-1)) treatment significantly decreased the time spent in open arms. Acute fluoxetine (20 mg x kg(-1)) treatment also decreased the total number of enclosed arm entries. Seven days sertraline treatment decreased the time spent in open arms, whereas 14 days fluoxetine treatment increased the time spent in open arms. These results show that acute administration of SSRIs may produce anxiogenic effects in the elevated plus-maze test.

  11. SET-C versus Fluoxetine in the Treatment of Childhood Social Phobia

    ERIC Educational Resources Information Center

    Beidel, Deborah C.; Turner, Samuel M.; Ammerman, Robert T.; Sallee, Floyd R.; Crosby, Lori A.; Pathak, Sanjeev

    2007-01-01

    A study examines the effectiveness of fluoxetine, pill placebo and Social Effectiveness Therapy for Children (SET-C) for children and adolescents with social phobia. The results conclude that both fluoxetine and SET-C are effective for social phobia but SET-C is better for enhancing social skills.

  12. Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial

    PubMed Central

    2013-01-01

    Background Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is a subtype of stroke that causes a great amount of disability and economic and social burden. This is particularly true in developing countries where it accounts for between 20% and 50% of all strokes. Pharmacological and surgical interventions have been attempted to reduce the mortality and disability caused by ICH, with unsuccessful results. Recently, the use of fluoxetine in addition to physical rehabilitation has been proven useful to improve motor recovery following cerebral infarct. The purpose of this study is to test whether a 3-month treatment with fluoxetine enhances motor recovery in nondepressed patients with acute intracerebral hemorrhage. Methods/design Our study is a randomized, double-blind, placebo-controlled, multicenter clinical trial. We will recruit 86 patients with intracerebral hemorrhage of both sexes, aged >18 years, from four Mexican hospitals. The patients will receive either 20 mg of fluoxetine or a placebo once daily for 90 days. The primary outcome is the mean change in the Fugl-Meyer Motor Scale score between inclusion (day 0) and day 90. The secondary outcomes will be changes in the Barthel Index, the Modified Rankin scale and the National Institutes of Health stroke scale. The outcomes will be measured at day 42 ± 7days and at day 90, for a total of four visits with each subject (at screening and at 0, 42 and 90 days). Discussion Current guidelines recommend early supported hospital discharge and home-based rehabilitation programs as the only cost-effective intervention to aid the recovery of patients with intracerebral hemorrhage. Nevertheless, such interventions are dependent on available resources and funding, which make them very difficult to implement in developing countries. We believe that the identification of a helpful pharmacological intervention to aid the motor recovery of these patients will constitute a breakthrough that will have a major impact in

  13. Effect of repeated co-treatment with fluoxetine and amantadine on the behavioral reactivity of the central dopamine and serotonin system in rats.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna

    2009-01-01

    In the present study we found that repeated co-treatment with fluoxetine and amantadine for 14 days (but not for 7 days) enhanced the hyperactivity induced by amphetamine or quinpirole (a dopamine D(2/3) agonist), compared to treatment with either drug alone. Whereas repeated co-treatment with fluoxetine and amantadine for 7 days more potently inhibited the behavioral syndrome evoked by the 5-hydroxytryptamine (5-HT)(1A) receptor agonist (+/-)-8-hydroxy-2(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT), it did not change the action of the 5-HT(2) receptor agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (/+/-/-DOI). The obtained results support the hypothesis that repeated co-treatment with fluoxetine and amantadine may evoke more effective antidepressant activity than treatment with fluoxetine alone. Moreover, our results suggest that 5-HT(1A) receptors are useful targets for the development of more rapidly acting and more effective medication.

  14. Persistent infection of human pancreatic cells with Coxsackievirus B4 is cured by fluoxetine.

    PubMed

    Alidjinou, Enagnon Kazali; Sané, Famara; Bertin, Antoine; Caloone, Delphine; Hober, Didier

    2015-04-01

    Group B Coxsackieviruses (CVB) are involved in various acute clinical features and they can play a role in the development of chronic diseases like type 1 diabetes. The persistence of CVB has been described in vitro and in vivo in various models. Fluoxetine was reported to inhibit the replication of CVB1-3, which prompted us to study the in vitro antiviral activity of fluoxetine against CVB4 in models of acute infection. In addition we took advantage of a chronically CVB4-infected Panc-1 cell line to evaluate the antiviral effect of fluoxetine in a model of persistent CVB4 infection. An inhibition of the CVB4 replication was obtained when fluoxetine was added at 5.48μM to Hep-2 cell cultures. No inhibitory effect was observed when CVB4 was mixed with fluoxetine for 2h and filtered to eliminate fluoxetine before inoculation to cells, or when cells were treated up to 96h and washed before viral inoculation. Fluoxetine (5.48μM) reduced viral replication by more than 50% in acutely infected Panc-1 cell cultures. A dramatic decrease of infectious particles levels in supernatants of Panc-1 cells chronically infected with CVB4 was obtained a few days after treatment with fluoxetine and no infectious viral particle was found as soon as day 21 of treatment, and intracellular enteroviral RNA was undetectable by RT-PCR after three weeks of treatment. These data display that fluoxetine can inhibit the replication of CVB4 and can cure Panc-1 cells chronically infected with CVB4.

  15. Aquatic toxicology of fluoxetine: understanding the knowns and the unknowns.

    PubMed

    Stewart, Adam Michael; Grossman, Leah; Nguyen, Michael; Maximino, Caio; Rosemberg, Denis Broock; Echevarria, David J; Kalueff, Allan V

    2014-11-01

    Fluoxetine is one of the most prescribed psychotropic medications, and is an agent of increasing interest for environmental toxicology. Fish and other aquatic organisms are excellent models to study neuroactive small molecules like fluoxetine. However, prone to variance due to experimental factors, data obtained in these models need to be interpreted with caution, using proper experimental protocols, study designs, validated endpoints as well as well-established models and tests. Choosing the treatment protocol and dose range for fluoxetine and other serotonergic drugs is critical for obtaining valid test results and correct data interpretation. Here we discuss the value of aquatic models to study fluoxetine effects, based on prior high-quality research, and outline the directions of future translational studies in the field. We review fluoxetine-evoked phenotypes in acute vs. chronic protocols, discussing them in the contact of complex role of serotonin in behavioral regulation. We conclude that zebrafish and other aquatic models represent a useful in-vivo tool for fluoxetine pharmacology and (eco)toxicology research.

  16. Potentiated gene regulation by methylphenidate plus fluoxetine treatment: Long-term gene blunting (Zif268, Homer1a) and behavioral correlates.

    PubMed

    Beverley, Joel A; Piekarski, Cassandra; Van Waes, Vincent; Steiner, Heinz

    2014-12-01

    Use of psychostimulants such as methylphenidate (Ritalin) in medical treatments and as cognitive enhancers in the healthy is increasing. Methylphenidate produces some addiction-related gene regulation in animal models. Recent findings show that combining selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine with methylphenidate potentiates methylphenidate-induced gene regulation. We investigated the endurance of such abnormal gene regulation by assessing an established marker for altered gene regulation after drug treatments - blunting (repression) of immediate-early gene (IEG) inducibility - 14 days after repeated methylphenidate+fluoxetine treatment in adolescent rats. Thus, we measured the effects of a 6-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or their combination on the inducibility (by cocaine) of neuroplasticity-related IEGs (Zif268, Homer1a) in the striatum, by in situ hybridization histochemistry. Repeated methylphenidate treatment alone produced modest gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine given in conjunction with methylphenidate produced pronounced potentiation of methylphenidate-induced blunting for both genes. This potentiation was seen in many functional domains of the striatum, but was most robust in the lateral, sensorimotor striatum. These enduring molecular changes were associated with potentiated induction of behavioral stereotypies in an open-field test. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs such as fluoxetine may increase the addiction liability of methylphenidate. Key words: cognitive enhancer, dopamine, serotonin, gene expression, psychostimulant, SSRI antidepressant, striatum.

  17. Comparison of Saffron versus Fluoxetine in Treatment of Mild to Moderate Postpartum Depression: A Double-Blind, Randomized Clinical Trial.

    PubMed

    Kashani, L; Eslatmanesh, S; Saedi, N; Niroomand, N; Ebrahimi, M; Hosseinian, M; Foroughifar, T; Salimi, S; Akhondzadeh, S

    2017-03-01

    Introduction: Postpartum depression is a common mental health problem that is associated with maternal suffering. The aim of this double-blind clinical trial was to compare safety and efficacy of saffron and fluoxetine in treatment of mild to moderate postpartum depression. Methods: This was a 6-week, double-blind, randomized clinical trial. Subjects were women aged 18-45 years with mild to moderate postpartum depression who had Hamilton Depression Rating Scale (HDRS 17-item) score≤18. Eligible participants were randomized to receive either a capsule of saffron (15 mg capsule) or fluoxetine (20 mg capsule) twice daily for 6 weeks. The primary outcome measure was to evaluate efficacy of saffron compared to fluoxetine in improving depressive symptoms (HDRS score). Results: There was no significant effect for time×treatment interaction on HDRS score [F (4.90, 292.50)=1.04, p=0.37] between the 2 groups. 13 (40.60%) patients in the saffron group experienced complete response (≥50% reduction in HDRS score) compared with 16 (50%) in the fluoxetine group and the difference between the 2 groups was not significant in this regard (p=0.61). Frequency of adverse events was not significantly different between the treatment groups. Discussion: The results of this study may suggest that saffron is a safe alternative medication for improving depressive symptoms of postpartum depression. Nevertheless, it should be mentioned that the trial is not well powered and should be considered a preliminary study. Therefore, large clinical trials with longer treatment periods and comparison with placebo group would be appropriate for future studies.

  18. Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes.

    PubMed

    Ansai, Satoshi; Hosokawa, Hiroshi; Maegawa, Shingo; Kinoshita, Masato

    2016-04-15

    Medaka (Oryzias latipes) is a small freshwater teleost that is an emerging model system for neurobehavioral research and toxicological testing. The selective serotonin reuptake inhibitor class of antidepressants such as fluoxetine is one of the widely prescribed drugs, but little is known about the effects of these drugs on medaka behaviors. To assess the behavioral effects of fluoxetine, we chronically administrated fluoxetine to medaka adult fish and analyzed the anxiety-related and social behaviors using five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and social interaction) with an automated behavioral testing system. Fish chronically treated with fluoxetine exhibited anxiolytic responses such as an overall increased time spent in the top area in the diving test and an increased time spent in center area in the open-field test. Analysis of socially evoked behavior showed that chronic fluoxetine administration decreased the number of mirror biting times in the mirror-biting test and increased latency to first contact in the social interaction test. Additionally, chronic fluoxetine administration reduced the horizontal locomotor activity in the open-field test but not the vertical activity in the diving test. These investigations are mostly consistent with previous reports in the other teleost species and rodent models. These results indicate that behavioral assessment in medaka adult fish will become useful for screening of effects of pharmaceutical and toxicological compounds in animal behaviors.

  19. Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

    ERIC Educational Resources Information Center

    Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

    2009-01-01

    The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures…

  20. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response.

    PubMed

    Panlilio, Jennifer M; Marin, Sara; Lobl, Marissa B; McDonald, M Danielle

    2016-08-08

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g(-1) FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g(-1) FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g(-1) FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia.

  1. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response

    PubMed Central

    Panlilio, Jennifer M.; Marin, Sara; Lobl, Marissa B.; McDonald, M. Danielle

    2016-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g−1 FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g−1 FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g−1 FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia. PMID:27499056

  2. Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the "spadin" Antidepressant.

    PubMed

    Vallée, Nicolas; Lambrechts, Kate; De Maistre, Sébastien; Royal, Perrine; Mazella, Jean; Borsotto, Marc; Heurteaux, Catherine; Abraini, Jacques; Risso, Jean-Jacques; Blatteau, Jean-Eric

    2016-01-01

    In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.

  3. Combination of fluoxetine and extinction treatments forms a unique synaptic protein profile that correlates with long-term fear reduction in adult mice.

    PubMed

    Popova, Dina; Ágústsdóttir, Arna; Lindholm, Jesse; Mazulis, Ulams; Akamine, Yumiko; Castrén, Eero; Karpova, Nina N

    2014-07-01

    The antidepressant fluoxetine induces synaptic plasticity in the visual and fear networks and promotes the structural remodeling of neuronal circuits, which is critical for experience-dependent plasticity in response to an environmental stimulus. We recently demonstrated that chronic fluoxetine administration together with extinction training in adult mice reduced fear in a context-independent manner. Fear conditioning and extinction alter excitatory and inhibitory transmissions within the fear circuitry. In this study, we investigated whether fluoxetine, extinction or their combination produced distinct long-lasting changes in the synaptic protein profile in the amygdala, hippocampus and prefrontal cortex of conditioned mice. We determined that extinction induced synaptophysin expression and down-regulated the GluA1:GluA2 ratio throughout the fear network in water- and fluoxetine-treated mice, suggesting a common fluoxetine-independent mechanism for increased synaptic transmission and re-arrangement of AMPA-receptors by extinction training. In contrast to common changes, the presynaptic vesicular neurotransmitter transporters VGAT and Vglut1 were upregulated after extinction in water- and fluoxetine-treated mice, respectively. The cortical levels of the GABA transporter Gat1 were reduced in high-freezing water-drinking mice, suggesting a maladaptive increase of GABA spillover at cortical inhibitory synapses. Fear conditioning decreased, and extinction induced the expression of GABA-receptor alpha1 and alpha2 subunits in water- and fluoxetine-treated mice, respectively. Only a combination of fluoxetine with extinction enhanced GluN2A expression in the amygdala and hippocampus, emphasizing the role of this NMDA-receptor subunit in the successful erasure of fear memories. Our finding provides novel data that may become helpful in developing beneficial pharmacological fear-reducing treatment strategies.

  4. Acute Treatment of Migraine

    PubMed Central

    ÖZTÜRK, Vesile

    2013-01-01

    Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse.

  5. Fluoxetine in Treatment of Adolescent Patients with Autism: A Longitudinal Open Trial.

    ERIC Educational Resources Information Center

    Fatemi, S. Hossein; Realmuto, George M.; Khan, Lubna; Thuras, Paul

    1998-01-01

    Retrospective chart reviews of seven adolescents and young adults (ages 9-20) with autistic disorder treated with fluoxetine alone or in combination with other medications were performed. Side effects included initial appetite suppression, vivid dreams, and hyperactivity. Improvement was seen in irritability, lethargy, sterotypy, and inappropriate…

  6. A randomized, double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with Binge Eating Disorder.

    PubMed

    Leombruni, Paolo; Pierò, Andrea; Lavagnino, Luca; Brustolin, Annalisa; Campisi, Stefania; Fassino, Secondo

    2008-08-01

    Previous studies support the use of selective serotonin reuptake inhibitors (SSRIs), in overweight patients with Binge Eating Disorder (BED), but results are far from conclusive. Sertraline has been studied less extensively, and there have been a few studies concerning SSRIs that report follow-up data at more than 12 weeks of follow-up. The present study assesses the effectiveness of sertraline and fluoxetine over a period of 24 weeks in obese patients with BED (DSM-IV-TR). Forty-two obese outpatients were randomized and assigned to one of two different drug treatments: 22 were treated with sertraline (dose range: 100-200 mg/day) and 20 with fluoxetine (dose range: 40-80 mg/day). Subjects were assessed at baseline and at 8, 12, and 24 weeks of treatment for binge frequency, weight loss, and severity of psychopathology. No significant differences were found between the two treatments. After 8 weeks of treatment a significant improvement in the Binge Eating Scale score and a significant weight loss emerged. These results were maintained by responders (weigh loss of at least 5% of baseline weight) over 24 weeks. The results suggest that a 6-month treatment with SSRI may be an effective option to treat patients with BED.

  7. Fluoxetine (Prozac) and Pregnancy

    MedlinePlus

    ... belongs to the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). I am taking fluoxetine, but I would ... Studies have begun to look at the possible long-term effects on infants exposed to fluoxetine during pregnancy. Fluoxetine ...

  8. Treatment of Acute Promyelocytic (M3) Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment of Acute Promyelocytic (M3) Leukemia Early diagnosis and treatment of acute promyelocytic leukemia ( ... Comes Back After Treatment? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...

  9. Fluoxetine combined with clorazepate dipotassium and behaviour modification for treatment of anxiety-related disorders in dogs.

    PubMed

    Pineda, S; Anzola, B; Olivares, A; Ibáñez, M

    2014-03-01

    The effectiveness of clorazepate dipotassium combined with fluoxetine and a behaviour modification programme for the treatment of anxiety disorders in dogs was investigated. Forty dogs with anxiety disorders were initially enrolled and 36 dogs completed the trial. Dogs were classified into two behavioural categories (anxious dogs with aggression and anxious dogs without aggression) according to their presenting complaints, and were also subdivided into males, females, juveniles and adults. The dog owners were provided with a behaviour modification plan for their dogs to be commenced in the first week of therapy. Clorazepate dipotassium was administered PO at 1.0 mg/kg every 24 h for 4 weeks, and fluoxetine was administered PO at 1.0 mg/kg every 24 h for 10 weeks. Therapy with both drugs was initiated simultaneously. Improvement was reported in 25/36 dogs. Significant differences in treatment effects were observed between anxious dogs with aggression and anxious dogs without aggression (P<0.05). Positive correlations between owner compliance with the treatment plan and reported improvement achieved during three periods of study were also noted.

  10. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study

    PubMed Central

    Roskell, Neil; Tennis, Pat; Mines, Daniel; Weich, Scott; Andrews, Elizabeth

    2007-01-01

    Objective To compare the risk of suicide in adults using the antidepressant venlafaxine compared with citalopram, fluoxetine, and dothiepin. Design Retrospective cohort study. Setting UK General Practice Research Database. Participants 219 088 patients, aged 18-89 years, who were prescribed venlafaxine, citalopram, fluoxetine, or dothiepin from 1995 to 2005. Main outcome measures Completed suicide and attempted suicide. Results Venlafaxine users had a higher burden of risk factors for suicide, including previous suicide attempts and proxies for severe depression or depression that was difficult to treat. In the analysis for completed suicides, unadjusted and adjusted hazard ratios for venlafaxine compared with citalopram were 2.44 (95% confidence interval 1.12 to 5.31) and 1.70 (0.76 to 3.80), for venlafaxine compared with fluoxetine were 2.85 (1.37 to 5.94) and 1.63 (0.74 to 3.59), and for venlafaxine compared with dothiepin were 2.54 (1.07 to 6.02) and 1.31 (0.53 to 3.25). Compared with other study drugs, venlafaxine was also associated with an increased risk of attempted suicide, but adjustment for measured confounders substantially reduced the hazard ratios. Conclusions Venlafaxine use was consistently associated with higher risk of suicide compared with citalopram, fluoxetine, and dothiepin. Venlafaxine users had a higher burden of suicide risk factors, however, and adjustment for measured confounders substantially reduced the excess risks. Since the secondary data used in this analysis allowed only indirect and partial measurements of potential confounders, it is possible that residual confounding explains much, if not all, of the observed excess risk. PMID:17164297

  11. Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.

    PubMed

    Vicente, Maria Adrielle; Zangrossi, Helio

    2012-04-01

    A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.

  12. Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice.

    PubMed

    Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-11-02

    Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus.

  13. Depression-like behaviors in tree shrews and comparison of the effects of treatment with fluoxetine and carbetocin.

    PubMed

    Meng, Xiaolu; Shen, Fang; Li, Chunlu; Li, Yonghui; Wang, Xuewei

    2016-06-01

    Tree shrews, a species phylogenetically close to primates, are regarded as a suitable and naturalistic animal model for depression studies. However, psychological symptoms that are essential for depression diagnosis and treatment, such as helplessness and social withdrawal, have not been studied in this model. Therefore, in this study, we first investigated learned helplessness, social interaction and sucrose preference induced by two chronic stress paradigms: uncontrollable foot shocks (1-week foot shocks) and multiple unpredictable stimuli (1-week foot shocks and 3-week unpredictable stressors) in tree shrews. Our results showed that uncontrollable foot shocks could only induce learned helplessness in animals; whereas animals treated with multiple unpredictable stimuli exhibited more depression-like behaviors including social withdrawal, anhedonia and learned helplessness. These findings suggested that multiple unpredictable stimuli could effectively induce various depression-like behaviors in tree shrews. More importantly, we compared the antidepressant effects of fluoxetine and carbetocin, a long-acting oxytocin analog, on specific depression-like behaviors. Our present data displayed that, compared with fluoxetine, carbetocin was also effective in reversing learned helplessness, elevating sucrose preference and improving social interaction behaviors in depression-like animals. Therefore, carbetocin might be a potential antidepressant with applications in humans.

  14. Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.

    PubMed

    Godavarthi, Swetha K; Sharma, Ankit; Jana, Nihar Ranjan

    2014-08-01

    Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities.

  15. Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

    PubMed Central

    Vallée, Nicolas; Lambrechts, Kate; De Maistre, Sébastien; Royal, Perrine; Mazella, Jean; Borsotto, Marc; Heurteaux, Catherine; Abraini, Jacques; Risso, Jean-Jacques; Blatteau, Jean-Eric

    2016-01-01

    In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate. PMID:26909044

  16. Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna

    2006-01-01

    The aim of the present study was to examine the effect of combined treatment of male Wistar rats with pramipexole and fluoxetine or sertraline in the forced swimming test. The obtained results showed that co-treatment with pramipexole (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive per se) exhibited antidepressant-like activity in the forced swimming test. Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A) receptor antagonist), either being ineffective in the forced swimming test, inhibited the antidepressant-like effect induced by co-administration of pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1) receptor antagonist) only partly did not alter the effect of pramipexole given jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3) receptor antagonist) only partly decreased (in a statistically insignificant manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of pramipexole and sertraline (but not pramipexole and fluoxetine). In that test, active behavior did not reflect the increases in general activity, since combined administration of pramipexole and fluoxetine or sertraline failed to enhance the locomotor activity of rats. None of the tested drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) - alone or in combination with pramipexole and fluoxetine or sertraline - changed locomotor activity. The results described in the present paper indicate that co-administration of pramipexole and fluoxetine or sertraline may induce a more pronounced antidepressive activity than does treatment with pramipexole alone, and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors may contribute to the antidepressant-like activity of pramipexole and fluoxetine or sertraline in the forced swimming test in rats

  17. [Treatment of acute leukemias].

    PubMed

    Gross, R; Gerecke, D

    1982-11-12

    The effective treatment of acute (myeloblastic and lymphoblastic) leukaemias depends on the induction of remissions as well as on the maintenance of these remissions. Whereas the use of anthracyclines and of cytosine arabinoside in different combinations notably increased the rate of induction of remissions, their maintenance was less successful until now. We present a scheme using, beside MTX and 6-MP, modified COAP regimes periodically every 3 months. The follow-up of 26 patients treated in this way is encouraging since nearly one third remained in full haematological remission after 3 years of observation.

  18. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

    PubMed

    Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

    2017-03-15

    Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory.

  19. Long-term treatment with fluoxetine induces desensitization of 5-HT4 receptor-dependent signalling and functionality in rat brain.

    PubMed

    Vidal, Rebeca; Valdizán, Elsa M; Mostany, Ricardo; Pazos, Angel; Castro, Elena

    2009-08-01

    The mode of action of antidepressant drugs may be related to mechanisms of monoamines receptor adaptation, including serotonin 5-HT(4) receptor subtypes. Here we investigated the effects of repeated treatment with the selective serotonin reuptake inhibitor fluoxetine for 21 days (5 and 10 mg/kg, p.o., once daily) on the sensitivity of 5-HT(4) receptors by using receptor autoradiography, adenylate cyclase assays and extracellular recording techniques in rat brain. Fluoxetine treatment decreased the density of 5-HT(4) receptor binding in the CA1 field of hippocampus as well as in several areas of the striatum over the doses of 5-10 mg/kg. In a similar way, we found a significant lower response to zacopride-stimulated adenylate cyclase activity in the fluoxetine 10 mg/kg/day treated group. Furthermore, post-synaptic 5-HT(4) receptor activity in hippocampus-measured as the excitatory action of zacopride in the pyramidal cells of CA1 evoked by Schaffer collateral stimulation was attenuated in rats treated with both doses of fluoxetine. Taken together, these results support the concept that a net decrease in the signalization pathway of 5-HT(4) receptors occurs after chronic selective serotonin reuptake inhibitor treatment: this effect may underlie the therapeutic efficacy of these drugs.

  20. Efficacy and safety of olanzapine/fluoxetine combination in the treatment of treatment-resistant depression: a meta-analysis of randomized controlled trials

    PubMed Central

    Luan, Shuxin; Wan, Hongquan; Wang, Shijun; Li, He; Zhang, Baogang

    2017-01-01

    Background Whether olanzapine/fluoxetine combination (OFC) is superior to olanzapine or fluoxetine monotherapy in patients with treatment-resistant depression (TRD) remains controversial. Thus, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of OFC with olanzapine or fluoxetine monotherapy for patients with TRD. Materials and methods RCTs published in PubMed, Embase, Web of Science, and the ClinicalTrials.gov registry were systematically reviewed to assess the efficacy and safety of OFC. Outcomes included mean changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Hamilton Rating Scale for Anxiety (HAM-A), Brief Psychiatric Rating Scale (BPRS) scores, response rate, remission rate, and adverse events. Results were expressed with weighted mean difference (WMD) with 95% confidence intervals (CIs) and risk ratio (RR) with 95% CIs. Results A total of five RCTs with 3,020 patients met the inclusion criteria and were included in this meta-analysis. Compared with olanzapine or fluoxetine monotherapy, OFC was associated with greater changes from baseline in MADRS (WMD =−3.37, 95% CI: −4.76, −1.99; P<0.001), HAM-A (WMD =−1.82, 95% CI: −2.25, −1.40; P<0.001), CGI-S (WMD =−0.37, 95% CI: −0.45, −0.28; P<0.001), and BPRS scores (WMD =−1.46, 95% CI: −2.16, −0.76; P<0.001). Moreover, OFC had significantly higher response rate (RR =1.35, 95% CI: 1.12, 1.63; P=0.001) and remission rate (RR =1.71, 95% CI: 1.31, 2.23; P<0.001). The incidence of treatment-related adverse events was similar between the OFC and monotherapy groups (RR =1.01, 95% CI: 0.94, 1.08; P=0.834). Conclusion OFC is more effective than olanzapine or fluoxetine monotherapy in the treatment of patients with TRD. Our results provided supporting evidence for the use of OFC in TRD. However, considering the limitations in this study, more large-scale, well-designed RCTs are

  1. Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.

    PubMed

    Almeida, Jeferson; Duarte, Josiane O; Oliveira, Leandro A; Crestani, Carlos C

    2015-01-01

    Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

  2. Classics in Chemical Neuroscience: Fluoxetine (Prozac)

    PubMed Central

    2013-01-01

    Fluoxetine (Prozac) was the first major breakthrough for the treatment of depression since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) nearly 30 years earlier. It was the first selective serotonin reuptake inhibitor (SSRI) approved by the United States Food and Drug Administration, offering superior efficacy and reduced side effects relative to TCAs and MAOIs. Though a debate remains regarding the exact mechanism by which the clinical efficacy of fluoxetine is manifested, the importance of fluoxetine and related SSRIs to the field is unquestionable. The trade name Prozac has permeated popular culture, helping to raise awareness of depression and to diminish the prevalence of long-standing stigmas associated with this illness. In this Review, we will showcase the history and importance of fluoxetine to neuroscience in general, as well as for the treatment of depression, and review the synthesis, pharmacology, drug metabolism, and adverse effects of fluoxetine.

  3. Fluoxetine versus sertraline in the treatment of patients with undifferentiated somatoform disorder: a randomized, open-label, 12-week, parallel-group trial.

    PubMed

    Han, Changsu; Pae, Chi-Un; Lee, Bun Hee; Ko, Young-Hoon; Masand, Prakash S; Patkar, Ashwin A; Jung, In-Kwa

    2008-02-15

    The present study was conducted to compare the effectiveness and tolerability of fluoxetine and sertraline in the treatment of undifferentiated somatoform disorder (USD), using the Patient Health Questionnaire (PHQ-15), which was specifically designed for assessing the severity of somatic symptoms. A randomized, 12-week, open-label trial of fluoxetine (10-60 mg/d) and sertraline (25-350 mg/d) in patients with USD was conducted. Six visits, at baseline and weeks 1, 2, 4, 8, and 12, were scheduled. Assessments for effectiveness and tolerability were conducted at each visit. The primary effectiveness measure was the mean change in PHQ-15 total score, from baseline to the end of treatment. Secondary effectiveness measures were the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ-12), from baseline to the end of treatment. A total of 45 subjects were enrolled; of them, 28 were randomly assigned to receive fluoxetine and 17 to receive sertraline. The total score on the PHQ-15 from baseline to the end of treatment significantly decreased in the fluoxetine (-10.7, p<0.0001) and sertraline (-10.3, p<0.0001) treatment groups, with no between-group difference (F=0.0701, p=0.7924). Overall, both treatments were well tolerated and no serious adverse event was reported. This study suggests that both agents may have a potential role in the treatment of USD. A double-blind, placebo-controlled trial and/or head-to-head comparison study with larger samples are required to draw more definite conclusions.

  4. Effects of Fluoxetine on Human Embryo Development

    PubMed Central

    Kaihola, Helena; Yaldir, Fatma G.; Hreinsson, Julius; Hörnaeus, Katarina; Bergquist, Jonas; Olivier, Jocelien D. A.; Åkerud, Helena; Sundström-Poromaa, Inger

    2016-01-01

    The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development. Human embryos (n = 48) were randomly assigned to treatment with 0.25 or 0.5 μM fluoxetine in culture medium. Embryo development was evaluated by time-lapse monitoring. The fluoxetine-induced human embryo proteome was analyzed by shotgun mass spectrometry. Protein secretion from fluoxetine-exposed human embryos was analyzed by use of high-multiplex immunoassay. The lower dose of fluoxetine had no influence on embryo development. A trend toward reduced time between thawing and start of cavitation was noted in embryos treated with 0.5 μM fluoxetine (p = 0.065). Protein analysis by shotgun mass spectrometry detected 45 proteins that were uniquely expressed in fluoxetine-treated embryos. These proteins are involved in cell growth, survival, proliferation, and inflammatory response. Culturing with 0.5 μM, but not 0.25 μM fluoxetine, caused a significant increase in urokinase-type plasminogen activator (uPA) in the culture medium. In conclusion, fluoxetine has marginal effects on the timing of developmental stages in embryos, but induces expression and secretion of several proteins in a manner that depends on dose. For these reasons, and in line with current guidelines, the lowest possible dose of SSRI should be used in pregnant women who need to continue treatment. PMID:27378857

  5. Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment

    PubMed Central

    Ding, Shengyuan; Li, Li

    2015-01-01

    The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1BRs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT1BRs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT1BRs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRI-based antidepressant treatment sensitizes this presynaptic 5-HT1BR-mediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment. PMID:25787955

  6. Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

    PubMed

    Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

    2016-02-01

    Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

  7. Altered water-maze search behavior in adult guinea pigs following chronic prenatal ethanol exposure: lack of mitigation by postnatal fluoxetine treatment.

    PubMed

    McAdam, Teresa D; Brien, James F; Reynolds, James N; Dringenberg, Hans C

    2008-08-22

    Ingestion of ethanol during pregnancy can result in teratogenic effects in humans, including significant and long-lasting neurobehavioral deficits. Similar results are seen in guinea pigs with chronic prenatal ethanol exposure (CPEE) via maternal ethanol administration, which produces deficits in Morris water-maze performance and impaired hippocampal functioning (e.g., decreased long-term potentiation, LTP). In this study, we tested whether postnatal treatment with fluoxetine, a selective serotonin reuptake inhibitor, decreases some of the neurobehavioral impairments produced by CPEE. Timed, pregnant guinea pigs received oral administration of ethanol (4g/kg maternal body weight) or isocaloric sucrose pair feeding (control) for 5 days/week throughout gestation. Offspring of the CPEE and control groups were randomly assigned to receive either fluoxetine (10mg/kg body weight/day) or saline intraperitoneally from postnatal day 10 to 48. Subsequent behavioral tests in the Morris water-maze revealed a significant increase in thigmotaxic swimming in CPEE offspring without apparent signs of impairment in spatial mapping of the hidden escape platform. Measures of hippocampal short- and long-term plasticity (paired-pulse facilitation, frequency facilitation, and LTP) were unaffected by CPEE, consistent with the behavioral data indicating normal hippocampal functioning. Postnatal fluoxetine administration resulted in a significant loss of body weight, but did not affect the increased thigmotaxic swimming following CPEE. These results indicate that changes in search strategies in the water-maze might be a highly sensitive index of CPEE-induced neurobehavioral toxicity that can occur in the absence of significant hippocampal dysfunction. Further, these data demonstrate that fluoxetine, at the selected treatment regime, does not mitigate the thigmotaxic swimming response to CPEE in the guinea pig.

  8. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    PubMed Central

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  9. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    PubMed

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

  10. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    PubMed

    Godavarthi, Swetha K; Dey, Parthanarayan; Sharma, Ankit; Jana, Nihar Ranjan

    2015-09-04

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural abnormalities is poorly understood. Here we have demonstrated significant impairment of adult hippocampal neurogenesis in AS mice brain. Although, the number of BrdU and Ki67-positive cell in the hippocampal DG region was nearly equal at early postnatal days among wild type and AS mice, they were significantly reduced in adult AS mice compared to wild type controls. Reduced number of doublecortin-positive immature neurons in this region of AS mice further indicated impaired neurogenesis. Unaltered BrdU and Ki67-positive cells number in the sub ventricular zone of adult AS mice brain along with the absence of imprinted expression of Ube3a in the neural progenitor cell suggesting that Ube3a may not be directly linked with altered neurogenesis. Finally, we show that the impaired hippocampal neurogenesis in these mice can be partially rescued by the chronic treatment of antidepressant fluoxetine. These results suggest that the chronic stress may lead to reduced hippocampal neurogenesis in AS mice and that impaired neurogenesis could contribute to cognitive disturbances observed in these mice.

  11. Comparison of the Addition of Siberian Ginseng (Acanthopanax senticosus) Versus Fluoxetine to Lithium for the Treatment of Bipolar Disorder in Adolescents: A Randomized, Double-Blind Trial

    PubMed Central

    Weng, Shenhong; Tang, Jihua; Wang, Gaohua; Wang, Xiaoping; Wang, Hui

    2007-01-01

    Background: Bipolar disorder (BD) is a common, recurrent, and often life-long major psychiatric condition characterized by manic, depressive, and mixed episodes. Without treatment, there is substantial risk for morbidity and mortality, making BD a considerable public health problem. Objective: The purpose of this study was to compare the relative effectiveness and tolerability of Acanthopanax senficosus (A senficosus)—an herb that is derived from eleutherosides and polysaccharides found in the plant's root— versus fluoxetine added to lithium in the treatment of BD in adolescents. Methods: This was a double-blind, 6-week study. The patients were randomized into 2 treatment groups—A senticosus plus lithium (A senticosus group) and fluoxetine plus lithium (fluoxetine group). The patients underwent a baseline assessment using the 17-Item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) during the screening period. Patients were scheduled for clinical visits at the end of weeks 1, 2, 4, and 6. At the end of the 6-week treatment period, each patient's condition was rated as follows: response (indicating an improvement of ≥50% in the HAMD-17 score from baseline); remission (a HAMD-17 score of ⪯7); and switching to mania (a YMRS score >16, and meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] for a manic episode). At each visit (with the exception of the enrollment visit), the patients were queried as to whether they experienced any health problems since the previous visit, a Treatment Emergent Symptom Scale assessment was completed, and the serum lithium concentration was analyzed. The patients were instructed to report adverse events (AEs) at any time during the study. AEs were also observed by the investigator(s) at clinical visits. Results: Seventy-nine Chinese adolescents were initially enrolled into the study. However, 76 adolescents were assessed for inclusion

  12. Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions.

    PubMed

    Romero-Reyes, Jessica; Cárdenas, Mario; Damián-Matsumura, Pablo; Domínguez, Roberto; Ayala, María Elena

    2016-01-01

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor is an antidepressant in the treatment of mood disorders. Its impact on reproductive processes is incompletely known. The present study analyzed the reproductive effects of FLX in prepubertal female rats. Two experiments were conducted. First (acute administration), 30-day-old female rats were injected intraperitoneally with 5mg/kg of fluoxetine-hydrochloride, and were terminated 24, 48 or 72h after the treatment. Second (subchronic administration), FLX was injected on days 30-33 of age, and the animals were terminated the day of first estrus. In acute treatment estradiol concentration increased to 72h. In subchronic treatment increased serotonin concentration in ovaries and decreased the number of ova shed. An increase in number of atretic follicles and oocyte fragmentation was observed in these animals. The results suggest that FLX acts on the ovary or hypothalamus-pituitary axis resulting in modifications of the follicular development and ovulation.

  13. Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: effects of chronic fluoxetine treatment.

    PubMed

    Zarate, J; Churruca, I; Echevarría, E; Casis, L; López de Jesús, M; Saenz del Burgo, L; Sallés, J

    2008-10-21

    In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB1 cannabinoid receptor to define the expression of the neural CB1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated receptor (CB1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.

  14. Higher levels of aggression are observed in socially dominant toadfish treated with the selective serotonin reuptake inhibitor, fluoxetine.

    PubMed

    McDonald, M Danielle; Gonzalez, Alexander; Sloman, Katherine A

    2011-01-01

    The following study set out to test the hypothesis that acute treatment with the selective serotonin reuptake inhibitor, fluoxetine, would result in a rise in circulating 5-HT levels and consequently a decrease in territorial aggression in the Gulf toadfish, Opsanus beta. Size-matched pairs of toadfish were implanted intraperitoneally with the same dose of fluoxetine (0, 10 or 25 μg g⁻¹). After a social interaction between a pair of fish, circulating levels of serotonin (5-HT; 5-hydroxytryptamine) and cortisol were measured and relative mRNA expression of the 5-HT(1A) receptor in the toadfish brain was determined using quantitative (real-time) PCR (qPCR). Behavioral endpoints such as the number of aggressive acts and swimming activity were also quantified so that dominant and subordinate fish could be identified. Fluoxetine treatment resulted in an increase in circulating levels of 5-HT, regardless of social status. Circulating cortisol concentrations were unaffected by fluoxetine, but were significantly higher in subordinate individuals when compared to dominant fish. Toadfish brain 5-HT(1A) receptor mRNA expression was not affected by treatment or social status. Lastly and contrary to our predictions, fluoxetine treatment resulted in an increase in the number of aggressive acts made by dominant individuals, with no differences in the level of aggression or swimming activity of subordinate fish. This study is the first to describe elevated aggression in a teleost fish with elevated circulating levels of 5-HT.

  15. Side effects after phototherapy implementation in addition to fluoxetine or sertraline treatment: a report of two cases.

    PubMed

    Swiecicki, Łukasz; Szafrański, Tomasz

    2002-04-01

    Serotonergic-type side effects (like diarrhoea, hyperthermia, nausea, confusion) were seen after phototherapy in patients receiving fluoxetine or sertraline. Phototherapy was discontinued and symptoms completely resolved. In the authors' opinion, the symptoms were likely to be associated with specific interaction (serotonin effect potentialisation). To the authors' knowledge this is the first report concerning such an effect.

  16. Initial Steps to inform selection of continuation cognitive therapy or fluoxetine for higher risk responders to cognitive therapy for recurrent major depressive disorder.

    PubMed

    Vittengl, Jeffrey R; Anna Clark, Lee; Thase, Michael E; Jarrett, Robin B

    2017-03-22

    Responders to acute-phase cognitive therapy (A-CT) for major depressive disorder (MDD) often relapse or recur, but continuation-phase cognitive therapy (C-CT) or fluoxetine reduces risks for some patients. We tested composite moderators of C-CT versus fluoxetine's preventive effects to inform continuation treatment selection. Responders to A-CT for MDD judged to be at higher risk for relapse due to unstable or partial remission (N=172) were randomized to 8 months of C-CT or fluoxetine with clinical management and assessed, free from protocol treatment, for 24 additional months. Pre-continuation-treatment characteristics that in survival analyses moderated treatments' effects on relapse over 8 months of continuation-phase treatment (residual symptoms and negative temperament) and on relapse/recurrence over the full observation period's 32 months (residual symptoms and age) were combined to estimate the potential advantage of C-CT versus fluoxetine for individual patients. Assigning patients to optimal continuation treatment (i.e., to C-CT or fluoxetine, depending on patients' pre-continuation-treatment characteristics) resulted in absolute reduction of relapse or recurrence risk by 16-21% compared to the other non-optimal treatment. Although these novel results require replication before clinical application, selecting optimal continuation treatment (i.e., personalizing treatment) for higher risk A-CT responders may decrease risks of MDD relapse and recurrence substantively.

  17. Prolonged running, not fluoxetine treatment, increases neurogenesis, but does not alter neuropathology, in the 3xTg mouse model of Alzheimer's disease.

    PubMed

    Marlatt, Michael W; Potter, Michelle C; Bayer, Thomas A; van Praag, Henriette; Lucassen, Paul J

    2013-01-01

    Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we tested whether activity and pharmacological stimulation could prevent memory deficits and modify neurogenesis and/or neuropathology in the 3xTg model backcrossed to the C57Bl/6 strain. We chronically administered the antidepressant fluoxetine to one group of mice, allowed access to a running wheel in another, and combined both treatments in a third cohort. All treatments lasted for 11 months. The female 3xTg mice failed to exhibit any deficits in spatial learning and memory as measured in the Morris water maze, indicating that when backcrossed to the C57Bl/6 strain, the 3xTg mice lost the behavioral phenotype that was present in the original 3xTg mouse maintained on a hybrid background. Despite this, the backcrossed 3xTg mice expressed prominent intraneuronal amyloid beta (Aβ) levels in the cortex and amygdala, with lower levels in the CA1 area of the hippocampus. In the combined cohort, fluoxetine treatment interfered with exercise and reduced the total distance run. The extent of Aβ neuropathology, the tau accumulations, or BDNF levels, were not altered by prolonged exercise. Thus, neuropathology was present but not paralleled by spatial memory deficits in the backcrossed 3xTg mouse model of AD. Prolonged exercise for 11 months did improve the long-term survival of newborn neurons generated during middle-age, whereas fluoxetine had no effect. We further review and discuss the relevant literature in this respect.

  18. 12-Month Follow-Up of Fluoxetine and Cognitive Behavioral Therapy for Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Crosby, Ross D.; Wilson, G. Terence; Masheb, Robin M.

    2012-01-01

    Objective: The longer term efficacy of medication treatments for binge-eating disorder (BED) remains unknown. This study examined the longer term effects of fluoxetine and cognitive behavioral therapy (CBT) either with fluoxetine (CBT + fluoxetine) or with placebo (CBT + placebo) for BED through 12-month follow-up after completing treatments.…

  19. Anaphylaxis: acute treatment and management.

    PubMed

    Ring, Johannes; Grosber, Martine; Möhrenschlager, Matthias; Brockow, Knut

    2010-01-01

    Anaphylaxis is the maximal variant of an acute life-threatening immediate-type allergy. Due to its often dramatic onset and clinical course, practical knowledge in the management of these reactions is mandatory both for physicians and patients. It has to be distinguished between acute treatment modalities and general recommendations for management of patients who have suffered from an anaphylactic reaction. Acute treatment comprises general procedures like positioning, applying an intravenous catheter, call for help, comfort of the patient as well as the application of medication. The acute treatment modalities are selected depending upon the intensity of the clinical symptomatology as they are categorized in 'severity grades'. First of all it is important to diagnose anaphylaxis early and consider several differential diagnoses. This diagnosis is purely clinical and laboratory tests are of no help in the acute situation. Epinephrine is the essential antianaphylactic drug in the pharmacologic treatment. It should be first applied intramuscularly, only in very severe cases or under conditions of surgical interventions intravenous application can be tried. Furthermore, glucocorticosteroids are given in order to prevent protracted or biphasic courses of anaphylaxis; they are of little help in the acute treatment. Epinephrine autoinjectors can be used by the patient him/herself. Histamine H(1)-antagonists are valuable in mild anaphylactic reactions; they should be given intravenously if possible. The replacement of volume is crucial in antianaphylactic treatment. Crystalloids can be used in the beginning, in severe shock colloid volume substitutes have to be applied. Patients suffering from an anaphylactic episode should be observed over a period of 4-10 h according to the severity of the symptomatology. It is crucial to be aware or recognize risk patients as for example patients with severe uncontrolled asthma, or under beta-adrenergic blockade. When bronchial

  20. Methamphetamine and fluoxetine treatment of a child with attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

    PubMed

    Bussing, R; Levin, G M

    1993-01-01

    ABSTRACT An 11-year-old child with obsessive-compulsive disorder, major depression, and attentiondeficit hyperactivity disorder was successfully treated with a combination of fluoxetine (mean 30 mg daily) and methamphetamine (sustained release 10 mg daily). Methamphetamine was selected because of the desirability of avoiding stimulants whose commercial formulations contain food dyes (this child appeared sensitive to tartrazine in dextroamphetamine and other agents), whose effects on hepatic metabolism were minimal (unlike methylphenidate) and whose mechanism of action is reliably rapid (unlike pemoline). Although methamphetamine carries the stigma of an abusable drug and has been implicated in neurotoxicity in animals when used at extremely high doses, methamphetamine may have certain advantages over other psychostimulants in some clinical situations. The combined use of fluoxetine and methamphetamine did not appear to be associated with significant adverse effects.

  1. Effects of fluoxetine on the oxidative status of peripheral blood leucocytes of restraint-stressed mice.

    PubMed

    Novío, Silvia; Núñez, María Jesús; Amigo, Gonzalo; Freire-Garabal, Manuel

    2011-11-01

    Emotional stress can be viewed as a cause of adverse circumstances that induces a wide range of biochemical and behavioural changes. Oxidative stress is a critical route of damage in various psychological stress-induced disorders such as depression. Antidepressants are widely prescribed to treat these conditions; however, no animal study has investigated the effect of selective serotonin reuptake inhibitors (SSRIs) on the levels of intracellular reactive oxygen species in peripheral blood leucocytes of stressed mice. In this study, mice were immobilized for a period of 6 hr. Fluoxetine (5 mg/kg of body-weight) was administered 30 min. before subjecting the animals to acute stress. The level of intracellular reactive oxygen species in leucocytes of the peripheral blood of stressed mice was investigated using a 2',7'-dichlorofluorescein diacetate probe, and the antioxidant response of fluoxetine was evaluated by superoxide dismutase, diaphorase, catalase and reduced glutathione. Our results show that restraint stress significantly increases the generation of reactive oxygen species in the peripheral defence cells. Treatment with fluoxetine partially reverses the adverse effects of stress. The improvement in cellular oxidative status may be an important mechanism underlying the protective pharmacological effects of fluoxetine, which are clinically observed in the treatment of depressive disorders.

  2. The treatment of acute vertigo.

    PubMed

    Cesarani, A; Alpini, D; Monti, B; Raponi, G

    2004-03-01

    Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière's disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v., 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or triethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internuclear inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20 degrees. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different

  3. Dual effects of fluoxetine on mouse early embryonic development

    SciTech Connect

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  4. Treatment of acute septic arthritis.

    PubMed

    Pääkkönen, Markus; Peltola, Heikki

    2013-06-01

    Acute septic arthritis is a rare, but potentially devastating disease. The treatment is initiated intravenously, but can be safely switched to oral after 2-4 days providing large doses of a well-absorbing antibiotic and, for time-dependent antibiotics, 4 times-a-day administration are used. Empiric treatment should always cover Staphylococcus aureus and common respiratory pathogens, whereas Kingella kingae and Salmonella are important only regionally. Studies conducted by our group have shown that a total course of 10 days may suffice for previously healthy children in a Western setting. Treatment of neonates, patients with immunodeficiency or cases caused by methicillin-resistant S. aureus, may deserve a different approach.

  5. Diazepam and Fluoxetine Decrease the Stress Response in Zebrafish

    PubMed Central

    de Abreu, Murilo Sander; Koakoski, Gessi; Ferreira, Daiane; Oliveira, Thiago Acosta; da Rosa, João Gabriel Santos; Gusso, Darlan; Giacomini, Ana Cristina Varrone; Piato, Angelo Luis; Barcellos, Leonardo José Gil

    2014-01-01

    The presence of pharmaceutical products in the aquatic environment has been reported in several studies. However, the impact of these drugs on living organisms is still uncharacterized. Here, we investigated the effects of acute exposure to either diazepam or fluoxetine on the stress response in Danio rerio. We showed that diazepam and fluoxetine inhibited the stress axis in zebrafish. Intermediate concentrations of diazepam suppressed the stress response as measured by cortisol levels, whereas fluoxetine inhibited cortisol increase at concentrations similar to those found in the environment. These data suggest that the presence of psychoactive drugs in aquatic ecosystems could cause neuroendocrine dysfunction in fish. PMID:25054216

  6. Phaeochromocytoma unearthed by fluoxetine

    PubMed Central

    Kashyap, A

    2000-01-01

    Non-specific noradrenaline reuptake inhibition by high dose selective serotonin reuptake inhibitors, along with catecholamine release from phaeochromocytoma, may lead to a hypertensive paroxysm. This may unmask a clinically silent phaeochromocytoma. Hypertensive paroxysm induced by paroxetine leading to detection of phaeochromocytoma has been reported. The first patient in whom fluoxetine unmasked a phaeochromocytoma is reported.


Keywords: selective serotonin reuptake inhibitor; fluoxetine; phaeochromocytoma PMID:10775287

  7. Fluoxetine tenth anniversary update: the progress continues.

    PubMed

    Stokes, P E; Holtz, A

    1997-01-01

    This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depression, patients with eating disorders, and patients with obsessive-compulsive disorder (OCD); its long-term (maintenance) efficacy; its side effects and toxicity; and pharmacoeconomic considerations are reviewed. Pharmacotherapy is currently the only proven method for treating major depressive disorder that is applicable to all levels of severity of major depressive illness. Since its introduction 10 years ago, fluoxetine has been available to psychiatrists, primary care physicians, and other nonpsychiatric physicians as full-dose effective pharmacotherapy for patients with depression. Fluoxetine has been widely prescribed by physicians knowledgeable in pharmacology and in the treatment of depression because of its proven efficacy (ie, equal to that of tricyclic antidepressants [TCAs]), its ease of administration (with full therapeutic dosing usually starting from day 1), its generally benign side-effect profile, its remarkable safety in over-dose, and its proven effectiveness in the most common depressed patient population--anxious, agitated, depressed patients--as well as in patients with various subtypes and severities of depression. In more recent years it has also proved effective in the treatment of bulimia, an entity for which only limited or inadequate treatment options had been previously available. In OCD, fluoxetine, with its more acceptable side-effect profile and greater ease of dosing, presents a favorable alternative to previous drug therapy and is useful in treating both obsessions and compulsions. Fluoxetine is currently recognized among clinicians as efficacious in treating anxiety disorders and is being used successfully in special

  8. Fluoxetine and the mitochondria: A review of the toxicological aspects.

    PubMed

    de Oliveira, Marcos Roberto

    2016-09-06

    Fluoxetine (a selective serotonin reuptake inhibitor (SSRI)) is used as an antidepressant by modulating the levels of serotonin in the synaptic cleft. Nevertheless, fluoxetine also induces undesirable effects, such as anxiety, sexual dysfunction, sleep disturbances, and gastrointestinal impairments. Fluoxetine has been viewed as an agent that may interfere with cell fate by triggering apoptosis. On the other hand, fluoxetine intake has been associated with increased cancer risk. Nonetheless, data remain contradictory and no conclusions were taken. Several studies demonstrated that fluoxetine interacts with mitochondria triggering apoptosis and/or altering mitochondrial function by modulating the activity of respiratory chain components and enzymes of the Krebs cycle. Furthermore, fluoxetine affects mitochondria-related redox parameters in different experimental models. In this review, data demonstrating the effects of fluoxetine upon mammalian mitochondria are described and discussed, as well as several unsolved questions in this field of research are addressed. A separate section deals with future needs regarding the research involving the impact of fluoxetine treatment upon mitochondria and mitochondria-related signaling.

  9. Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress.

    PubMed

    Moretti, Morgana; Colla, André; de Oliveira Balen, Grasiela; dos Santos, Danúbia Bonfanti; Budni, Josiane; de Freitas, Andiara Espíndola; Farina, Marcelo; Severo Rodrigues, Ana Lúcia

    2012-03-01

    Reactive oxygen species (ROS) have been shown to play a role in the pathophysiology of depression. Taking into account that experimental chronic unpredictable stress (CUS) induces depressive-like behavior and that ascorbic acid has antidepressant-like effect in animals, the objective of this study was to investigate the influence of ascorbic acid on depressive-like behavior induced by CUS paradigm, serum corticosterone levels and markers of oxidative stress in cerebral cortex and hippocampus of mice. Animals were submitted to CUS procedure during 14 days. From the 8th to the 14th day mice received ascorbic acid (10 mg/kg) or fluoxetine (10 mg/kg, conventional antidepressant, positive control) once a day by oral route. On 15th day behavioral and biochemical parameters were analyzed. CUS exposure caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test and decreased time in which mice spent grooming in the splash test. Depressive-like behavior induced by CUS was accompanied by a significant increased lipid peroxidation (cerebral cortex and hippocampus), decreased catalase (CAT) (cerebral cortex and hippocampus) and glutathione reductase (GR) (hippocampus) activities and reduced levels of glutathione (cerebral cortex). Repeated ascorbic acid or fluoxetine administration significantly reversed CUS-induced depressive-like behavior and oxidative damage. No alteration was observed in locomotor activity, corticosterone levels and glutathione peroxidase (GPx) activity. These findings indicate a rapid and robust effect of ascorbic acid in reversing behavioral and biochemical alterations induced by CUS in mice, suggesting that this vitamin may be an alternative approach for the management of depressive symptoms.

  10. Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

    PubMed Central

    2012-01-01

    Background Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents. Results We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of middle-aged (8 months old) rats. The density of puncta expressing PSA-NCAM increased in the dorsal cingulate cortex, as well as in different hippocampal and amygdaloid regions. In these later regions there were also increases in the density of puncta expressing glutamic acid decarboxylase 65/67 (GAD6), synaptophysin (SYN), PSA-NCAM/SYN and PSA-NCAM/GAD6, but a decrease of those expressing vesicular glutamate transporter 1 (VGluT1). Since there is controversy on the effects of antidepressants on neurogenesis during aging, we analyzed the number of proliferating cells expressing Ki67 and that of immature neurons expressing doublecortin or PSA-NCAM. No significant changes were found in the subgranular zone, but the number of proliferating cells decreased in the subventricular zone. Conclusions These results indicate that the effects of fluoxetine in middle-aged rats are different to those previously described in young-adult animals, being more restricted in the mPFC and even following an opposite direction in the amygdala or the subventricular zone. PMID:22221403

  11. Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

    PubMed Central

    Mischoulon, David; Lamon-Fava, Stefania; Selhub, Jacob; Katz, Judith; Papakostas, George I.; Iosifescu, Dan V.; Yeung, Albert S.; Dording, Christina M.; Farabaugh, Amy H.; Clain, Alisabet J.; Baer, Lee; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio

    2014-01-01

    Objective To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. Methods We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20–60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined. Results Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C=41%, C/T=47%, T/T=11%, A/A=66%, A/G=29%, G/G=4%). In the fluoxetine-treated subsample (n=49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response. Conclusion The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples. PMID:22789065

  12. Effects of trazodone and fluoxetine in the treatment of major depression: therapeutic pharmacokinetic and pharmacodynamic interactions through formation of meta-chlorophenylpiperazine.

    PubMed

    Maes, M; Westenberg, H; Vandoolaeghe, E; Demedts, P; Wauters, A; Neels, H; Meltzer, H Y

    1997-10-01

    It has been suggested that (1) the clinical efficacy of the heterocyclic antidepressant trazodone in depression may, in part, be attributed to its metabolite meta-chlorophenylpiperazine (mCPP); and (2) the enhancement of the efficacy of trazodone by the addition of fluoxetine, a selective serotonin reuptake inhibitor, may, in part, be ascribed to fluoxetine-induced plasma concentrations of trazodone. After a washout period of 10 days, 27 inpatients with major depression were treated with trazodone 100 mg/day (orally). One week later (T0), fluoxetine 20 mg/day, placebo, or pindolol 7.5 mg/day was added. Plasma concentrations of mCPP and trazodone were determined at T0 and 2 and 4 weeks later. Although placebo pindolol had no significant effect on the plasma concentrations of mCPP and trazodone, there was a significant increase of the concentrations of these compounds associated with the combination of trazodone + fluoxetine. The results suggest that fluoxetine-induced increases in plasma mCPP and trazodone concentrations contribute to the clinical efficacy of the combination of fluoxetine + trazodone. It is suggested that desensitization of 5-HT2C receptor function by mCPP as well as fluoxetine may contribute to the antidepressant effects of this combination.

  13. [Pharmacological treatment of acute catatonia].

    PubMed

    Cárdenas-Delgado, Christian L

    2012-01-01

    Catatonia is a neuropsychiatric syndrome of psychomotor dysregulation that can be present in a broad spectrum of clinical situations. Advances made over the last decades have progressively contributed to its clinical differentiation and its conceptual delimitation. Both Benzodiazepines (BZD) and Electroconvulsive therapy (ECT) have been consolidated as first-line therapy. In this regard, a BZD response rate ranging from 70 to 90 per cent has been reported in different case series. Furthermore, NMDA receptor antagonists represent an emerging strategy in the therapeutic approach to the disorder. Most of the evidence that supports the aforementioned treatment recommendations arises from descriptive observational studies. Traditionally, catatonia pathophysiological research focused on the study of subcortical brain structures. Currently there exists compelling evidence that supports a cortical origin of the syndrome, emphasizing the role of the prefrontal cortex. Neuropsychiatric catatonia models that integrate clinical, pathophysiological, and neurobiological findings have been postulated. The aim of the present review is to summarize up-to-date available evidence associated with the pharmacotherapeutic approach to acute catatonia as well as the neurochemical basis of its effectiveness. Likewise, general measures intended to prevent morbimortality are subject to discussion herein.

  14. Fluoxetine and sertraline dosages in major depression.

    PubMed

    Cantrell, R; Gillespie, W; Altshuler, L

    1999-01-01

    In a retrospective study, we sought to determine medication dosages usually prescribed to obtain euthymia in 59 outpatients with a diagnosis of major depression treated with fluoxetine or sertraline. Charts of veterans admitted to the outpatient mental health clinic at the West Los Angeles Veterans Hospital with a diagnosis of major depression and treated with either fluoxetine or sertraline were reviewed. Progress notes were analyzed for a 6-month time period after the initiation of the medication treatment, and improvement was rated by a physician blind to the drug used for treatment. No significant differences were found in overall response rates between the fluoxetine (81% responders) and sertraline (76% responders) groups. Eighty-one percent of the fluoxetine responders compared to 32% of sertraline responders were at the manufacturer's recommended starting dose (MRSD) at the time of clinical response. One-third of patients receiving sertraline were started on or rapidly titrated to more than 50 mg/day. When only those patients receiving an adequate trial of sertraline at 50 mg were considered, 47% required a dose increase to achieve a remission. These data suggest that 50 mg of sertraline may be inadequate for some patients to achieve a resolution of symptoms of major depression and that many clinicians currently prescribe in a manner suggesting that they believe the MRSD is a suboptimal dosage.

  15. Intermittent amantadine for fluoxetine-induced anorgasmia.

    PubMed

    Balon, R

    1996-01-01

    Various drugs, including amantadine, have been reported in the successful treatment of antidepressant-induced sexual dysfunction. Only a regular daily dosing schedule of amantadine has been used for the treatment of sexual dysfunction so far. This case demonstrates that an intermittent dose of amantadine at 100 mg five to six hours prior to coitus could be useful in the treatment of fluoxetine-induced anorgasmia.

  16. Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Macías-Cortés, Emma del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

    2015-01-01

    Background Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo

  17. Fluoxetine Inhibits NLRP3 Inflammasome Activation: Implication in Depression

    PubMed Central

    Du, Ren-Hong; Tan, Jun; Sun, Xi-Yang; Lu, Ming; Ding, Jian-Hua

    2016-01-01

    Background: Emerging evidence indicates that NLRP3 inflammasome-induced inflammation plays a crucial role in the pathogenesis of depression. Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of depression. Fluoxetine, a widely used antidepressant, has been shown to have potential antiinflammatory activity, but the underlying mechanisms remain obscure. Methods: We used a chronic mild stress model and cultured primary macrophage/microglia to investigate the effects of fluoxetine on NLRP3 inflammasome and its underlying mechanisms. Results: We demonstrated that fluoxetine significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1β secretion in both peripheral macrophages and central microglia. We further found that fluoxetine reduced reactive oxygen species production, attenuated the phosphorylation of double-stranded RNA-dependent protein kinase, and inhibited the association of protein kinase with NLRP3. These data indicate that fluoxetine inhibits the activation of NLRP3 inflammasome via downregulating reactive oxygen species-protein kinase-NLRP3 signaling pathway. Correspondingly, in vivo data showed that fluoxetine also suppressed NLRP3 inflammasome activation in hippocampus and macrophages of chronic mild stress mice and alleviated chronic mild stress-induced depression-like behavior. Conclusions: Our findings reveal that fluoxetine confers an antidepressant effect partly through inhibition of peripheral and central NLRP3 inflammasome activation and suggest the potential clinical use of fluoxetine in NLRP3 inflammasome-driven inflammatory diseases such as depression. PMID:27207922

  18. Fluoxetine attenuates alcohol intake and desire to drink.

    PubMed

    Naranjo, C A; Poulos, C X; Bremner, K E; Lanctot, K L

    1994-09-01

    Several serotonin uptake inhibitors, including the long-acting fluoxetine, have been found to decrease alcohol intake in moderately dependent alcoholics. While the mechanism of their effect is not fully elucidated, a previous study with citalopram indicated that decreased desire to drink may be an important factor. Therefore, we tested fluoxetine effects on alcohol intake and desire to drink in a placebo-controlled study. Subjects, recruited by advertisement, were mildly/moderately dependent alcoholics (12 male, four female, aged 19-59 years, healthy, non-depressed) who did not believe they had a drinking problem and were not requesting treatment. After a 1 week baseline they received, single-blind, 2 weeks placebo followed by 2 weeks fluoxetine 60 mg/day. As out-patients, subjects recorded daily standard drinks (13.6 g ethanol) and rated interest, desire, craving and liking for alcohol biweekly. Each out-patient period was immediately followed by a double-blind experimental drinking session. Out-patient daily drinks slightly decreased during fluoxetine to 6.6 +/- 0.9 (mean +/- S.E.M.) compared with during placebo (7.16 +/- 0.95, p = 0.07, N.S.) and baseline (7.18 +/- 1.0, p > 0.1, N.S.). Desire, interest and craving for alcohol decreased during fluoxetine vs placebo baseline (p < 0.05), but not vs placebo. Appetite loss and decrease in food intake (p < 0.01, fluoxetine vs placebo) correlated with each other (r = 0.91, p < 0.01) but neither correlated with decrease in alcohol intake (appetite: r = 0.26, N.S.; food intake: r = 0.22, N.S.). Weight loss occurred during fluoxetine (p < 0.05 vs placebo) but did not correlate with decrease in alcohol intake (r = 0.1, N.S.). In the experimental drinking sessions after placebo and fluoxetine treatments subjects rated their desire for each of 18 mini-drinks (each one-third of a standard drink) offered at 5 min intervals. Fluoxetine decreased desire to drink throughout the sessions; both mean and maximum desire ratings were

  19. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  20. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  1. A Systematic Review of the Evidence for the Treatment of Acute Depression in Bipolar I Disorder

    PubMed Central

    Cerullo, Michael A.; Strakowski, Stephen M.

    2013-01-01

    In this article we examined evidence for the acute treatment of depression in bipolar I disorder, focusing on double-blind, placebo-controlled studies with a definite primary outcome measure and published in peer review journals. Quetiapine and olanzapine/fluoxetine are currently approved by the FDA for the treatment of bipolar depression and a number of additional agents (including other atypical antipsychotics, mood stabilizers, antidepressants, and novel compounds) have been studied with varying degrees of efficacy. The medication with the most evidence for efficacy in bipolar depression is quetiapine with five studies showing positive efficacy compared to placebo. In contrast five studies of lamotrigine were negative although meta-analyses of the pooled have found some treatment effects. Two studies of olanzapine and olanzapine/fluoxetine and three small studies of divalproex showed significant efficacy in treating bipolar depression. Two studies of aripiprazole found no differences compared to placebo. Early research on lithium in bipolar depression had significant methodological flaws and only one study of lithium met our primary search criteria. To better understand the role of anti-depressants we also examined studies of antidepressants as adjunctive treatment of bipolar depression in participants taking mood stabilizers or atypical antipsychotics. These studies reported mixed results for a variety of antidepressants but the majority found no differences compared to placebo. Other studies of adjunctive treatment were also discussed. There has been one positive adjunctive study each of lamotrigine, omega-3 fatty acids, modafinil, and Armodafinil while there was one negative trial each of omega-3 fatty acids, ziprasidone, and levetiracetam. PMID:23507138

  2. A systematic review of the evidence for the treatment of acute depression in bipolar I disorder.

    PubMed

    Cerullo, Michael A; Strakowski, Stephen M

    2013-08-01

    In this article, we examined evidence for the acute treatment of depression in bipolar I disorder, focusing on double-blind, placebo-controlled studies with a definite primary outcome measure and published in peer review journals. Quetiapine and olanzapine/fluoxetine are currently approved by the FDA for the treatment of bipolar depression, and a number of additional agents (including other atypical antipsychotics, mood stabilizers, antidepressants, and novel compounds) have been studied with varying degrees of efficacy. The medication with the most evidence for efficacy in bipolar depression is quetiapine, with five studies showing positive efficacy compared to placebo. In contrast, five studies of lamotrigine were negative, although meta-analyses of the pooled have found some treatment effects. Two studies of olanzapine and olanzapine/fluoxetine and three small studies of divalproex showed significant efficacy in treating bipolar depression. Two studies of aripiprazole found no differences compared to placebo. Early research on lithium in bipolar depression had significant methodological flaws, and only one study of lithium met our primary search criteria. To better understand the role of antidepressants, we also examined studies of antidepressants as adjunctive treatment of bipolar depression in participants taking mood stabilizers or atypical antipsychotics. These studies reported mixed results for a variety of antidepressants, but the majority found no differences compared to placebo. Other studies of adjunctive treatment were also discussed. There has been one positive adjunctive study each of lamotrigine, omega-3 fatty acids, modafinil, and armodafinil, while there was one negative trial each of omega-3 fatty acids, ziprasidone, and levetiracetam.

  3. Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure

    DTIC Science & Technology

    2012-07-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Although selective serotonin reuptake inhibitors (SSRIs) are routinely prescribed for acute stress disorder and early PTSD...8 Supporting Data…………………………………………………………………. 4 INTRODUCTION: Although selective serotonin reuptake ... inhibitors (SSRIs) are routinely prescribed for acute stress disorder and early PTSD and recommended in the VA-DoD best practice guidelines, the efficacy

  4. Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia.

    PubMed

    Myung, Chang-Seon; Kim, Bom-Taeck; Choi, Si Ho; Song, Gyu Yong; Lee, Seok Yong; Jahng, Jeong Won

    2005-06-01

    Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC (alpha-MSH).

  5. Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression.

    PubMed

    Sakr, H F; Abbas, A M; Elsamanoudy, A Z; Ghoneim, F M

    2015-08-01

    Our objective was to investigate the effects of chronic unpredictable mild stress (CUMS) with or without selective serotonin reuptake inhibitor (fluoxetine) and anti-oxidant (resveratrol) on testicular functions and oxidative stress in rats. Fifty male rats were divided into 2 groups; control and CUMS. CUMS group was further subdivided into 4 subgroups administered water, fluoxetine, resveratrol and both. Sucrose intake, body weight gain, serum corticosterone, serotonin and testosterone levels, sperm count and motility, testicular malondialdehyde, superoxide dismutase (SOD), catalase, glutathione (GSH), and gene expression of steroidogenic acute-regulatory (StAR) protein and cytochrome P450 side chain cleavage (P450scc) enzyme were evaluated. CUMS decreased sucrose intake, weight gain, anti-oxidants (SOD, catalase, GSH), testosterone, serotonin, StAR and cytochrome P450scc gene expression, sperm count and motility and increased malondialdehyde and corticosterone. Fluoxetine increased malondialdehyde, sucrose intake, weight gain, serotonin and decreased anti-oxidants, StAR and cytochrome P450scc gene expression, sperm count and motility, testosterone, corticosterone in stressed rats. Administration of resveratrol increased anti-oxidants, sucrose intake, weight gain, serotonin, StAR and cytochrome P450scc gene expression, testosterone, sperm count and motility, and decreased malondialdehyde and corticosterone in stressed rats with or without fluoxetine. In conclusion, CUMS induces testicular dysfunctions and oxidative stress. While treatment of CUMS rats with fluoxetine decreases the depressive behavior, it causes further worsening of testicular dysfunctions and oxidative stress. Administration of resveratrol improves testicular dysfunctions and oxidative stress that are caused by CUMS and further worsened by fluoxetine treatment.

  6. Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine.

    PubMed

    Rodríguez-Gaztelumendi, Antonio; Rojo, M Luisa; Pazos, Angel; Díaz, Alvaro

    2009-03-01

    Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB(1) receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.

  7. Pharmacokinetics/pharmacodynamics of desloratadine and fluoxetine in healthy volunteers.

    PubMed

    Gupta, Samir; Banfield, Christopher; Kantesaria, Bhavna; Flannery, Brian; Herron, Jerry

    2004-11-01

    The authors assessed the potential for a pharmacokinetic/pharmacodynamic interaction between desloratadine and fluoxetine. This randomized, placebo-controlled, open-label study was conducted in 54 healthy volunteers. Subjects received 1 of 3 treatments: desloratadine 5 mg plus fluoxetine 20 mg, desloratadine 5 mg plus placebo, or fluoxetine 20 mg plus placebo. Serial electrocardiograms (ECGs) were performed at baseline and day 35. Treatment effects on C(max) and AUC were assessed. During coadministration of desloratadine with fluoxetine, the ratio of the mean log-transformed C(max) and AUC values for desloratadine following concomitant fluoxetine therapy revealed a small increase in C(max) values of 15% (90% confidence interval [CI], 95%-139%) but no increase for AUC values (90% CI, 82%-123%). Corresponding values for 3-OH desloratadine demonstrated small increases in mean log-transformed C(max) and AUC ratios: 17% (90% CI, 100%-136%) and 13% (90% CI, 96%-132%), respectively. Statistical evaluation of the ratio of the mean C(max) and AUC values for fluoxetine following concomitant desloratadine therapy revealed small decreases of 9% (90% CI, 72%-115%) and 11% (90% CI, 69%-113%), respectively. Corresponding values for norfluoxetine demonstrated modest increases in mean log-transformed C(max) and AUC ratios: 22% (90% CI, 100%-139%) and 18% (90% CI, 101%-136%), respectively. Coadministration of desloratadine with a potent inhibitor of CYP2D6 did not result in clinically relevant changes in its pharmacokinetic parameters. Desloratadine administration was not associated with clinically important changes in the pharmacokinetics of fluoxetine, a drug metabolized by CYP2D6. The most common adverse event in all groups was headache (65%). Desloratadine plus fluoxetine caused no significant changes in ECGs or ventricular rate.

  8. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  9. Chronic Treatment with the IDO1 Inhibitor 1-Methyl-D-Tryptophan Minimizes the Behavioural and Biochemical Abnormalities Induced by Unpredictable Chronic Mild Stress in Mice - Comparison with Fluoxetine

    PubMed Central

    Laugeray, Anthony; Launay, Jean-Marie; Callebert, Jacques; Mutlu, Oguz; Guillemin, Gilles J.; Belzung, Catherine; Barone, Pascal R.

    2016-01-01

    We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure—a validated model of stress-induced depression—results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine. More importantly we demonstrated that 1-methyl-D-tryptophan was able to alleviate most of the behavioural changes resulting from UCMS exposure. We also showed that both fluoxetine and 1-methyl-D-tryptophan robustly reduced peripheral levels of proinflammatory cytokines in UCMS mice suggesting that their therapeutic effects might occur through anti-inflammatory processes. KP inhibition might be involved in the positive effects of fluoxetine on mice behaviour and could be a relevant strategy to counteract depressive-like symptoms. PMID:27828964

  10. Acute scurvy during treatment with interleukin-2.

    PubMed

    Alexandrescu, D T; Dasanu, C A; Kauffman, C L

    2009-10-01

    The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms.

  11. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine

    PubMed Central

    Kaur, Ginpreet; Invally, Mihir; Sanzagiri, Resham; Buttar, Harpal S.

    2015-01-01

    Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and Methods: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Results: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of

  12. Fluoxetine enhanced neurogenesis is not translated to functional outcome in stroke rats.

    PubMed

    Sun, Xiaoyu; Sun, Xuan; Liu, Tingting; Zhao, Mei; Zhao, Shanshan; Xiao, Ting; Jolkkonen, Jukka; Zhao, Chuansheng

    2015-08-31

    Fluoxetine is widely used in clinical practice. It regulates hippocampal neurogenesis, however, the effect of fluoxetine on neurogenesis in the subventricular zone (SVZ) remains controversial. We aimed to study the effect of fluoxetine on neurogenesis in the SVZ and subgranular zone (SGZ) of dentate gyrus (DG) in relation to behavioral recovery after stroke in rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Fluoxetine was orally administrated starting 1 week after ischemia, with a dose of 16mg/kg/day for 3 weeks. Focal cerebral ischemia was induced by intracranial injection of vasoconstrictive peptide endothelin-1(ET-1). Behavioral recovery was evaluated on post-stroke days 29-31 after which the survival rate and fate of proliferating cells in the SVZ and DG were measured by immunohistochemistry. The production of neuroblasts in both the SVZ and DG was significantly increased after stroke. Chronic post-stroke fluoxetine treatment increased the dendritic complexity of newborn dentate granule cells. However, fluoxetine treatment did not influence the survival or differentiation of newly generated cells. Neither fluoxetine treatment improved sensorimotor recovery following focal cerebral ischemia.

  13. Treatment of acute lower limb ischaemia.

    PubMed

    Lukasiewicz, Aleksander

    2016-01-01

    Acute lower limb ischaemia poses a major threat to limb survival. For many years surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution in the management of acute lower limb ischaemia. A wide range of endovascular procedures can nowadays be employed, providing results at least as good as the traditional surgical approach. This paper is an overview of currently utilised endovascular options as well as recent modifications of standard surgical techniques.

  14. A comparison of fluoxetine, imipramine, and placebo in patients with major depressive disorder.

    PubMed

    Cohn, J B; Wilcox, C

    1985-03-01

    The efficacy and safety of fluoxetine were compared with those of imipramine and of placebo in a 6-week randomized double-blind parallel study of patients with major depressive illness. Mean values for all efficacy measurements were improved over baseline with fluoxetine and imipramine treatment (p less than .001). More fluoxetine patients completed the study than did imipramine or placebo patients. Predominant adverse experiences reported by imipramine patients were dry mouth and dizziness/lightheadedness. Predominant adverse experiences reported by fluoxetine patients were drowsiness/sedation and excessive sweating. In a subsequent 48-week open-label study, the predominant adverse experience in the fluoxetine group was excessive sweating and in the imipramine group was still dry mouth. In this study, fluoxetine relieved the symptoms of major depressive illness effectively and significantly better than placebo and was better tolerated than imipramine.

  15. Subchronical treatment with Fluoxetine modifies the activity of the MCHergic and hypocretinergic systems. Evidences from peptide CSF concentration and gene expression.

    PubMed

    Calegare, Bruno F; Costa, Alicia; Fernandes, Leandro; Dias, Ana L; Torterolo, Pablo; Almeida, Vânia D'

    2016-01-01

    In the postero-lateral hypothalamus are located two neuronal systems that utilize the neuropeptides melanin-concentrating hormone (MCH) and hypocretins (also called orexins) as neuromodulators. These systems have reciprocal connections between them, and project throughout the central nervous system. MCH has been involved in the generation of sleep, mainly REM sleep, while hypocretins have a critical role in the generation of wakefulness. MCHergic activity is also involved in the pathophysiology of major depressive disorder (MD). In this regards, intracerebral administration of MCH promotes pro-depressive behaviors (i.e., immobility in the forced swimming test) and REM sleep hypersomnia, which is an important trait of depression. Furthermore, the antagonism of the MCHR-1 receptor has a reliable antidepressant effect, suggesting that MCH is a pro-depressive factor. Hypocretins have been also involved in mood regulation; however, their role in depression is still on debate. Taking these data into account, we explored whether systemic subchronical treatment with Fluoxetine (FLX), a serotonergic antidepressant, modifies the concentration of MCH in the cerebrospinal fluid (CSF), as well as the preproMCH mRNA expression. We also evaluated the hypocretinergic system by quantifying the hypocretin-levels in the CSF and the preprohypocretin mRNA expression. Compared to control, FLX increased the levels of preprohypocretin mRNA without affecting the hypocretin-1 CSF levels. On the contrary, FLX significantly decreased the MCH CSF concentration without affecting the preproMCH gene expression. This result is in agreement with the fact that MCH serum level diminishes during the antidepressant treatment in MD, and supports the hypothesis that an increase in the MCHergic activity could have pro-depressive consequences.

  16. Fluoxetine versus other types of pharmacotherapy for depression

    PubMed Central

    Cipriani, Andrea; Brambilla, Paulo; Furukawa, Toshi A; Geddes, John; Gregis, Manuela; Hotopf, Matthew; Malvini, Lara; Barbui, Corrado

    2014-01-01

    Background Depression is common in primary care and it is associated with marked personal, social and economic morbidity, and creates significant demands on service providers in terms of workload. Treatment is predominantly pharmaceutical or psychological. Fluoxetine, the first of a group of antidepressant (AD) agents known as selective serotonin reuptake inhibitors (SSRIs), has been studied in many randomised controlled trials (RCTs) in comparison with tricyclic (TCA), heterocyclic and related ADs, and other SSRIs. These comparative studies provided contrasting findings. In addition, systematic reviews of RCTs have always considered the SSRIs as a group, and evidence applicable to this group of drugs might not be applicable to fluoxetine alone. The present systematic review assessed the efficacy and tolerability profile of fluoxetine in comparison with TCAs, SSRIs and newer agents. Objectives To determine the efficacy of fluoxetine, compared with other ADs, in alleviating the acute symptoms of depression, and to review its acceptability. Search methods Relevant studies were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (1966-2004) and Embase (1974-2004). Non-English language articles were included. Selection criteria Only RCTs were included. For trials which have a crossover design only results from the first randomisation period were considered. Data were independently extracted by two reviewers using a standard form. Responders to treatment were calculated on an intention-to-treat basis: drop-outs were always included in this analysis. When data on drop-outs were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were

  17. Adjunctive treatment of brexpiprazole with fluoxetine shows a rapid antidepressant effect in social defeat stress model: Role of BDNF-TrkB signaling

    PubMed Central

    Ma, Min; Ren, Qian; Yang, Chun; Zhang, Ji-chun; Yao, Wei; Dong, Chao; Ohgi, Yuta; Futamura, Takashi; Hashimoto, Kenji

    2016-01-01

    Addition of low doses of the atypical antipsychotic drug brexpiprazole with selective serotonin reuptake inhibitors (SSRIs) could promote antidepressant effect in patients with major depressive disorder although the precise mechanisms underlying the action of the combination are unknown. Combination of low dose of brexpiprazole (0.1 mg/kg) and SSRI fluoxetine (10 mg/kg) could promote a rapid antidepressant effect in social defeat stress model although brexpiprazole or fluoxetine alone did not show antidepressant effect. Furthermore, the combination significantly improved alterations in the brain-derived neurotrophic factor (BDNF) - TrkB signaling and dendritic spine density in the prefrontal cortex, hippocampus, and nucleus accumbens in the susceptible mice after social defeat stress. Interestingly, TrkB antagonist ANA-12 significantly blocked beneficial effects of combination of brexpiprazole and fluoxetine on depression-like phenotype. These results suggest that BDNF-TrkB signaling plays a role in the rapid antidepressant action of the combination of brexpiprazole and fluoxetine. PMID:27991542

  18. Decreased aggressive and locomotor behaviors in Betta splendens after exposure to fluoxetine.

    PubMed

    Kohlert, Jess G; Mangan, Brian P; Kodra, Christine; Drako, Linsay; Long, Emily; Simpson, Holly

    2012-02-01

    The failure of sewage treatment plants to remove pharmaceuticals such as fluoxetine from waste water has become a concern given that these products are being detected in the surface waters of many countries of the world. The effects of fluoxetine in sub-lethal doses on the neural systems and behaviors of aquatic life are worthy of investigation. This study investigated the effects of sub-lethal amounts fluoxetine dissolved in water on the aggressive and locomotor behaviors of 44 male Betta splendens. Fish treated with 705 microg/l of fluoxetine and 350 microg/l of fluoxetine generally demonstrated significant decreases in locomotion and number of aggressive attacks compared to 0 microg/l of fluoxetine (controls) on Days 11 and 19 of drug exposure and persisted for at least 13 days after removal of fluoxetine. Consistent with decreases in the number of aggressive attacks, there was a significant increase in aggression-response time to a perceived intruder for treated males on Days 11 and 19 and persisted for 6 days following removal of fluoxetine. However, the differences in aggressive and locomotor behaviors seen in the fluoxetine-treated groups were indistinguishable from controls three weeks following drug removal.

  19. Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

    PubMed

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; Lepera, José Salvador

    2013-03-01

    Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%).

  20. Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

    2007-01-01

    The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

  1. Fluoxetine, desipramine, and the dual antidepressant milnacipran reduce alcohol self-administration and/or relapse in dependent rats.

    PubMed

    Simon O'Brien, Emmanuelle; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël

    2011-06-01

    A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.

  2. A treatment for the acute migraine attack.

    PubMed

    Adam, E I

    1987-01-01

    A compound analgesic/anti-emetic formulation was significantly effective in reducing the severity of acute attacks of migraine, in a double-blind, randomized, crossover trial of 34 patients referred to a migraine clinic. The preparation contained paracetamol (acetaminophen) 500 mg, codeine phosphate 8 mg, buclizine hydrochloride 6.25 mg and dioctyl sodium sulphosuccinate 10 mg. The dosage was two tablets taken as early as possible in the acute attack. No specific factors could be identified which influenced response to treatment. Patients with a long history of migraine (more than 10 years) responded as well as those with a recent onset of the condition.

  3. Treatment of acute and remote symptomatic seizures.

    PubMed

    Koppel, Barbara S

    2009-07-01

    In principle, the use of anticonvulsant drugs does not differ between acute and remote symptomatic seizures, but control of acute symptomatic seizures requires simultaneous treatment of the underlying etiology. Prevention of remote seizures when the risk is known to be high has been the subject of intense efforts at antiepileptogenesis, but the optimal duration of treatment after an injury is not yet known. Appropriate evaluation of a seizure depends on individual circumstances, but findings on examination, laboratory tests (serum electrolytes, magnesium, glucose, assessment of hepatic and renal function), and brain imaging (CT scan or MRI) are necessary to determine the most likely cause. Lumbar puncture is always required when there is suspicion of meningitis or encephalitis. Preferred medications for treatment of acute symptomatic seizures or status epilepticus are those available for intravenous use, such as benzodiazepines, fosphenytoin or phenytoin, valproate, levetiracetam, and phenobarbital. Diazepam is also available as a gel for rectal administration. Seizures that occur in patients with epilepsy because of missed antiepileptic drugs or inadequate serum levels should be treated with additional doses of their regular medications; loading doses can be administered with minimal toxicity in tolerant patients. Surgery is rarely necessary in the acute setting except for intracerebral lesions with rapidly rising intracranial pressure and impending herniation. After seizures are controlled, the provoking condition must also be determined and treated.

  4. Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats.

    PubMed

    McNamara, Robert K; Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W

    2013-12-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here, we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group was administered FLX (10mg/kg/day) for 30days (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-25%, p≤0.0001) and DEF+FLX (-28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  5. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Leukemia (AML) About Acute Myeloid Leukemia (AML) What’s New in Acute Myeloid Leukemia Research and Treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  6. Treatment of Children with APL (Acute Promyelocytic Leukemia)

    MedlinePlus

    ... Childhood Leukemia Treatment of Children With Acute Promyelocytic Leukemia (APL) Treatment of acute promyelocytic leukemia (APL), the ... With Chronic Myelogenous Leukemia (CML) More In Childhood Leukemia About Childhood Leukemia Causes, Risk Factors, and Prevention ...

  7. Microbiology and treatment of acute apical abscesses.

    PubMed

    Siqueira, José F; Rôças, Isabela N

    2013-04-01

    Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease.

  8. Microbiology and Treatment of Acute Apical Abscesses

    PubMed Central

    Rôças, Isabela N.

    2013-01-01

    SUMMARY Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

  9. Fluoxetine and sertraline attenuate postischemic brain injury in mice.

    PubMed

    Shin, Tae Kyeong; Kang, Mi Sun; Lee, Ho Youn; Seo, Moo Sang; Kim, Si Geun; Kim, Chi Dae; Lee, Won Suk

    2009-06-01

    This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1alpha proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

  10. Pycnogenol treatment of acute hemorrhoidal episodes.

    PubMed

    Belcaro, Gianni; Cesarone, Maria Rosaria; Errichi, Bruno; Di Renzo, Andrea; Grossi, Maria Giovanna; Ricci, Andrea; Dugall, Mark; Cornelli, Umberto; Cacchio, Marisa; Rohdewald, Peter

    2010-03-01

    We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings.

  11. Acute hepatitis C: prevention and treatment.

    PubMed

    Ozaras, Resat; Tahan, Veysel

    2009-04-01

    HCV can cause acute or chronic hepatitis and is a health problem all over the world. It is one of the leading causes of cirrhosis and hepatocellular carcinoma, and is a common indication for liver transplantation. Unrecognized patients with HCV infection may transmit the virus to uninfected people. The acute form of the disease leads to chronic hepatitis in the majority of cases. Since the success rate of treatment given in the chronic phase is much lower than that given in the acute phase, recognizing acute hepatitis is critical. Although HCV is less prevalent since 1990s in the Western world after improved blood-donor screening programs, needle-exchange facilities and education among intravenous drug users, it is still endemic in some regions, including African countries, Egypt, Taiwan, China and Japan. Acute HCV infection may be a challenge for the clinician; since it is often asymptomatic, detection and diagnosis are usually difficult. After an incubation period of 7 weeks (2-12 weeks), only a minority of patients (10-15%) report symptoms. The spontaneous clearance of the virus is more frequent primarily during the first 3 months of clinical onset of the disease, but may occur anytime during the 6 months of acute infection. This spontaneous resolution seems to be more frequent in symptomatic cases. Viremia persisting more than 6 months is accepted as chronic infection. The virus is transmitted more frequently through infected blood or body fluids. Detection of antibodies against HCV is not a reliable method of diagnosing acute HCV infection since the appearance of antibodies against HCV can be delayed in up to 30% of patients at the onset of symptoms. Thus, the diagnosis of acute hepatitis C relies on the qualitative detection of HCV RNA, which may appear as early as 1-2 weeks after exposure quickly followed by highly elevated alanine aminotransferase. After a follow-up period of 8-12 weeks for allowing spontaneous resolution, treatment should be initiated

  12. Elevation of brain allopregnanolone rather than 5-HT release by short term, low dose fluoxetine treatment prevents the estrous cycle-linked increase in stress sensitivity in female rats.

    PubMed

    Devall, Adam J; Santos, Julia M; Fry, Jonathan P; Honour, John W; Brandão, Marcus L; Lovick, Thelma A

    2015-01-01

    Withdrawal from long-term dosing with exogenous progesterone precipitates increased anxiety-linked changes in behavior in animal models due to the abrupt decrease in brain concentration of allopregnanolone (ALLO), a neuroactive metabolite of progesterone. We show that a withdrawal-like effect also occurs during the late diestrus phase (LD) of the natural ovarian cycle in rats, when plasma progesterone and ALLO are declining but estrogen secretion maintains a stable low level. This effect at LD was prevented by short-term treatment with low dose fluoxetine. During LD, but not at other stages of the estrous cycle, exposure to anxiogenic stress induced by whole body vibration at 4 Hz for 5 min evoked a significant decrease in tail flick latency (stress-induced hyperalgesia) and a decrease in the number of Fos-positive neurons present in the periaqueductal gray (PAG). The threshold to evoke fear-like behaviors in response to electrical stimulation of the dorsal PAG was lower in the LD phase, indicating an increase in the intrinsic excitability of the PAG circuitry. All these effects were blocked by short-term administration of fluoxetine (2 × 1.75 mg kg(-1) i.p.) during LD. This dosage increased the whole brain concentration of ALLO, as determined using gas chromatography-mass spectrometry, but was without effect on the extracellular concentration of 5-HT in the dorsal PAG, as measured by microdialysis. We suggest that fluoxetine-induced rise in brain ALLO concentration during LD offsets the sharp physiological decline, thus removing the trigger for the development of anxiogenic withdrawal effects.

  13. 21 CFR 520.980 - Fluoxetine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Fluoxetine. 520.980 Section 520.980 Food and Drugs..., AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.980 Fluoxetine. (a) Specifications. Each chewable tablet contains 8, 16, 32, or 64 milligrams (mg) fluoxetine hydrochloride. (b) Sponsor. See...

  14. 21 CFR 520.980 - Fluoxetine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Fluoxetine. 520.980 Section 520.980 Food and Drugs..., AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.980 Fluoxetine. (a) Specifications. Each chewable tablet contains 8, 16, 32, or 64 milligrams (mg) fluoxetine hydrochloride. (b) Sponsor. See...

  15. 21 CFR 520.980 - Fluoxetine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fluoxetine. 520.980 Section 520.980 Food and Drugs..., AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.980 Fluoxetine. (a) Specifications. Each chewable tablet contains 8, 16, 32, or 64 milligrams (mg) fluoxetine hydrochloride. (b) Sponsor. See...

  16. Fluoxetine may influence lordosis of rats through effects on midbrain 3 alpha,5 alpha-THP concentrations.

    PubMed

    Frye, Cheryl A; Petralia, Sandra M; Rhodes, Madeline E; Stein, Benjamin

    2003-12-01

    5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) in the ventral tegmental area (VTA) mediates lordosis of rodents. If fluoxetine's effects on lordosis are mediated in part by midbrain 3alpha,5alpha-THP, then fluoxetine regimens that decrease and increase lordosis would be expected to respectively lower and elevate midbrain 3alpha,5-THP levels. Experiment 1: Ovariectomized (ovx) rats received estradiol benzoate (EB; 5 micro g, SC) at 0 and 24 h and fluoxetine (20 mg/kg, IP) or vehicle 30 min before sex testing and tissue collection. Other rats received fluoxetine (10 mg/kg, IP) or vehicle for 15 days followed by EB-priming and testing. Systemic acute or chronic fluoxetine significantly decreased lordosis and midbrain 3alpha,5alpha-THP levels compared to vehicle. Experiment 2: Ovx rats with unilateral cannula to the VTA were primed with EB (5 micro g; 0, 24 h) and/or progesterone (0 or 100 micro g; 44 h, SC). At 47.5 h, fluoxetine (3.6 mM) or vehicle was infused to the VTA. At 48 h, rats were tested. Administering fluoxetine to the VTA significantly increased lordosis and midbrain 3alpha,5alpha-THP levels compared to vehicle infusions. Experiment 3: Ovx EB-primed rats were tested prior to, and 30 min after, treatmemt with acute fluoxetine (20 mg/kg, IP). Rats were then infused with 3alpha,5alpha-THP (100 ng) or vehicle to the VTA and were retested. 3alpha,5alpha-THP, but not vehicle, to the VTA reversed acute fluoxetine's inhibitory effects on lordosis. Together, these data suggest fluoxetine may alter lordosis in part through actions of 3alpha-THP in the midbrain.

  17. Acute Time to Response in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Kratochvil, Christopher; Emslie, Graham; Silva, Susan; McNulty, Steve; Walkup, John; Curry, John; Reinecke, Mark; Vitiello, Benedetto; Rohde, Paul; Feeny, Nora; Casat, Charles; Pathak, Sanjeev; Weller, Elizabeth; May, Diane; Mayes, Taryn; Robins, Michele; March, John

    2006-01-01

    Objective: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). Method: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo…

  18. Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

    PubMed

    Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

    2014-10-01

    We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014.

  19. Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation.

    PubMed

    Monteiro Filho, Waldo Oliveira; de Torres, Sandra Maria; Amorim, Marleyne José Afonso Accioly Lins; Andrade, Anderson Joel Martino; de Morais, Rosana Nogueira; Tenorio, Bruno Mendes; da Silva Junior, Valdemiro Amaro

    2014-10-01

    Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

  20. Treatment of acute cyanide intoxication with hemodialysis.

    PubMed

    Wesson, D E; Foley, R; Sabatini, S; Wharton, J; Kapusnik, J; Kurtzman, N A

    1985-01-01

    A dramatic response was noted in a patient at our hospital who received hemodialysis therapy for severe acidosis secondary to an unknown toxin, subsequently identified as cyanide. We were unable to find any information concerning the hemodialysis clearance and extraction ratio of cyanide; thus, we studied the effect of hemodialysis in dogs receiving a constant infusion of cyanide with and without a simultaneous infusion of thiosulfate. The hemodialysis clearance of cyanide in the presence of thiosulfate was 38.3 +/- 5.4 ml/min with an extraction ratio of 0.43 +/- 0.06 (n = 4). Hemodialysis was found to increase the lethal dose of cyanide without thiosulfate infusion, and a further increase was noted with the thiosulfate infusion. Thiosulfate promotes mitochondrial metabolism of cyanide to thiocyanate. The end product, thiocyanate, is quickly removed by hemodialysis. We believe that the demonstrated effectiveness of hemodialysis in the treatment of acute cyanide intoxication is related not only to the hemodialysis clearance of cyanide, but also to the removal of its metabolic end product, thiocyanate. Based on our observations, we feel that hemodialysis is an effective adjunct in the treatment of acute cyanide intoxication.

  1. [Surgical and therapeutic treatment of acute pancreatitis].

    PubMed

    Sandakov, P Ia; Samartsev, V A; Mineev, D A

    2014-01-01

    It was analyzed the features of different forms of acute pancreatitis in 1001 patients including 324 cases with pancreatonecrosis and 245 patients with middle severity of disease. It was shown that monitoring of patients' condition and destructive process in pancreas by using of modified SOFA-scale and evaluation of sonographic signs of inflammation are advisable. Flow indicators including resistance index and the maximum flow velocity in celiac trunk and superior mesenteric artery represented severity of gland's destruction. Sonographic investigation revealed small-focal pancreonecrosis. It allows to differentiate medical tactics. Surgical treatment was performed in 582 patients. Efficiency of surgical treatment is determined by diagnostic methods, timely sanation of destructive focuses of pancreas, abdominal cavity, retroperitoneal fiber, adequate drainage and mini-invasive techniques using in case of purulent complications. The main prognostic factors of development of complications and adverse outcomes are determined.

  2. [Treatment guidelines for acute and preventive treatment of cluster headache].

    PubMed

    Chen, Ping-Kun; Chen, Hsi-Ming; Chen, Wei-Hung; Chen, Yeng-Yu; Fuh, Jong-Ling; Lee, Lian-Hui; Liao, Yi-Chu; Lin, Kao-Chang; Tseng, Hung-Ping; Tsai, Jing-Jane; Wang, Po-Jen; Wang, Shuu-Jiun; Yang, Chun-Pai; Yiu, Chun-Hing; Wu, Zin-An

    2011-09-01

    The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated both the acute and the preventive treatments for cluster headache now being used in Taiwan, based on the principles of evidence- based medicine. We assessed the quality of clinical trials and levels of evidence, and referred to other treatment guidelines proposed by other countries. Throughout several panel discussions, we merged opinions from the subcommittee members and proposed a consensus on the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice regarding acute and preventive treatments of cluster headache. The majority of Taiwanese patients have episodic cluster headaches, because chronic clusters are very rare. Cluster headache is characterized by severe and excruciating pain which develops within a short time and is associated with ipsilateral autonomic symptoms. Therefore, emergency treatment for a cluster headache attack is extremely important. Within the group of acute medications currently available in Taiwan, the subcommittee determined that high-flow oxygen inhalation has the best evidence of effectiveness, followed by intranasal triptans. Both are recommended as first-line medical treatments for acute attacks. Oral triptans were determined to be second-line medications. For transitional prophylaxis, oral corticosteroids are recommended as the first-line medication, and ergotamine as the second-line choice. As for maintenance prophylaxis, verapamil has the best evidence and is recommended as the first-line medication. Lithium, melatonin, valproic acid, topiramate and gabapentin are suggested as the second-line preventive medications. Surgical interventions, including occipital nerve stimulation, deep brain stimulation, radiofrequency block of the sphenopalatine ganglion, percutaneous radiofrequency rhizotomy and trigeminal nerve section, are invasive and their long-term efficacy and adverse events are still not clear in

  3. Increasing spinal 5-HT2A receptor responsiveness mediates anti-allodynic effect and potentiates fluoxetine efficacy in neuropathic rats. Evidence for GABA release.

    PubMed

    Dupuis, Amandine; Wattiez, Anne-Sophie; Pinguet, Jérémy; Richard, Damien; Libert, Frédéric; Chalus, Maryse; Aissouni, Youssef; Sion, Benoit; Ardid, Denis; Marin, Philippe; Eschalier, Alain; Courteix, Christine

    2017-04-01

    Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia. Tactile allodynia was assessed in spinal nerve ligation-induced neuropathic pain in rats using von Frey filaments after acute treatment with TAT-2ASCV and/or 5-HT2A receptor agonist, alone or in combination with repeated treatment with fluoxetine. In vivo microdialysis was performed in order to examine the involvement of GABA in TAT-2ASCV/fluoxetine treatment-associated analgesia. TAT-2ASCV (100ng, single i.t. injection) improved SNL-induced tactile allodynia by increasing 5-HT2A receptor responsiveness to endogenous 5-HT. Fluoxetine alone (10mg/kg, five i.p. injections) slightly increased tactile thresholds and its co-administration with TAT-2ASCV (100ng, single i.t. injection) further enhanced the anti-allodynic effect. This effect depends on the integrity of descending serotonergic bulbospinal pathways and spinal release of GABA. The anti-allodynic effect of fluoxetine can be enhanced by disrupting 5-HT2A receptor-PDZ protein interactions. This enhancement depends on 5-HT2A receptor activation, spinal GABA release and GABAA receptor activation.

  4. Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors.

    PubMed

    Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol

    2013-08-01

    Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats.

  5. Treatment and pathogenesis of acute hyperkalemia

    PubMed Central

    Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

    2012-01-01

    This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

  6. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

    PubMed

    Kroeze, Y; Peeters, D; Boulle, F; Pawluski, J L; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-09-22

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders.

  7. An evaluation of behavioural endpoints: The pharmaceutical pollutant fluoxetine decreases aggression across multiple contexts in round goby (Neogobius melanostomus).

    PubMed

    McCallum, Erin S; Bose, Aneesh P H; Warriner, Theresa R; Balshine, Sigal

    2017-05-01

    Fluoxetine (Prozac™) is designed to alter human behaviour; however, because many physiological pathways are conserved across vertebrates, this drug may affect the behaviour of fish living in fluoxetine-polluted environments. Although a number of studies have used behaviour to document the sub-lethal effects of fluoxetine, the repeatability of these effects across experiments, across behavioural contexts, and over different exposure durations are rarely considered. Here, we conducted two experiments and assessed how fluoxetine exposure affected a range of fitness-related behaviours in wild round goby (Neogobius melanostomus). We found that fluoxetine impacts round goby behaviour at high (40 μg/l) doses, but not at environmentally relevant low doses (1 μg/l). In both experiments, an acute 3-day exposure to fluoxetine reduced round goby aggression in multiple behavioural contexts, but had no detectable effect on overall activity or social affiliative behaviour. While a chronic 28-day exposure to fluoxetine exposure still reduced aggression, this reduction was only detectable in one behavioural context. Our findings demonstrate the importance of repeated behavioural testing (both between and within experiments) and contribute to a growing body of literature evaluating the effects of fluoxetine and other pharmaceuticals on animal behaviour.

  8. Polysomnographic sleep effects of fluoxetine and nefazodone on a seasonal affective disorder patient.

    PubMed

    Shen, Jianhua; Shapiro, Colin

    2002-11-01

    This reported person met DSM-III-R criteria for seasonal affective disorder. In successive years she had two treatments with fluoxetine and one with nefazodone. Every year regular polysomnographic monitoring was carried out during the critical initial 8 weeks of treatment. The results indicate that on both occasions fluoxetine decreased the patient's sleep quality. Nefazodone had no sleep disturbing effects and on withdrawal no relapse has been seen for 3 years.

  9. Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.

    PubMed

    Van Waes, Vincent; Vandrevala, Malcolm; Beverley, Joel; Steiner, Heinz

    2014-11-01

    There is a growing use of psychostimulants, such as methylphenidate (Ritalin; dopamine re-uptake inhibitor), for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin re-uptake inhibitors (SSRIs), including fluoxetine, can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine, in conjunction with methylphenidate, in adolescent rats facilitated a gene regulation effect well established for repeated exposure to illicit psychostimulants such as cocaine-blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs, such as fluoxetine, may increase the addiction liability of methylphenidate.

  10. A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients.

    PubMed

    Diaz-Martinez, A; Benassinni, O; Ontiveros, A; Gonzalez, S; Salin, R; Basquedano, G; Martinez, R A

    1998-01-01

    In this randomized, open-label, 8-week comparative study, the efficacy and safety of venlafaxine and fluoxetine were assessed in outpatients with major depression. One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to improve patient response, the dosage could be increased at the investigator's discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One hundred forty-five patients were evaluated for safety and 110, for efficacy. The mean age was 37 years, and 70% of the patients were female. In both treatment groups, mean scores on the Hamilton Depression Rating Scale decreased significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the Montgomery-Asberg Depression Rating Scale decreased significantly between baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3, venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%), and generalized tremor (20.0%). The results of this study indicate that venlafaxine is effective and well tolerated for the treatment of major depression at doses of 37.5 or 75 mg twice daily and not significantly different from fluoxetine 20 or 40 mg once daily.

  11. Acute migraine: Current treatment and emerging therapies

    PubMed Central

    Kalra, Arun A; Elliott, Debra

    2007-01-01

    Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal “cure” eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure. PMID:18488069

  12. Acute Iliac Artery Rupture: Endovascular Treatment

    SciTech Connect

    Chatziioannou, A.; Mourikis, D.; Katsimilis, J.; Skiadas, V. Koutoulidis, V.; Katsenis, K.; Vlahos, L.

    2007-04-15

    The authors present 7 patients who suffered iliac artery rupture over a 2 year period. In 5 patients, the rupture was iatrogenic: 4 cases were secondary to balloon angioplasty for iliac artery stenosis and 1 occurred during coronary angioplasty. In the last 2 patients, the rupture was secondary to iliac artery mycotic aneurysm. Direct placement of a stent-graft was performed in all cases, which was dilated until extravasation was controlled. Placement of the stent-graft was successful in all the cases, without any complications. The techniques used, results, and mid-term follow-up are presented. In conclusion, endovascular placement of a stent-graft is a quick, minimally invasive, efficient, and safe method for emergency treatment of acute iliac artery rupture, with satisfactory short- and mid-term results.

  13. Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study

    PubMed Central

    Yılmaz, Ahmet; Elbey, Bilal; Yazgan, Ümit Can; Dönder, Ahmet; Arslan, Necmi; Arslan, Serkan; Alabalık, Ulaş; Aslanhan, Hamza

    2016-01-01

    Background. The aim of the study was to analyse the effect of caffeic acid phenethyl ester (CAPE) on fluoxetine-induced hepatotoxicity in rats. Materials and Methods. Group I served as control. Group II received CAPE intraperitoneally. Group III received fluoxetine per orally. Group IV received fluoxetine and CAPE. The total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and liver enzymes including paraoxonase-1 (PON-1), aspartate transaminase, and alanine transaminase levels were measured. Liver tissues were processed histopathologically for evaluation of liver injury and to validate the serum enzyme levels. Results. An increase in TOS and OSI and a decrease in TAC and PON-1 levels in serum and liver tissues of Group III were observed compared to Groups I and II. After treatment with CAPE, the level of TOS and OSI decreased while TAC and PON-1 increased in serum and liver in Group IV. Histopathological examination of the liver revealed hepatic injury after fluoxetine treatment and reduction of injury with CAPE treatment. Conclusion. Our results suggested that CAPE treatment provided protection against fluoxetine toxicity. Following CAPE treatment with fluoxetine-induced hepatotoxicity, TOS and OSI levels decreased, whereas PON-1 and TAC increased in the serum and liver. PMID:27144157

  14. Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study.

    PubMed

    Yılmaz, Ahmet; Elbey, Bilal; Yazgan, Ümit Can; Dönder, Ahmet; Arslan, Necmi; Arslan, Serkan; Alabalık, Ulaş; Aslanhan, Hamza

    2016-01-01

    Background. The aim of the study was to analyse the effect of caffeic acid phenethyl ester (CAPE) on fluoxetine-induced hepatotoxicity in rats. Materials and Methods. Group I served as control. Group II received CAPE intraperitoneally. Group III received fluoxetine per orally. Group IV received fluoxetine and CAPE. The total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and liver enzymes including paraoxonase-1 (PON-1), aspartate transaminase, and alanine transaminase levels were measured. Liver tissues were processed histopathologically for evaluation of liver injury and to validate the serum enzyme levels. Results. An increase in TOS and OSI and a decrease in TAC and PON-1 levels in serum and liver tissues of Group III were observed compared to Groups I and II. After treatment with CAPE, the level of TOS and OSI decreased while TAC and PON-1 increased in serum and liver in Group IV. Histopathological examination of the liver revealed hepatic injury after fluoxetine treatment and reduction of injury with CAPE treatment. Conclusion. Our results suggested that CAPE treatment provided protection against fluoxetine toxicity. Following CAPE treatment with fluoxetine-induced hepatotoxicity, TOS and OSI levels decreased, whereas PON-1 and TAC increased in the serum and liver.

  15. Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors.

    PubMed

    Haj-Mirzaian, Arya; Kordjazy, Nastaran; Ostadhadi, Sattar; Amiri, Shayan; Haj-Mirzaian, Arvin; Dehpour, AhmadReza

    2016-06-01

    Opioid and N-methyl-d-aspartate (NMDA) receptors mediate different effects of fluoxetine. We investigated whether opioid and NMDA receptors are involved in the protective effect of fluoxetine against the behavioral despair induced by acute physical stress in male mice. We used the forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) for behavioral evaluation. We used fluoxetine, naltrexone (opioid receptor antagonist), MK-801 (NMDA receptor antagonist), morphine (opioid receptor agonist), and NMDA (NMDA receptor agonist). Acute foot-shock stress (FSS) significantly induced behavioral despair (depressive-like) and anxiety-like behaviors in tests. Fluoxetine (5 mg/kg) reversed the depressant-like effect of FSS, but it did not alter the locomotion and anxiety-like behavior in animals. Acute administration of subeffective doses of naltrexone (0.3 mg/kg) or MK-801 (0.01 mg/kg) potentiated the antidepressant-like effect of fluoxetine, while subeffective doses of morphine (1 mg/kg) and NMDA (75 mg/kg) abolished this effect of fluoxetine. Also, co-administration of subeffective doses of naltrexone (0.05 mg/kg) and MK-801 (0.003 mg/kg) with fluoxetine (1 mg/kg) induced a significant decrease in the immobility time in FST and TST. Our results showed that opioid and NMDA receptors (alone or in combination) are involved in the antidepressant-like effect of fluoxetine against physical stress.

  16. Fluoxetine prevents oligodendrocyte cell death by inhibiting microglia activation after spinal cord injury.

    PubMed

    Lee, Jee Y; Kang, So R; Yune, Tae Y

    2015-05-01

    Oligodendrocyte cell death and axon demyelination after spinal cord injury (SCI) are known to be important secondary injuries contributing to permanent neurological disability. Thus, blocking oligodendrocyte cell death should be considered for therapeutic intervention after SCI. Here, we demonstrated that fluoxetine, an antidepressant drug, alleviates oligodendrocyte cell death by inhibiting microglia activation after SCI. After injury at the T9 level with a Precision Systems and Instrumentation (Lexington, KY) device, fluoxetine (10 mg/kg, intraperitoneal) was administered once a day for the indicated time points. Immunostaining with CD11b (OX-42) antibody and quantification analysis showed that microglia activation was significantly inhibited by fluoxetine at 5 days after injury. Fluoxetine also significantly inhibited activation of p38 mitogen-activated protein kinase (p38-MAPK) and expression of pro-nerve growth factor (pro-NGF), which is known to mediate oligodendrocyte cell death through the p75 neurotrophin receptor after SCI. In addition, fluoxetine attenuated activation of Ras homolog gene family member A and decreased the level of phosphorylated c-Jun and, ultimately, alleviated caspase-3 activation and significantly reduced cell death of oligodendrocytes at 5 days after SCI. Further, the decrease of myelin basic protein, myelin loss, and axon loss in white matter was also significantly blocked by fluoxetine, as compared to vehicle control. These results suggest that fluoxetine inhibits oligodendrocyte cell death by inhibiting microglia activation and p38-MAPK activation, followed by pro-NGF production after SCI, and provide a potential usage of fluoxetine for a therapeutic agent after acute SCI in humans.

  17. Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice.

    PubMed

    Jin, Li; Gao, Li-Feng; Sun, Dong-Sheng; Wu, Hao; Wang, Qun; Ke, Dan; Lei, Hao; Wang, Jian-Zhi; Liu, Gong-Ping

    2016-06-21

    Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer's disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3 × TgAD mice were treated with fluoxetine for 15 days, and then the influence of fluoxetine was detected at 20 days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3 × TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.

  18. The Treatment for Adolescents with Depression Study (TADS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    n/a; n/a

    2005-01-01

    Objective: The Treatment for Adolescents With Depression Study is a multicenter, randomized clinical trial sponsored by the NIMH. This study is designed to evaluate the short- and long-term effectiveness of four treatments for adolescents with major depressive disorder: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely,…

  19. Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways.

    PubMed

    Young, Kung-Chia; Bai, Chyi-Huey; Su, Hui-Chen; Tsai, Pei-Ju; Pu, Chien-Yu; Liao, Chao-Sheng; Lin, Yu-Min; Lai, Hsin-Wen; Chong, Lee-Won; Tsai, Yau-Sheng; Tsao, Chiung-Wen

    2014-10-01

    More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals.

  20. Pulmonary embolism: treatment of the acute episode.

    PubMed

    Casazza, Franco; Roncon, Loris; Greco, Francesco

    2005-10-01

    The prognosis of acute pulmonary embolism (PE) is mainly related to the clinical presentation and circulatory state of the patient: the therapeutic strategy is consequently different, ranging from an aggressive treatment in patients in life-threatening clinical conditions to a "stabilization" treatment in those hemodynamically stable. Since the majority of PE patients are clinically stable, a well conducted anticoagulant therapy, either with unfractionated or low-molecular-weight heparins together with a vitamin K antagonist, is sufficient to stop thrombus extension, to minimize the risk of recurrent embolism and prevent mortality. In about 15-20% of cases presenting with clinical instability of variable severity, prompt intravenous thrombolysis with a short-acting compound often represents a life-saving treatment and should be the first-line approach. In normotensive patients with right ventricular dysfunction at echocardiography, who represent about 30% of PE patients, the debate regarding the optimal therapy is still open and further studies are required to document a clinically relevant improvement in the benefit-risk ratio of thrombolytic agents over heparin alone: young people, with a very low risk of bleeding and a concomitant reduction of cardiopulmonary reserve might be the best candidates to systemic thrombolysis. In any case such patients should be admitted to an intensive care unit to monitor the clinical status for at least 48-72 hours and detect signs of possible hemodynamic worsening. Mechanical thrombectomy, either percutaneous or surgical, are ancillary procedures and should be reserved to a minority of highly compromised patients who are unable to receive thrombolysis.

  1. [Acute acalculous cholecystitis. Results of surgical treatment].

    PubMed

    de la Garza Villaseñor, L

    1993-01-01

    During an 11 year period, 47 patients with acute acalculous cholecystitis were operated on. Two to one male/female ratio was observed with a mean age of 55 age of 55 years. No one had a past history of biliary tract pathology but 70 per cent of the patients had risk factors, mainly diabetes mellitus, cardiovascular and collagenous diseases, some different of those reported in the world literature (sepsis, trauma, non biliary tract surgery, etc.). The ultrasound was the best diagnostic tool. Open cholecystectomy was performed in all patients and some sort of local complication was found in 85 per cent of patients (empyema, gangrene or perforation) in spite of the surgical procedure was done on emergency or early elective basis, a 31 per cent operative mortality rate was found and a 10.6% Operative mortality rates was observed. The bacterial cultures showed gram negative and anaerobic flora. This report shows that an early diagnosis and surgical treatment keeps a low morbidity and mortality rates but the gallbladder late complications have a high rates.

  2. Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background The perimenopausal period refers to the interval when women’s menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. Methods/design A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene’s Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. Discussion This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment

  3. [A comparative clinical evaluation of the antidepressive activity of fluoxetine and fluvoxamine].

    PubMed

    Lopukhov, I G

    1997-01-01

    Comparative study of the peculiarities of clinical action of fluoxetine and fluvoxamine in 65 patients with endogenous depressions revealed their high efficiency (in 74.3% and 64.3% respectively). Fluoxetine was characterised by predominance of a stimulating effect from the first days of treatment as well as by relatively late manifestation of very thymoleptic and tranquilizing impact (during 3-4 weeks). Fluvoxamin displayed relatively uniform occurrence of separate clinical effects together with predominance and early appearance of antidepressive influence. On the basis of the comparison of the peculiarities of either clinical action of fluoxetine and fluvoxamin or their side effects with those of traditional antidepressive drugs (amitryptilin and ludiomil) the preferable indications for their prescription were determined. Thus fluoxetine was very good in treatment of apathetic-adynamic depressions while fluvoxamin was recommended for therapy of anxious and melancholic depressions. Antidepressants studied were ranked in the following way in terms of decrease of sedative effect and increase of stimulating action: amitryptilin, fluvoxamin, ludiomil, fluoxetine. The proper thymoleptic effect of fluoxetine and fluvoxamin exceeded the same effect of amitryptilin and ludiomil.

  4. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present.

  5. Classification of observational data with artificial neural networks versus discriminant analysis in pharmacoepidemiological studies--can outcome of fluoxetine treatment be predicted?

    PubMed

    Winterer, G; Ziller, M; Linden, M

    1998-11-01

    For several years, there has been an ongoing discussion about appropriate methodological tools to be applied to observational data in pharmacoepidemiological studies. It is now suggested by our research group that artificial neural networks (ANN) might be advantageous in some cases for classification purposes when compared with discriminant analysis. This is due to their inherent capability to detect complex linear and nonlinear functions in multivariate data sets, the possibility of including data on different scales in the same model, as well as their relative resistance to "noisy" input. In this paper, a short introduction is given to the basics of neural networks and possible applications. For demonstration, a comparison between artificial neural networks and discriminant analysis was performed on a multivariate data set, consisting of observational data of 19738 patients treated with fluoxetine. It was tested, which of the two statistical tools outperforms the two other in regard to the therapeutic response prediction from the clinical input data. Essentially, it was found that neither discriminant analysis nor ANN are able to predict the clinical outcome on the basis of the employed clinical variables. Applying ANN, we were able to rule out the possibility of undetected suppressor effects to a greater extent than would have been possible by the exclusive application of discriminant analysis.

  6. [Some aspects of the complex treatment of acute suppurative perionitis].

    PubMed

    Kovalev, M M; Roĭ, V P; Zaritskiĭ, I; Konovalenko, V V; Mellin, V M

    1976-10-01

    The authors present an analysis of the results of complex treatment in 4318 patients operated upon for acute peritonitis, caused by acute appendicitis, perforating gastric and duodenal ulcers, acute cholecystitis, ruptures and perforations of the intestine and other surgical and gynecological diseases. Patients with diffuse purulent peritonitis showed marked disorders in protein-aminoacid, nitrogen, and water electrolyte metabolism, acid-base balance, a reduced nonspecific immune responsiveness of the organism. Therpeutic tactics was delineated taking into account the revealed changes.

  7. Fluoxetine: clinical pharmacology and physiologic disposition

    SciTech Connect

    Lemberger, L.; Bergstrom, R.F.; Wolen, R.L.; Farid, N.A.; Enas, G.G.; Aronoff, G.R.

    1985-03-01

    Fluoxetine (30 mg), administered for 7 days to normal volunteers, produced a 66% inhibition of tritiated serotonin uptake into platelets. Plasma concentrations of fluoxetine correlated positively with inhibition of serotonin uptake. Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality. Fluoxetine disappears from plasma with a half-life of 1-3 days; its metabolite norfluoxetine has a plasma half-life of 7-15 days. After administration of /sup 14/C-fluoxetine, approximately 65% of the administered dose of radioactivity is recovered in urine and about 15% in feces. Fluoxetine, given as a single dose or in multiple doses over 8 days, did not produce significant effects on the plasma disappearance of warfarin, diazepam, tolbutamide, or chlorothiazide. Coadministration of fluoxetine and ethanol did not result in an increase from control values in the blood ethanol levels, nor did it produce significant changes in physiologic, psychometric, or psychomotor activity. Pharmacokinetics of fluoxetine in the elderly and normal volunteers appear to be similar. In addition, pharmacokinetic analyses in patients with varying degrees of renal impairment did not show significant differences from healthy subjects.

  8. Assessment and treatment of patients with acute unstable bradycardia.

    PubMed

    Swift, Jennie

    Bradycardia is a slow heart rate that can lead to cardiac arrest or occur after initial resuscitation following cardiac arrest. This article provides information on acute unstable bradycardia and common arrhythmias. It focuses on the assessment of patients with acute bradycardia and how the presence or absence of adverse clinical features, in conjunction with an arrhythmia, dictates the necessity and choice of treatment.

  9. A single dose of vortioxetine, but not ketamine or fluoxetine, increases plasticity-related gene expression in the rat frontal cortex.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Sanchez, Connie; Wegener, Gregers; Elfving, Betina

    2016-09-05

    Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been shown to induce a rapid antidepressant effect in treatment-resistant patients. Vortioxetine is a multimodal-acting antidepressant that exert its therapeutic activity through serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibition and modulation of several 5-HT receptors. In clinical trials, vortioxetine improves depression symptoms and cognitive dysfunction. Neuroplasticity as well as serotonergic and glutamatergic signaling attain significant roles in depression pathophysiology and antidepressant responses. Here, we investigate the effects of ketamine and vortioxetine on gene expression related to serotonergic and glutamatergic neurotransmission as well as neuroplasticity and compare them to those of the selective serotonin reuptake inhibitor fluoxetine. Rats were injected with fluoxetine (10mg/kg), ketamine (15mg/kg), or vortioxetine (10mg/kg) at 2, 8, 12, or 27h prior to harvesting of the frontal cortex and hippocampus. mRNA levels were measured by real-time quantitative polymerase chain reaction (qPCR). The main finding was that vortioxetine enhanced plasticity-related gene expression (Mtor, Mglur1, Pkcα, Homer3, Spinophilin, and Synapsin3) in the frontal cortex at 8h after a single dose. Ingenuity pathway analysis of this subset of data identified a biological network that was engaged by vortioxetine and is plausibly associated with neuroplasticity. Transcript levels had returned to baseline levels 12h after injection. Only minor effects on gene expression were found for ketamine or fluoxetine. In conclusion, acute vortioxetine, but not fluoxetine or ketamine, transiently increased plasticity-related gene expression in the frontal cortex. These effects may be ascribed to the direct 5-HT receptor activities of vortioxetine.

  10. Peer social interaction is facilitated in juvenile rhesus monkeys treated with fluoxetine.

    PubMed

    Golub, Mari S; Hogrefe, Casey E; Bulleri, Alicia M

    2016-06-01

    Fluoxetine improves social interactions in children with autism, social anxiety and social phobia. It is not known whether this effect is mediated directly or indirectly by correcting the underlying pathology. Genetics may also influence the drug effect. Polymorphisms of the MAOA (monoamine oxidase A) gene interact with fluoxetine to influence metabolic profiles in juvenile monkeys. Juvenile nonhuman primates provide an appropriate model for studying fluoxetine effects and drug*gene interactions in children. Male rhesus monkeys 1-3 years of age living in permanent social pairs were treated daily with a therapeutic dose of fluoxetine or vehicle (n = 16/group). Both members of each social pair were assigned to the same treatment group. They were observed for social interactions with their familiar cagemate over a 2-year dosing period. Subjects were genotyped for MAOA variable number of tandem repeats (VNTR) polymorphisms categorized for high or low transcription rates (hi-MAOA, low-MAOA). Fluoxetine-treated animals spent 30% more time in social interaction than vehicle controls. Fluoxetine significantly increased the duration of quiet interactions, the most common type of interaction, and also of immature sexual behavior typical of rhesus in this age group. Specific behaviors affected depended on MAOA genotype of the animal and its social partner. When given fluoxetine, hi-MOAO monkeys had more social invitation and initiation behaviors and low-MAOA subjects with low-MAOA partners had more grooming and an increased frequency of some facial and vocal expressive behaviors. Fluoxetine may facilitate social interaction in children independent of remediation of psychopathology. Common genetic variants may modify this effect.

  11. Effect of fluoxetine on a neuronal, voltage-dependent potassium channel (Kv1.1)

    PubMed Central

    Tytgat, J; Maertens, Ch; Daenens, P

    1997-01-01

    Fluoxetine (Prozac) is widely used as an antidepressant drug and is assumed to be a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI). Claims that its beneficial psychotropic effects extend beyond those in treatment of depression have drawn clinical and popular attention to this compound, raising the question of whether there is anything exceptional about the supposed selective actions.We have used the voltage clamp technique to study the effect of fluoxetine on a neuronal, voltage-dependent potassium (K+) channel (RCK1; Kv1.1), expressed in Xenopus laevis oocytes. This channel subunit is abundantly expressed in the central nervous system and K+ channels containing this subunit are involved in the repolarization process of many types of neurones.Blockade of the K+ currents by fluoxetine was found to be use- and dose-dependent. Wash-out of this compound could not be achieved. Fluoxetine did not affect the ion selectivity of this K+ channel, as the reversal potential was unaltered.Slowing of both activation and deactivation kinetics of the channel by fluoxetine was observed, including tail current crossover upon repolarization.Hodgkin-Huxley type of models and more generalized Markov chain models were used to fit the kinetics of the data. Based upon a Markov kinetic scheme, our data can be interpreted to mean that blockade of fluoxetine consists of two components: a voltage-independent occurring in the last closed, but available state of the channel, and a voltage-dependent occurring in the open state.This study describes the first biophysical working model for the mechanism of action of fluoxetine on a neuronal, voltage-dependent K+ channel, RCK1. Although this channel is not very potently blocked by fluoxetine when expressed in oocytes, this study may help us to understand some of the clinical symptoms seen with elevated serum concentrations of this SSRI. PMID:9421290

  12. Acute aortic syndromes: definition, prognosis and treatment options.

    PubMed

    Carpenter, S W; Kodolitsch, Y V; Debus, E S; Wipper, S; Tsilimparis, N; Larena-Avellaneda, A; Diener, H; Kölbel, T

    2014-04-01

    Acute aortic syndromes (AAS) are life-threatening vascular conditions of the thoracic aorta presenting with acute pain as the leading symptom in most cases. The incidence is approximately 3-5/100,000 in western countries with increase during the past decades. Clinical suspicion for AAS requires immediate confirmation with advanced imaging modalities. Initial management of AAS addresses avoidance of progression by immediate medical therapy to reduce aortic shear stress. Proximal symptomatic lesions with involvement of the ascending aorta are surgically treated in the acute setting, whereas acute uncomplicated distal dissection should be treated by medical therapy in the acute period, followed by surveillance and repeated imaging studies. Acute complicated distal dissection requires urgent invasive treatment and thoracic endovascular aortic repair has become the treatment modality of choice because of favorable outcomes compared to open surgical repair. Intramural hematoma, penetrating aortic ulcers, and traumatic aortic injuries of the descending aorta harbor specific challenges compared to aortic dissection and treatment strategies are not as uniformly defined as in aortic dissection. Moreover these lesions have a different prognosis. Once the acute period of aortic syndrome has been survived, a lifelong medical treatment and close surveillance with repeated imaging studies is essential to detect impending complications which might need invasive treatment within the short-, mid- or long-term.

  13. Fluoxetine pretreatment effects pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, ECSTASY) in rat.

    PubMed

    Upreti, Vijay V; Eddington, Natalie D

    2008-04-01

    Fluoxetine has been shown to provide protection from MDMA induced long term neurotoxicity. The purpose of this investigation is to evaluate the pharmacokinetic drug interaction between MDMA and fluoxetine and also to determine the role of P-glycoprotein (P-gp) on mediating drug-drug interactions with MDMA. Bi-directional transport studies were conducted across MDCK-MDR1 and Caco-2 monolayers. MDMA brain and plasma levels were measured in P-gp deficient [mdr1a(-/-)] and normal [mdr1a(+/+)] mice after a 5 mg/kg i.p. dose of MDMA. Sprague-Dawley rats were pretreated with fluoxetine (4 days, 10 mg/kg, i.p.) or saline followed by MDMA (10 mg/kg, p.o.) and brain and plasma samples were collected over 10 h. MDMA and its active metabolite MDA were quantified using a HPLC method with fluorescence detection. In transport studies MDMA exhibited high permeability with essentially unpolarized transport. No significant difference in MDMA and MDA brain levels were seen in P-gp deficient versus normal mice. Pretreatment of rats with fluoxetine resulted in an increase in MDMA (1.4-fold) and MDA (1.5-fold) exposure in both brain and plasma. Elimination half-life was increased for MDMA (2.4 vs. 4.9 h) and MDA (1.8 vs. 8.2 h) with fluoxetine pretreatment. P-gp does not play a physiologically relevant role in absorption and distribution of MDMA, hence this transporter may not have a role in drug-drug interactions with MDMA. Fluoxetine pretreatment to provide protection from MDMA induced long term neurotoxicity decreases elimination of MDMA and MDA and may lead to enhanced risk of MDMA acute toxic effects. Overall, our results indicate that caution need to be practiced when recommending fluoxetine as an agent to provide protection from MDMA induced long term neurotoxicity.

  14. Effects of fluoxetine administration on regional galanin expression in obese Zucker rat hypothalamus.

    PubMed

    Churruca, Itziar; Portillo, María P; Gutiérreza, Arantza; Casis, Luis; Macarulla, María Teresa; Zarate, Jon; Echevarría, Enrique

    2004-06-01

    The aim of the present work was to study the potential involvement of hypothalamic galanin system in the anorectic mechanism of fluoxetine in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. Significant decreases in food intake, final body weight and total body fat were observed after fluoxetine treatment. Although fluoxetine-treated rats showed a decrease in urine elimination, this effect was not enough to compensate decreased water intake, leading to dehydration, as showed by decreased body water content. Chronic fluoxetine administration increased the numbers of galanin positively immunostained neural cells in medial and lateral preoptic areas, lateral hypothalamic area and paraventricular nucleus (rostral and magnocellular regions), without changes in dorsomedial, ventromedial, supraoptic, suprachiasmatic and arcuate nuclei. Taken into account that galanin stimulates appetite, these results could represent rather a compensatory response against reduced food intake than a direct anorectic mechanism. Changes in the magnocellular region of the hypothalamic paraventricular nucleus suggest a role for galanin neural circuits at this level in fluoxetine-induced hydro-osmotic impairment.

  15. The antidepressant fluoxetine induces necrosis by energy depletion and mitochondrial calcium overload.

    PubMed

    Charles, Emilie; Hammadi, Mehdi; Kischel, Philippe; Delcroix, Vanessa; Demaurex, Nicolas; Castelbou, Cyril; Vacher, Anne-Marie; Devin, Anne; Ducret, Thomas; Nunes, Paula; Vacher, Pierre

    2017-01-10

    Selective Serotonin Reuptake Inhibitor antidepressants, such as fluoxetine (Prozac), have been shown to induce cell death in cancer cells, paving the way for their potential use as cancer therapy. These compounds are able to increase cytosolic calcium concentration ([Ca2+]cyt), but the involved mechanisms and their physiological consequences are still not well understood. Here, we show that fluoxetine induces an increase in [Ca2+]cyt by emptying the endoplasmic reticulum (ER) through the translocon, an ER Ca2+ leakage structure. Our data also show that fluoxetine inhibits oxygen consumption and lowers mitochondrial ATP. This latter is essential for Ca2+ reuptake into the ER, and we postulated therefore that the fluoxetine-induced decrease in mitochondrial ATP production results in the emptying of the ER, leading to capacitative calcium entry. Furthermore, Ca2+ quickly accumulated in the mitochondria, leading to mitochondrial Ca2+ overload and cell death. We found that fluoxetine could induce an early necrosis in human peripheral blood lymphocytes and Jurkat cells, and could also induce late apoptosis, especially in the tumor cell line. These results shed light on fluoxetine-induced cell death and its potential use in cancer treatment.

  16. Fluoxetine Enhances Neurogenesis in Aged Rats with Cortical Infarcts, but This is not Reflected in a Behavioral Recovery.

    PubMed

    Sun, Xiaoyu; Zhou, Zhike; Liu, Tingting; Zhao, Mei; Zhao, Shanshan; Xiao, Ting; Jolkkonen, Jukka; Zhao, Chuansheng

    2016-02-01

    Age is associated with poor outcome and impaired functional recovery after stroke. Fluoxetine, which is widely used in clinical practice, can regulate hippocampal neurogenesis in young rodents. As the rate of neurogenesis is dramatically reduced during aging, we studied the effect of post-stroke fluoxetine treatment on neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of dentate gyrus (DG) and whether this would be associated with any behavioral recovery after the cortical infarct in aged rats. Aged rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Focal cortical ischemia was induced by intracranial injection of vasoconstrictive peptide, endothelin-1 (ET-1). Fluoxetine was administered in the drinking water for 3 weeks starting 1 week after ischemia at a dose of 18 mg/kg/day. Behavioral recovery was evaluated on post-stroke days 29 to 31 after which the survival rate and fate of proliferating cells in the SVZ and DG were assessed by immunohistochemistry. Apoptosis was measured with the TUNEL assay. The results indicated that chronic fluoxetine treatment after stroke enhanced the proliferation of newborn neurons in the SVZ, but not in SGZ, and it suppressed perilesional apoptosis. Fluoxetine treatment did not affect the survival or differentiation of newly generated cells in the SVZ i.e., the enhanced neurogenesis was not translated into a behavioral outcome.

  17. Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats.

    PubMed

    Abdel Salam, Omar M E

    2004-09-01

    The effect of the selective serotonin reuptake inhibitors, fluoxetine and sertraline on basal, secretagogues (histamine or bethanechol)- and distention-stimulated gastric acid secretion was investigated in the urethane-anaesthetised acute gastric fistula rat. Gastric acid secretion was measured by flushing of the gastric contents with saline every 15 min. Fluoxetine (10 or 20 mg kg(-1), i.p.) produced a dose-dependent increase in basal gastric acid secretion. These stimulatory effects were abolished by vagotomy. Intraperitoneally administered sertraline also stimulated gastric acid secretion. The stimulatory effect of lower doses (5 mg kg(-1)) of sertraline was similar to that of the higher (30 mg kg(-1)) doses. The gastric secretory response to i.p. sertraline was long lasting (greater than 60 min), and blocked by vagotomy. Intraperitoneally administered fluoxetine (10 or 20 mg kg(-1)) or sertraline (5 mg kg(-1)) also increased gastric secretion induced by histamine, bethanechol or distention. The fluoxetine or sertraline stimulatory effects of histamine-induced acid secretion were abolished by vagotomy. Data indicate a stimulatory effect for fluoxetine and sertraline mediated by vagal nerve on gastric acid secretion in urethane-anaesthetised rats.

  18. An Exploratory Analysis of the Impact of Family Functioning on Treatment for Depression in Adolescents

    ERIC Educational Resources Information Center

    Feeny, Norah C.; Silva, Susan G.; Reinecke, Mark A.; McNulty, Steven; Findling, Robert L.; Rohde, Paul; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; Pathak, Sanjeev M.; May, Diane E.; Kennard, Betsy D.; Simons, Anne D.; Wells, Karen C.; Robins, Michele; Rosenberg, David; March, John S.

    2009-01-01

    This article explores aspects of family environment and parent-child conflict that may predict or moderate response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive behavioral therapy, their combination, or placebo. Outcomes were Week 12 scores on measures of depression and global impairment. Of…

  19. Treatment for acute asthma in the Emergency Department: practical aspects.

    PubMed

    Urso, D L

    2010-03-01

    This article describes the management of acute asthma exacerbation in the Emergency Department (ED). An asthma exacerbation can be defined as clinical worsening of disease or an asymptomatic decrease in peak flows. Acute exacerbations of asthma may represent reactions to airway irritants or failures of chronic treatment. Hospitalizations and ED visits account for a large proportion of the health-care cost burden of asthma. The assessment of an asthma exacerbation constitutes a process with two different dimensions: to determine the severity of attack, and to evaluate the response to treatment. The principal goals of managing an asthma acute exacerbation may be summarized as maintenance of adequate arterial oxygen saturation with supplemental oxygen, relief of airflow obstruction with repetitive administration of short acting beta-2 agonists (SABA), and treatment of airway inflammation with systemic corticosteroids (CS) to prevent future relapses. SABA, oxygen, and CS form the basis of management of acute asthma exacerbation but a role is emerging for anthicolinergics.

  20. Diagnosis and treatment of acute bronchitis.

    PubMed

    Albert, Ross H

    2010-12-01

    Cough is the most common symptom bringing patients to the primary care physician's office, and acute bronchitis is usually the diagnosis in these patients. Acute bronchitis should be differentiated from other common diagnoses, such as pneumonia and asthma, because these conditions may need specific therapies not indicated for bronchitis. Symptoms of bronchitis typically last about three weeks. The presence or absence of colored (e.g., green) sputum does not reliably differentiate between bacterial and viral lower respiratory tract infections. Viruses are responsible for more than 90 percent of acute bronchitis infections. Antibiotics are generally not indicated for bronchitis, and should be used only if pertussis is suspected to reduce transmission or if the patient is at increased risk of developing pneumonia (e.g., patients 65 years or older). The typical therapies for managing acute bronchitis symptoms have been shown to be ineffective, and the U.S. Food and Drug Administration recommends against using cough and cold preparations in children younger than six years. The supplement pelargonium may help reduce symptom severity in adults. As patient expectations for antibiotics and therapies for symptom management differ from evidence-based recommendations, effective communication strategies are necessary to provide the safest therapies available while maintaining patient satisfaction.

  1. [New options in the treatment of acute heart failure].

    PubMed

    Link, A; Böhm, M

    2014-06-01

    Acute heart failure is defined as the acute onset of symptoms due to hear failure necessitating emergency therapy. The in-hospital mortality rate ranges up to 10 % and in cardiogenic shock is 50-70 %. In acute heart failure, rapid diagnosis and causal therapy are necessary to avoid cardiogenic shock. In cases of acute coronary syndromes, primary percutaneous intervention should be performed immediately. Medical and apparative treatment strategies focus on decreasing pulmonary congestion, afterload, and neurohormonal activation in order to improve hemodynamics and reduce symptoms of dyspnea. In contrast to chronic heart failure, no medical therapy has been able to reduce mortality rates in acute heart failure. However, new medical therapies should at least improve clinical symptoms of congestion and favorably reduce cardiovascular events, re-hospitalization, and mortality rates.

  2. Effects of fluoxetine on memory under forced treadmill exercise conditions in male rats

    PubMed Central

    Jafary, Leila; Reisi, Parham; Naghsh, Nooshin

    2015-01-01

    Background: Studies show inconsistent effects of forced exercise on cognitive processes. These differences are probably due to the stress of coercion in forced exercise. Because fluoxetine is used to treat complications caused by stress, this study aimed to evaluate the effects of fluoxetine on memory in rats under forced treadmill exercise. Materials and Methods: Experimental groups were the control, the control exercise, the fluoxetine, and the fluoxetine exercise. The exercise program was treadmill running at 22 m/min, 0° inclination for 50 min/day, 6 days/week, for 4 weeks. Fluoxetine (5 mg/kg) was injected 30 min before treadmill. Morris water maze and passive avoidance learning tests were used for evaluation of memory. Acquisition phase of both tests were performed before interventions and memory was evaluated 1-day and 1-week after the last session of exercise and treatments. Results: Our data showed that forced exercise impaired performance in passive avoidance learning test (P < 0.05 and P < 0.01, 1-day and 1-week after the last session of exercise and treatments, respectively). Spatial memory was only impaired after 1-week in the exercise group. Fluoxetine improved spatial memory after 1-day in the control group. However, it had no significant effects on memory in the exercise group. Conclusion: The data correspond to the possibility that forced treadmill exercise can cause stress, and thereby cause damage to memory. The present results suggest that although fluoxetine may improve memory in intact rats but it cannot prevent damages that are caused by forced exercise. PMID:26645020

  3. Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex

    PubMed Central

    Guirado, Ramon; La Terra, Danilo; Bourguignon, Mathieu; Carceller, Hector; Umemori, Juzoh; Sipilä, Pia; Nacher, Juan; Castrén, Eero

    2016-01-01

    Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of interneurons but also has been shown to play a role in the onset of critical periods during development. We have here used ocular dominance plasticity in the mouse visual cortex as a model to investigate whether removal of PSA might influence the Fluoxetine-induced plasticity. We demonstrate that PSA removal in the adult visual cortex alters neither the baseline ocular dominance, nor the fluoxetine-induced shift in the ocular dominance. We also show that both chronic Fluoxetine treatment and PSA removal independently increase the basal FosB expression in parvalbumin (PV) interneurons in the primary visual cortex. Therefore, our data suggest that although PSA-NCAM regulates inhibitory circuitry, it is not required for the reactivation of juvenile-like plasticity triggered by Fluoxetine. PMID:26903807

  4. New Framework To Diagnose the Direct Disposal of Prescribed Drugs in Wastewater - A Case Study of the Antidepressant Fluoxetine.

    PubMed

    Petrie, Bruce; Youdan, Jane; Barden, Ruth; Kasprzyk-Hordern, Barbara

    2016-04-05

    Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy).

  5. Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

    PubMed Central

    Rayen, Ine; van den Hove, Daniël L.; Prickaerts, Jos; Steinbusch, Harry W.; Pawluski, Jodi L.

    2011-01-01

    Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity. PMID:21912658

  6. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  7. Omega-3 Fatty Acid Deficient Male Rats Exhibit Abnormal Behavioral Activation in the Forced Swim Test Following Chronic Fluoxetine Treatment: Association with Altered 5-HT1A and Alpha2A Adrenergic Receptor Expression

    PubMed Central

    Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K.

    2014-01-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n=34) or without (DEF, n=30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n=14) and DEF (n=12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (−26%, p=0.0001) and DEF+FLX (−32%, p=0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF+FLX rats exhibited significantly greater climbing behavior compared with CON+FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF+FLX rats exhibited significant elevations in climbing behavior. DEF+FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON+FLX rats. DEF+FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats. PMID:24360505

  8. [The fibrinolytic treatment with urokinase of acute arterial thrombosis].

    PubMed

    Ballester, A; Donato di Paola, M; Saccà, A; Cappello, I; D'Addato, M

    1993-01-01

    We present our experiences on 86 patients with acute arterial thrombosis of the legs, undergoing a fibrinolytic treatment with urokinase. Results from the treatment are analyzed according to: the administration way (systemic, locoregional, intrathrombotic), the level of thrombosis (upper or lower legs), the associated morbidity and mortality.

  9. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    ERIC Educational Resources Information Center

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  10. Painless acute pancreatitis associated with sorafenib treatment: a case report.

    PubMed

    Kobayashi, Yasuyuki; Kanemitu, Toshiyuki; Kamoto, Akihito; Satoh, Mototaka; Mori, Naoki; Sekii, Kenichiro; Yoshioka, Toshiaki; Itatani, Hiroaki; Fujimoto, Takashi

    2011-06-01

    Sorafenib is a multikinase inhibitor that is used for the treatment of metastatic renal-cell carcinoma. We report the case of a patient with painless acute pancreatitis associated with sorafenib treatment. The patient was a 71-year-old man who had undergone surgery for left renal carcinoma and tumor thrombus in the inferior vena cava and right atrium (IVC-RA). After a follow-up period of 3 years, he developed right adrenal metastasis and received interferon (IFN)-alpha treatment. One year later, progression of the adrenal metastasis was observed, and he was admitted to a hospital for treatment with sorafenib, which was administered at a dose of 800 mg/day. Two weeks later, he developed painless acute pancreatitis associated with sorafenib treatment. Thereafter, sorafenib treatment was discontinued, and he was treated with conservative therapy. Three weeks later, he was discharged. Even though painless acute pancreatitis associated with sorafenib treatment is rare, the possible development of painless acute pancreatitis in patients undergoing sorafenib treatment must be kept in mind.

  11. Pediatric Acute Bacterial Sinusitis: Diagnostic and Treatment Dilemmas.

    PubMed

    Fang, Andrea; England, Jasmin; Gausche-Hill, Marianne

    2015-11-01

    Acute bacterial sinusitis (ABS) is a common complication of a simple upper respiratory infection. Acute bacterial sinusitis and an upper respiratory infection, however, have different management plans. This article will help clinicians establish when a diagnosis of ABS can be made based on the latest guidelines from the American Academy of Pediatrics. Also covered will be the pathophysiology of ABS, the role of diagnostic imaging, the recognition of complications of ABS, and treatment options.

  12. Interaction of fluoxetine with phosphatidylcholine liposomes.

    PubMed

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto

    2005-10-22

    Fluoxetine (Prozac) is one of the latest of a new generation of antidepressants, approved by FDA in 2002. The interactions of fluoxetine with multilamellar liposomes of pure phosphatidylcholine (PC) or containing cholesterol 10% molar were studied as a function of the lipid chain lengths, using differential scanning calorimetry and spin labelling EPR techniques. The DSC profiles of the gel-to-fluid state transition of liposomes of DMPC (C14:0) are broadened and shifted towards lower temperatures at increasing dopant concentrations and, with less than 10% fluoxetine, any detectable transition is destroyed. The broadened profiles and the lowered transition temperatures demonstrate that both the size and the packing of the cooperative units undergoing the transition are modified by fluoxetine, leading to a looser and more flexible bilayer. No phase separation was observed. The effects of fluoxetine on the thermotropic phase behaviour of DPPC (C16:0) and, even more, of DSPC (C18:0) are different from that of DMPC. In fact, in the former cases, two peaks appeared at increasing dopant concentrations, suggesting the occurrence of a phase separation phenomenon, which is a sign of a binding of fluoxetine in the phosphate region. In cholesterol containing membranes, fluoxetine, even at low concentrations, leads to a general corruption of the membrane, both in terms of packing and cooperativity, and the formation of any new phase is no longer observable. EPR spectra reflect the disordered motion of acyl chains in the bilayer. It was found that fluoxetine lowers the order of the lipid chains mainly in correspondence of the fifth carbon position of SASL, indicating a possible accumulation near the interfacial region.

  13. Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.

    PubMed

    Chen, Fenghua; du Jardin, Kristian Gaarn; Waller, Jessica A; Sanchez, Connie; Nyengaard, Jens R; Wegener, Gregers

    2016-02-01

    Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.

  14. [Cerebrolysin in treatment of acute ischemic stroke].

    PubMed

    Domzał, T; Zaleska, B

    1995-01-01

    Cerebrolysin is composed of low molecular peptides and free amino-acids and as a nootropic drug it administered in various diseases of central nervous system. In an open clinical trial patients with acute ischaemic stroke in the region of the middle cerebral artery, were treated. Cerebrolysin was administered as intravenous infusion in daily dose of 15 ml during 21 days. Recovery in 10 patients and improvement in 3 was obtained and only one patient died. The results were compared to the large group of 108 patients treated earlier with other drugs. Therapeutic effect was similar in all groups.

  15. Mice increased target biting behaviors 24 hours after co-administration of alcohol and fluoxetine.

    PubMed

    Mamiya, Ping Chao; Matray-Devoti, Judith; Fisher, Hans; Wagner, George C

    2017-02-10

    Increased alcohol consumption has been linked to social isolation. Individuals showed heightened aggression following social isolation. Animals treated with alcohol following social separation showed higher aggression and lower serotonin transmission. Although reduced serotonin transmission in the brain may be related to alcohol induced heightened aggression, it remains unclear whether there are specific brain regions where changes in serotonin transmission are critical for animal aggression following alcohol treatment. In the present study, we isolated mice for 4 - 6 weeks and injected them with alcohol, fluoxetine and alcohol with fluoxetine. We studied their aggression by using two types of behavioral paradigms: isolation-induced attack behavior towards a naïve mouse in a neutral cage, or shock-induced target biting aggression. We observed that alcohol administered at 500 mg/kg significantly increased animal attack behaviors towards naïve mice 30 minutes after injections. This dose of alcohol co-administered with a low dose of fluoxetine (2 mg/kg) further increased the attack behaviors, but with higher doses of fluoxetine decreased the attack behaviors. Alcohol administered at a dose of 1,000 mg/kg significantly decreased the shock-induced target biting rates 24 hours after injections. Interestingly, we observed a significant increase in target biting rates when alcohol was co-administered with fluoxetine at a dose of 16 mg/kg 24 hours after injections. We also observed the same heightened target biting rates when animals were injected with fluoxetine alone. This heightened biting attack engendered by the fluoxetine (alone or in combination with the alcohol) occurred at a time when brain serotonin activity was reduced by these drugs in the frontal lobe and hypothalamus. These observations indicate that heightened biting attack behavior may be associated with reduced serotonergic activity in brain regions regulating aggression.

  16. Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats.

    PubMed

    Salem Sokar, Samia; Elsayed Elsayad, Mageda; Sabri Ali, Hend

    2016-09-01

    Research in the treatment of gastric ulcer has involved the investigation of new alternatives, such as anti-depressant drugs. The present study was designed to investigate the gastroprotective effects of fluoxetine against indomethacin and alcohol induced gastric ulcers in rats and the potential mechanisms of that effect. Fluoxetine (20 mg/kg) was administered IP for 14 days. For comparative purposes, other rats were treated with ranitidine (30 mg/kg). Thereafter, after 24 h of fasting, INDO (100 mg/kg) or absolute alcohol (5 ml/kg) was administered to all rats (saline was administered to naïve controls) and rats in each group were sacrificed 5 h (for INDO rats) or 1 h (for alcohol rats) later. Macroscopic examination revealed that both fluoxetine and ranitidine decreased ulcer scores in variable ratios, which was supported by microscopic histopathological examination. Biochemical analysis of fluoxetine- or ranitidine-pre-treated host tissues demonstrated reductions in tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) levels and concomitant increases in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents. Fluoxetine, more than ranitidine, also resulted in serotonin and histamine levels nearest to control values. Moreover, immuno-histochemical analysis showed that fluoxetine markedly enhanced expression of cyclo-oxygenases COX-1 and COX-2 in both models; in comparison, ranitidine did not affect COX-1 expression in either ulcer model but caused moderate increases in COX-2 expression in INDO-induced hosts and high expression in alcohol-induced hosts. The results here indicated fluoxetine exhibited better gastroprotective effects than ranitidine and this could be due to anti-secretory, anti-oxidant, anti-inflammatory and anti-histaminic effects of the drug, as well as a stabilization of gastric serotonin levels.

  17. Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex

    PubMed Central

    Ruiz-Perera, L.; Muniz, M.; Vierci, G.; Bornia, N.; Baroncelli, L.; Sale, A.; Rossi, F.M.

    2015-01-01

    The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity, and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex, and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain. PMID:26205348

  18. Effects of psychological stress and fluoxetine on development of oral candidiasis in rats.

    PubMed

    Núñez, María J; Novío, Silvia; Suárez, Juan Antonio; Balboa, José; Freire-Garabal, Manuel

    2010-04-01

    Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.

  19. Acute treatment of mania: an update on new medications.

    PubMed

    Gajwani, Prashant; Kemp, David E; Muzina, David J; Xia, Guohua; Gao, Keming; Calabrese, Joseph R

    2006-12-01

    Acute mania is frequently a medical emergency requiring hospitalization for behavioral control, rapid resolution of irritability, agitation, de-escalation of mood, and decreasing of risk-taking behavior. Lithium efficacy in the management of acute mania was reported in 1949 and approved by the US Food and Drug Administration (FDA) in 1970. Chlorpromazine, from the class of typical antipsychotics, was approved for treatment of bipolar disorder in 1973. Typical antipsychotics were frequently used alone and as adjunct for the treatment of bipolar mania for the next 2 decades. Divalproex was approved by the FDA for the treatment of acute mania in 1994. Since the approval of olanzapine in 2000, all five atypical antipsychotics, namely risperidone (2003), quetiapine (2004), ziprasidone (2004), and aripiprazole (2004), have been approved by the FDA for the management of acute mania. Clozapine is the only atypical antipsychotic not FDA approved for any phase of bipolar disorder. This article will systematically review some of the major studies published, randomized controlled monotherapy, and adjunct therapy trials involving five atypical antipsychotics and newer anticonvulsants for the treatment of acute bipolar mania.

  20. [Our experiences in the treatment of acute leukemias].

    PubMed

    Jelić, S; Dragović, M; Vidaković, B; Plecas, V

    1976-01-01

    This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.

  1. [CONSERVATIVE THERAPY IN THE COMPLEX TREATMENT OF ACUTE NECROTIZING PANCREATITIS].

    PubMed

    Khomyak, I V

    2015-07-01

    Developed and implemented a phased differentiated treatment tactics in acute necrotizing pancreatitis, based on the theory of phase course of acute pancreatitis. Treatment started with conservative measures. Applications developed set of measures allowed us to achieve recovery of 39.53% patients without any instrumental interventions performans, including diapevtycal. Laparotomy reduced frequency performance of 57.14%--in the control group to 33.07%--in the main. Mortality in the main group was 6.72%; complication rate decreased 2.26 times; postoperative mortality was 9.83%.

  2. 77 FR 61417 - Guidance for Industry on Acute Bacterial Sinusitis: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-09

    ...: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Acute Bacterial Sinusitis: Developing Drugs for Treatment.'' This guidance addresses FDA's... an indication for the treatment of acute bacterial sinusitis (ABS). This guidance finalizes...

  3. Fluoxetine Ameliorates Atopic Dermatitis-Like Skin Lesions in BALB/c Mice through Reducing Psychological Stress and Inflammatory Response

    PubMed Central

    Li, Yanxi; Chen, Long; Du, Yehong; Huang, Daochao; Han, Huili; Dong, Zhifang

    2016-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p.) significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4) and IL-13 in the spleen, as well as serum immunoglobulin E (IgE) in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic. PMID:27679577

  4. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex123

    PubMed Central

    Beshara, Simon; Beston, Brett R.; Pinto, Joshua G. A.

    2015-01-01

    Abstract Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity. PMID:26730408

  5. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.

    PubMed

    Beshara, Simon; Beston, Brett R; Pinto, Joshua G A; Murphy, Kathryn M

    2015-01-01

    Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.

  6. Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes.

    PubMed

    Tikhonova, M A; Alperina, E L; Tolstikova, T G; Bazovkina, D V; Di, V Y; Idova, G V; Kulikov, A V; Popova, N K

    2010-06-01

    ASC (Antidepressant-Sensitive Catalepsy) mice, bred for a high predisposition to catalepsy, are characterized by depression-like behavior and decreased immune responses. Chronic administration of fluoxetine, which is a selective serotonin reuptake inhibitor antidepressant widely used in clinical practice, to mice of this strain weakened catalepsy and normalized the number of rosette-forming cells in the spleen. In mice of the parental cataleptic strain CBA/Lac, fluoxetine had no effect on the level of catalepsy or the immune response. Analysis of the effects of fluoxetine on the functional activity of 5-HT(1A) and 5-HT(2A) receptors, and the expression of 5-HT(1A) receptor genes in the frontal cortex and midbrain and 5-HT(2A) receptors in the frontal cortex, as well as the tryptophan hydroxylase-2 and the serotonin transporter genes in the midbrain showed that the antidepressant had no effect on these parameters in ASC mice, but decreased the functional activity of 5-HT(2A) receptors in CBA/Lac mice. The possibility that the actions of fluoxetine on catalepsy and the immune response in mice with depression-like states are mediated via other serotoninergic mechanisms is discussed.

  7. Treatment of adult acute lymphoblastic leukaemia.

    PubMed

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  8. Octreotide treatment in patients with severe acute pancreatitis.

    PubMed

    Paran, H; Mayo, A; Paran, D; Neufeld, D; Shwartz, I; Zissin, R; Singer, P; Kaplan, O; Skornik, Y; Freund, U

    2000-11-01

    We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case-control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis.

  9. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

    PubMed

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

    2015-12-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders.

  10. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress

    PubMed Central

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J.; Robison, A.J.

    2015-01-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's “reward circuitry,” consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression – the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus – in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 hours following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. PMID:26164345

  11. Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: outcome after long-term follow-up.

    PubMed

    Peselow, Eric D; Tobia, Gabriel; Karamians, Reneh; Pizano, Demetria; IsHak, Waguih William

    2015-02-28

    The acute efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD) is well established; however their role in longer-term prevention of recurrence remains unconfirmed. This study aims at examining: the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up, the effect of concomitant cognitive behavioral therapy (CBT), and the predictors of outcome. In a prospective cohort study, 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine, escitalopram, sertraline and paroxetine-were followed up over several years. During an average follow-up period of 34.5 months, 76.5% of patients experienced MDD recurrence. Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant. The prophylactic efficacy for SSRI-only treatment was limited, with a recurrence rate of 82.0%, compared to 59.0% of patient recurrence rate in concomitant Cognitive Behavioral Therapy (CBT). The relatively small size of the CBT group and the lack of randomization may undermine the extrapolation of its findings to clinical practice. Nevertheless, the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence.

  12. Early rehabilitative treatment for pediatric acute disseminated encephalomyelitis: case report.

    PubMed

    Carlisi, E; Pavese, C; Mandrini, S; Carenzio, G; Dalla Toffola, E

    2015-06-01

    Although the diagnosis of and therapy for acute disseminated encephalomyelitis (ADEM) have been extensively investigated, the role of rehabilitation in modifying its functional outcome has received little attention in the literature so far. We report a case of pediatric ADEM who showed complete functional recovery following early rehabilitative treatment, started in the Intensive Care Unit.

  13. Validity of Sudden Gains in Acute Phase Treatment of Depression

    ERIC Educational Resources Information Center

    Vittengl, Jeffrey R.; Clark, Lee Anna; Jarrett, Robin B.

    2005-01-01

    The authors examined the validity of sudden gains identified with T. Z. Tang and R. J. DeRubeis's (1999) method in 2 clinical data sets that involved treatment of major depressive disorder (N=227). Sudden gains replicated among self- and clinician reports of depressive symptoms and predicted better psychosocial functioning at the acute phase…

  14. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  15. Treatment of acute lymphoblastic leukaemia (ALL).

    PubMed

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  16. Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems.

    PubMed

    Düsman, E; Almeida, I V; Mariucci, R G; Mantovani, M S; Vicentini, V E P

    2014-01-28

    Fluoxetine, commonly known as Prozac, is the first representative of the so-called new generation of antidepressants that promise efficacy, with few side effects, against deep depression, nervous bulimia, and anxiety. As there is a growing number of people suffering from anxiety and depression; consequently, the use of fluoxetine is also increasing. Verifying absence of drug effects such as cytotoxicity or mutagenicity is of great importance. Certain vitamins, such as vitamin A (retinol, retinoids) and vitamin C (ascorbic acid) protect and are extremely active against mutagens. We evaluated the cytotoxic and mutagenic activity of fluoxetine, with and without concomitant administration of vitamin A or C, in Allium cepa meristem cells and Wistar rat bone marrow cells. The A. cepa meristem cells showed fluoxetine cytotoxicity; concomitant treatment with vitamin A or C proved non-protective. Treatment of Wistar rats with fluoxetine intraperitoneally or via gavage did not affect cell division or cause clastogenic effects. Vitamin A and C did not affect the cytotoxicity or mutagenicity of fluoxetine in the rat cells.

  17. 1H NMR-based metabolic profiling reveals the effects of fluoxetine on lipid and amino acid metabolism in astrocytes.

    PubMed

    Bai, Shunjie; Zhou, Chanjuan; Cheng, Pengfei; Fu, Yuying; Fang, Liang; Huang, Wen; Yu, Jia; Shao, Weihua; Wang, Xinfa; Liu, Meiling; Zhou, Jingjing; Xie, Peng

    2015-04-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte's lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.

  18. [Fluoxetine: an update of its use in major depressive disorder in adults].

    PubMed

    Gourion, D; Perrin, E; Quintin, Ph

    2004-01-01

    which a SSRI exerts its anti-depressant activity remains uncertain. The therapeutic response in major depression for SSRIs (ie 15-20 days) maybe due to a progressive desensitization of somatodendritic 5-HT autoreceptors in the midbrain raphe nucleus. On the other hand, it has also been postulated that 5-HT is a modulator of several neurophysiological pathways, including dopamine, noradrenaline, but also neurotrophic factors, intra-cytoplasmic phosphorylations and nuclear genes expression. Therapeutic activity of SSRIs may finally results in a complex modulation and homeostasis between monoaminergic neurotransmisson and neuronal plasticity. In term of health-care, the introduction of fluoxetine and other SSRIs in the 1980s has radically changed the treatment of depressive disorder worldwide and they have emerged as the first line of treatment for depressive disorders. The efficacy of fluoxetine is now well established in the treatment of major depressive disorder. Indeed, this efficacy has been assessed in numerous clinical controlled trials involving patients with major depressive disorders. Meta-analysis were carried out and confirmed that fluoxetine was as effective as the tricyclic antidepressants, and appeared more effective than placebo in improving the symptoms of depression. However, there is no scientific evidence to suggest that any one SSRI is more effective than another, but not all patients respond to the same agent. Looking to the future, we need further comparative studies of the SSRIs with the next generation of antidepressants such as 5-HT noradrenaline reuptake inhibitors (SNRIs, Venlafaxine). Actually, it is interesting to note that, whereas the emphasis with the SSRIs has been on their selectivity, recent developments have tended to move towards less selective agents, and now to other neurobiological pathways (ie neurotrophic factors). Finally, fluoxetine, in common with other SSRIs, remains today a first-line treatment option for major depressive

  19. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  20. [Monitorering and complications by conservative treatment of severe acute pancreatitis].

    PubMed

    Novovic, Srdan; Malmstrøm, Marie Louise; Møller Andersen, Anders; Jørgensen, Lars Nannestad; Philipsen, Else; Schmidt, Palle Nordblad; Hansen, Mark Berner

    2013-05-20

    Severe acute pancreatitis (SAP) is associated with a high morbidity and a mortality risk of up to 20%. Although much progress has occurred during the latest couple of years, there are still some major controversies on important issues such as monitoring, fluid therapy, antibiotic treatment, and nutrition. In this article we describe the underlying, pathophysiologic mechanisms responsible for organ failure in SAP, and the rationale for monitoring and conservative treatment of SAP.

  1. Fluoxetine elevates allopregnanolone in female rat brain but inhibits a steroid microsomal dehydrogenase rather than activating an aldo-keto reductase

    PubMed Central

    Fry, J P; Li, K Y; Devall, A J; Cockcroft, S; Honour, J W; Lovick, T A

    2014-01-01

    Background and Purpose Fluoxetine, a selective serotonin reuptake inhibitor, elevates brain concentrations of the neuroactive progesterone metabolite allopregnanolone, an effect suggested to underlie its use in the treatment of premenstrual dysphoria. One report showed fluoxetine to activate the aldo-keto reductase (AKR) component of 3α-hydroxysteroid dehydrogenase (3α-HSD), which catalyses production of allopregnanolone from 5α-dihydroprogesterone. However, this action was not observed by others. The present study sought to clarify the site of action for fluoxetine in elevating brain allopregnanolone. Experimental Approach Adult male rats and female rats in dioestrus were treated with fluoxetine and their brains assayed for allopregnanolone and its precursors, progesterone and 5α-dihydroprogesterone. Subcellular fractions of rat brain were also used to investigate the actions of fluoxetine on 3α-HSD activity in both the reductive direction, producing allopregnanolone from 5α-dihydroprogesterone, and the reverse oxidative direction. Fluoxetine was also tested on these recombinant enzyme activities expressed in HEK cells. Key Results Short-term treatment with fluoxetine increased brain allopregnanolone concentrations in female, but not male, rats. Enzyme assays on native rat brain fractions and on activities expressed in HEK cells showed fluoxetine did not affect the AKR producing allopregnanolone from 5α-dihydroprogesterone but did inhibit the microsomal dehydrogenase oxidizing allopregnanolone to 5α-dihydroprogesterone. Conclusions and Implications Fluoxetine elevated allopregnanolone in female rat brain by inhibiting its oxidation to 5α-dihydroprogesterone by a microsomal dehydrogenase. This is a novel site of action for fluoxetine, with implications for the development of new agents and/or dosing regimens to raise brain allopregnanolone. PMID:25161074

  2. Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell

    SciTech Connect

    Chiou, S.-H. . E-mail: shchiou@vghtpe.gov.tw; Chen, S.-J. . E-mail: sjchen@vghtpe.gov.tw; Peng, C-H.; Chang, Y.-L.; Ku, H.-H.; Hsu, W.-M.; Ho, Larry L.-T.; Lee, C.-H.

    2006-05-05

    Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 {mu}M fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide-induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1{beta}, IL-6, and TNF-{alpha} in the culture medium of LPS-treated NSCs (p < 0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression.

  3. Endovascular treatment for acute pulmonary embolism in neurological patient

    PubMed Central

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-01-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  4. Antagonistic interactions between dexamethasone and fluoxetine modulate morphodynamics and expression of cytokines in astrocytes.

    PubMed

    Henkel, A W; Alali, H; Devassy, A; Alawadi, M M; Redzic, Z B

    2014-11-07

    The "plasticity hypothesis" proposes that major depression is caused by morphological and biochemical modifications in neurons and astrocytes and those beneficial pharmacological effects of selective-serotonin-reuptake-inhibitors (SSRI) are at least partially associated with modifications of cellular communications between these cells. In this study we examined effects of the antidepressant fluoxetine on cultured astrocytes that were, in some cases, pretreated with dexamethasone, a cortisol analog known to trigger depressive disorder. Primary rat astrocytes were purified and treated with dexamethasone and the SSRI fluoxetine in physiological concentrations so that both drugs did not affect cell viability. Expression of interleukin-2 (IL-2) and glia-derived-neurotrophic-factor (GDNF) were analyzed and monitored and cell viability, apoptosis, cluster formation, particle-removing capacity and cell mobility were also monitored. Pre-studies without any drugs on mixed neuron-astrocyte co-cultures suggested that astrocytes interacted with neurons and other brain cells in vitro by actively assembling them into clusters. Treatment of purified astrocytes with dexamethasone significantly decreased their mobility compared to controls but had no effect on cluster formation. Dexamethasone-treated cells removed fewer extracellular particles derived from dead cells and cell debris. Both effects were abolished by simultaneous application of fluoxetine. Intracellular IL-2 increased, while GDNF amount expression was diminished following dexamethasone treatment. Simultaneous administration of fluoxetine reversed dexamethasone-triggered IL-2 elevation but had no effect on decreased GDNF concentration. These results suggest that mobility and growth factor equilibrium of astrocytes are affected by dexamethasone and by fluoxetine and that fluoxetine could reverse some changes induced by dexamethasone.

  5. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    PubMed

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats.

  6. [State-of-the-art Treatment of Acute Stroke].

    PubMed

    Weber, R; Nordmeyer, H

    2015-11-01

    This article gives an overview about diagnostic imaging and treatment options of acute patients with ischemic and hemorrhagic stroke with emphasis on evidence from relevant studies published in the last 2 years. A computed tomography of the brain with CT-angiography should be the minimal standard imaging modality in acute ischemic stroke patients. Diffusion-weighted/imaging-fluid-attenuated inversion recovery (FLAIR)-mismatch magnetic resonance imaging can be useful in patients with wake-up stroke to select patients for recanalisation therapies. Systemic thrombolysis with rt-PA within 4.5 hours after symptom onset and mechanical thrombectomy with stent retrievers within 6 hours and proven occlusion of a large vessel in the anterior brain circulation are both evidence-based treatments. In contrast, there are no major therapeutic advances in patients with hemorrhagic stroke. The systolic blood pressure should be lowered < 140  mm Hg in these patients within one hour. Both acute ischemic and hemorrhagic stroke and patients with a transient ischemic attack should be monitored and treated on a stroke unit due to an improved outcome. A prophylactic antibiotic treatment and very early mobilization during the first 24 hours is not recommended in acute stroke patients.

  7. The antidepressant drugs fluoxetine and duloxetine produce anxiolytic-like effects in a schedule-induced polydipsia paradigm in rats: enhancement of fluoxetine's effects by the α2 adrenoceptor antagonist yohimbine.

    PubMed

    Prus, Adam J; Mooney-Leber, Sean M; Berquist, Michael D; Pehrson, Alan L; Porter, Nicholas P; Porter, Joseph H

    2015-08-01

    Similar to the time-course for treating depression, several weeks of administration are required for serotonin (5-HT) reuptake inhibitors to produce anxiolytic effects. Previous studies with the schedule-induced polydipsia paradigm (a putative preclinical anxiety model) have shown that repeated administration of antidepressant drugs is necessary to produce a suppression of polydipsia, which is interpreted as an anxiolytic-like effect. The present study sought to expand past findings by evaluating the selective 5-HT reuptake inhibitor (SSRI) fluoxetine and the 5-HT-norepinephrine reuptake inhibitor duloxetine in the schedule-induced polydipsia paradigm with rats. Dose combinations of the α2 adrenoceptor antagonist yohimbine with fluoxetine were also explored to determine whether α2 adrenoceptor antagonism could enhance the anxiolytic-like effects produced by an SSRI. Fluoxetine and duloxetine significantly reduced water intake over the course of daily administrations. Daily treatment with the combination of fluoxetine and yohimbine produced a significantly greater reduction in water intake than fluoxetine alone. The present results confirmed previous findings that inhibition of 5-HT reuptake reduces water consumption in this paradigm. The results for the α2 antagonist yohimbine (in combination with fluoxetine) also indicate that α2 adrenoceptor antagonism may significantly enhance anxiolytic-like effects of SSRIs.

  8. Treatment of acute experimental toxoplasmosis with investigational poloxamers.

    PubMed Central

    Krahenbuhl, J L; Fukutomi, Y; Gu, L

    1993-01-01

    Because of the limited chemotherapeutic approaches available to treat reactivated latent Toxoplasma gondii infection manifested as toxoplasmic encephalitis in AIDS patients, investigation of novel chemotherapeutic agents is warranted. Several poloxamers (nonionic block copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene) were tested for their abilities to alter the course of acute infection with a highly virulent T. gondii in mice. The effect varied markedly with the length of the constituent chains of the copolymers. The most effective preparations were highly effective when administered after infection and afforded remarkable protection against 10 to 1,000 100% lethal doses of T. gondii. Protection was dose dependent, and multiple treatments were more effective than single treatment. These preliminary findings warrant additional studies to determine whether this novel form of antitoxoplasma chemotherapy may prove promising in the treatment or prevention of acute toxoplasmic encephalitis in humans. PMID:8285605

  9. Treatment of hyperglycaemia in patients with acute stroke.

    PubMed

    Castilla-Guerra, L; Fernández-Moreno, M C; Hewitt, J

    2016-03-01

    The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke. Ultimately, patients who have presented with stroke should be screened for diabetes.

  10. Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective

    PubMed Central

    Shi, Shu-hai; Qi, Zhi-feng; Luo, Yu-min; Ji, Xun-ming; Liu, Ke Jian

    2016-01-01

    Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials. In this article, we review the current literatures on NBO treatment of acute ischemic stroke in preclinical and clinical studies and try to analyze and identify the key gaps or unknowns in our understanding about NBO. Based on these analyses, we provide suggestions for future studies. PMID:27867482

  11. [Treatment of patients with acute asthma exacerbation].

    PubMed

    Ostojić, Jelena; Mose, Jakov

    2009-01-01

    Asthma is a chronic inflammatory disease of the airways. The global prevalence of asthma ranges from 1% to 18% of the population, so it remains a common problem with enormous medical and economic impacts. In majority of patients, asthma can be well controlled with simple regimens of inhaled anti-inflammatory and bronchodilating medications. However, some patients tend to suffer from poorly controlled disease in terms of chronic symptoms with episodic severe exacerbations. Major factors that may be related to the emergency department visits and hospitalisation include prior severe attacks, nonadherence to therapeutic regimens, inadequate use of inhaled corticosteroids, poor self-management skills, frequent use of inhaled short-acting beta-agonists, cigarette smoking, poor socioeconomic status and age over 40 years. Severe exacerbations of asthma are life-threatening medical emergencies and require careful brief assesment, treatment according to current GINA (Global Initiative for Asthma) guidelines with periodic reassesment of patient's response to therapy usually in an emergency department.

  12. Fluoxetine Prevents Aβ1-42-Induced Toxicity via a Paracrine Signaling Mediated by Transforming-Growth-Factor-β1

    PubMed Central

    Caraci, Filippo; Tascedda, Fabio; Merlo, Sara; Benatti, Cristina; Spampinato, Simona F.; Munafò, Antonio; Leggio, Gian Marco; Nicoletti, Ferdinando; Brunello, Nicoletta; Drago, Filippo; Sortino, Maria Angela; Copani, Agata

    2016-01-01

    Selective reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, increase circulating Transforming-Growth-Factor-β1 (TGF-β1) levels in depressed patients, and are currently studied for their neuroprotective properties in Alzheimer’s disease. TGF-β1 is an anti-inflammatory cytokine that exerts neuroprotective effects against β-amyloid (Aβ)-induced neurodegeneration. In the present work, the SSRI, fluoxetine, was tested for the ability to protect cortical neurons against 1 μM oligomeric Aβ1-42-induced toxicity. At therapeutic concentrations (100 nM–1 μM), fluoxetine significantly prevented Aβ-induced toxicity in mixed glia-neuronal cultures, but not in pure neuronal cultures. Though to a lesser extent, also sertraline was neuroprotective in mixed cultures, whereas serotonin (10 nM–10 μM) did not mimick fluoxetine effects. Glia-conditioned medium collected from astrocytes challenged with fluoxetine protected pure cortical neurons against Aβ toxicity. The effect was lost in the presence of a neutralizing antibody against TGF-β1 in the conditioned medium, or when the specific inhibitor of type-1 TGF-β1 receptor, SB431542, was added to pure neuronal cultures. Accordingly, a 24 h treatment of cortical astrocytes with fluoxetine promoted the release of active TGF-β1 in the culture media through the conversion of latent TGF-β1 to mature TGF-β1. Unlike fluoxetine, both serotonin and sertraline did not stimulate the astrocyte release of active TGF-β1. We conclude that fluoxetine is neuroprotective against Aβ toxicity via a paracrine signaling mediated by TGF-β1, which does not result from a simplistic SERT blockade. PMID:27826242

  13. Fluoxetine Prevents Aβ1-42-Induced Toxicity via a Paracrine Signaling Mediated by Transforming-Growth-Factor-β1.

    PubMed

    Caraci, Filippo; Tascedda, Fabio; Merlo, Sara; Benatti, Cristina; Spampinato, Simona F; Munafò, Antonio; Leggio, Gian Marco; Nicoletti, Ferdinando; Brunello, Nicoletta; Drago, Filippo; Sortino, Maria Angela; Copani, Agata

    2016-01-01

    Selective reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, increase circulating Transforming-Growth-Factor-β1 (TGF-β1) levels in depressed patients, and are currently studied for their neuroprotective properties in Alzheimer's disease. TGF-β1 is an anti-inflammatory cytokine that exerts neuroprotective effects against β-amyloid (Aβ)-induced neurodegeneration. In the present work, the SSRI, fluoxetine, was tested for the ability to protect cortical neurons against 1 μM oligomeric Aβ1-42-induced toxicity. At therapeutic concentrations (100 nM-1 μM), fluoxetine significantly prevented Aβ-induced toxicity in mixed glia-neuronal cultures, but not in pure neuronal cultures. Though to a lesser extent, also sertraline was neuroprotective in mixed cultures, whereas serotonin (10 nM-10 μM) did not mimick fluoxetine effects. Glia-conditioned medium collected from astrocytes challenged with fluoxetine protected pure cortical neurons against Aβ toxicity. The effect was lost in the presence of a neutralizing antibody against TGF-β1 in the conditioned medium, or when the specific inhibitor of type-1 TGF-β1 receptor, SB431542, was added to pure neuronal cultures. Accordingly, a 24 h treatment of cortical astrocytes with fluoxetine promoted the release of active TGF-β1 in the culture media through the conversion of latent TGF-β1 to mature TGF-β1. Unlike fluoxetine, both serotonin and sertraline did not stimulate the astrocyte release of active TGF-β1. We conclude that fluoxetine is neuroprotective against Aβ toxicity via a paracrine signaling mediated by TGF-β1, which does not result from a simplistic SERT blockade.

  14. Differentiation syndrome in acute myeloid leukemia after treatment with azacitidine.

    PubMed

    Laufer, Christin B; Roberts, Owen

    2015-11-01

    We report a case report of hyperleukocytosis, fever, hypotension, pulmonary and pericardial effusions, and acute kidney injury during initial treatment with azacitidine in a patient with AML-MRC. Collectively, the symptomatology resembled differentiation syndrome. Azacitidine has been previously associated with fever, peripheral edema, and hyperleukocytosis, but its side effect profile has never been described as similar to differentiation syndrome. The patient's deteriorating course quickly turned around after treatment with dexamethasone. This potential reaction, and potential treatment, is important for clinicians to be aware of.

  15. Re-evaluating the treatment of acute optic neuritis

    PubMed Central

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-01-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  16. Effects of pharmaceuticals on aquatic invertebrates. Part II: the antidepressant drug fluoxetine.

    PubMed

    Nentwig, Gerrit

    2007-02-01

    Fluoxetine, a selective serotonin reuptake inhibitor antidepressant and high-prescription-volume drug, is excreted unchanged or as a glucuronide from the human organism. Little is known about its fate in sewage treatment plants. Effects of fluoxetine on life-cycle parameters of the midge Chironomus riparius, especially development (mean emergence time), emergence, sex ratio, and fecundity, were assessed, as well as effects on reproduction of the oligochaete Lumbriculus variegatus and of the freshwater mudsnail Potamopyrgus antipodarum. Due to the moderate lipophilic properties of the compound with a log P (OW) of 4.05, C. riparius and L. variegatus were exposed to fluoxetine via spiked artificial sediment at a nominal concentration range between 0.15 and 5.86 mg/kg (dry weight). Additionally, a test was performed exposing P. antipodarum via water in a nominal concentration range between 0.64 and 400 mug/L. As endpoints, emergence rate and timing, sex ratio, clutch numbers and clutch size of the midges, the number of worms in the oligochaete test, as well as the number of embryos in the snail test were monitored. For C. riparius, no clear substance-related effects were observed; for L. variegatus, the results indicated a slight increase in reproduction, which was statistically significant at nominal fluoxetine concentrations of 0.94 and 2.34 mg/kg. In P. antipodarum, the antidepressant reduced reproduction significantly. No observed effect concentration (NOEC) and 10% effect concentration (EC(10)) were determined to be 0.47 and 0.81 mug/L, respectively, based on measured fluoxetine concentrations in water. These low values indicate that P. antipodarum and possibly other aquatic mollusks are sensitive to fluoxetine and that the drug might pose a risk to gastropod populations in the field.

  17. Ecotoxicological assessments show sucralose and fluoxetine affect the aquatic plant, Lemna minor.

    PubMed

    Amy-Sagers, Cherisse; Reinhardt, Keith; Larson, Danelle M

    2017-04-01

    Pharmaceuticals and personal care products (PPCP) are prevalent in aquatic systems, yet the fate and impacts on aquatic plants needs quantification for many compounds. We measured and detected sucralose (an artificial sweetener), fluoxetine (an antidepressant), and other PPCP in the Portneuf River in Idaho, USA, where Lemna minor (an aquatic plant in the environment and used in ecotoxicology studies) naturally occurs. Sucralose was hypothesized to negatively affect photosynthesis and growth of L. minor because sucralose is a chlorinated molecule that may be toxic or unusable for plant metabolism. A priori hypotheses were not created for fluoxetine due to lack of previous studies examining its impacts on plants. We conducted laboratory ecotoxicological assessments for a large range of concentrations of sucralose and fluoxetine on L. minor physiology and photosynthetic function. Frond green leaf area, root length, growth rate, photosynthetic capacity, and plant carbon isotopic composition (discrimination relative to a standard; δ(13)C) were measured among treatments ranging from 0 to 15000nmol/L-sucralose and 0-323nmol/L-fluoxetine. Contrary to our predictions, sucralose significantly increased green leaf area, photosynthetic capacity, and δ (13)C of L. minor at environmentally relevant concentrations. The increase of δ (13)C from sucralose amendments and an isotope-mixing model indicated substantial sucralose uptake and assimilation within the plant. Unlike humans who cannot break down and utilize sucralose, we documented that L. minor-a mixotrophic plant-can use sucralose as a sugar substitute to increase its green leaf area and photosynthetic capacity. Fluoxetine significantly decreased L. minor root growth, daily growth rate, and asexual reproduction at 323nmol/L-fluoxetine; however, ambiguity remains regarding the mechanisms responsible and the applicability of these extreme concentrations unprecedented in the natural environment. To our knowledge, this was

  18. A strategic plan to accelerate development of acute stroke treatments.

    PubMed

    Marler, John R

    2012-09-01

    In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care.

  19. Treatment of acute abscesses in the casualty department.

    PubMed Central

    Simms, M H; Curran, F; Johnson, R A; Oates, J; Givel, J C; Chabloz, R; ALexander-Williams, J

    1982-01-01

    In the treatment of acute pyogenic soft-tissue abscess incision, curettage, and primary suture was compared with incision and drainage alone in a randomised prospective trial. Operations were performed under antibiotic cover by casualty officers, and patients were reviewed by an independent observer in a septic dressing clinic. Altogether 114 patients were studied, of whom 54 were treated by curettage and primary suture and 60 by simple drainage. The mean healing time was 8.9 days in those treated by primary suture and 7.8 days in those treated by simple drainage (p less than 0.05). Primary healing failed to occur in 19 (35%) of the sutured wounds, but there were no other complications in either group. It is concluded that incision and drainage alone is adequate treatment for acute soft-tissue abscess. PMID:6805714

  20. Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: protocol for a network meta-analysis

    PubMed Central

    Salanti, Georgia; Atkinson, Lauren Z; Leucht, Stefan; Ruhe, Henricus G; Turner, Erick H; Chaimani, Anna; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Imai, Hissei; Shinohara, Kiyomi; Suganuma, Aya; Watanabe, Norio; Stockton, Sarah; Geddes, John R

    2016-01-01

    Introduction Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression. Methods and analysis We will include all randomised controlled trials reported as double-blind and comparing one active drug with another or with placebo in the acute phase treatment of major depression in adults. We are interested in comparing the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will be the proportion of patients who responded to or dropped out of the allocated treatment. Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. To rank the various treatments for each outcome, we will use the surface under the cumulative ranking curve and the mean ranks. We will employ local as well as global methods to evaluate consistency. We will fit our model in a Bayesian framework using OpenBUGS, and produce results and various checks in Stata and R. We will also assess the quality of evidence contributing to network

  1. Hydrocortisone treatment of early SIRS in acute experimental pancreatitis.

    PubMed

    Gloor, B; Uhl, W; Tcholakov, O; Roggo, A; Muller, C A; Worni, M; Büchler, M W

    2001-10-01

    This work studied the effects of hydrocortisone treatment in experimental acute pancreatitis on cytokines, phospholipase A2, and breakdown products of arachidonic acid and survival. Edematous and necrotizing pancreatitis were induced in Wistar rats by cerulein hyperstimulation and retrograde intraductal infusion of sodium taurocholate, respectively. Hydrocortisone (10 mg/kg) was administered intravenously 10 minutes after induction of acute pancreatitis. Serum was assayed for phospholipase A2; interleukin (IL) 1beta, IL-6, IL-10, thromboxane B2; Prostaglandin E2; and leukotriene B4 at five different time points. A significant release of inflammatory mediators was seen only in the severe model. Hydrocortisone powerfully suppressed arachidonic acid breakdown products and only mildly attenuated the systemic increase of phospholipase A2 and pro- and antiinflammatory cytokines. The mortality rate after 72 hr in the severe model was 86%. Hydrocortisone treatment reduced mortality to 13% (P = 0.001; Fisher's exact test). Hydrocortisone seems to be effective in the treatment of the early systemic inflammatory response syndrome associated with severe acute pancreatitis.

  2. Selecting initial treatment of acute myeloid leukaemia in older adults.

    PubMed

    Podoltsev, Nikolai A; Stahl, Maximilian; Zeidan, Amer M; Gore, Steven D

    2016-10-08

    More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of <1year. Selecting initial treatment for these patients involves an assessment of 'fitness' for induction chemotherapy. This is done based on patient and disease-related characteristics which help to estimate treatment-related mortality and chance of complete remission with induction chemotherapy. If the risk of treatment-related mortality is high and/or the likelihood of a patient achieving a complete remission is low, lower-intensity treatment (low-dose cytarabine, decitabine and azacitidine) should be discussed. As outcomes in both groups of patients remain poor, enrolment into clinical trials of novel agents with varying mechanisms of action should be considered for all older adults with AML. Novel agents in Phase III development include CPX-351, guadecitabine (SGI-110), quizartinib, crenolanib, sapacitabine, vosaroxin and volasertib.

  3. 21 CFR 520.980 - Fluoxetine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Fluoxetine. 520.980 Section 520.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... conjunction with a behavior modification plan. (3) Limitations. Federal law restricts this drug to use by...

  4. 21 CFR 520.980 - Fluoxetine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fluoxetine. 520.980 Section 520.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... conjunction with a behavior modification plan. (3) Limitations. Federal law restricts this drug to use by...

  5. Filgrastim for the treatment of hematopoietic acute radiation syndrome.

    PubMed

    Farese, A M; MacVittie, T J

    2015-09-01

    The U.S. Food and Drug Administration (FDA) recently approved Neupogen(®) (filgrastim) for the treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident. It is the first medical countermeasure currently approved by the FDA for this indication under the criteria of the FDA "animal rule". This article summarizes the consequences of high-dose radiation exposure, a description of the hematopoietic acute radiation syndrome (H-ARS), the use of hematopoietic growth factors in radiation accident victims and current available treatments for H-ARS with an emphasis on the use of Neupogen in this scenario.

  6. Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.; Levy, Michael

    2016-01-01

    Opinion statement Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that primarily attacks the optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 water channel on astrocytes. With wider recognition of NMOSD, a standard of care for treatment of this condition has condition based on a growing series of retrospective and prospective studies. This review covers the present state of the field in the treatment of acute relapses, preventive approaches, and therapies for symptoms of NMOSD. PMID:26705758

  7. Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice

    PubMed Central

    Marlatt, Michael W.; Lucassen, Paul J.; van Praag, Henriette

    2010-01-01

    Hippocampal neurogenesis can be regulated by extrinsic factors, such as exercise and antidepressants. While there is evidence that the serotonin re-uptake inhibitor (SSRI) fluoxetine (Prozac) enhances neurogenesis, the new dual serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine has not been evaluated in this context. In addition, it is unclear whether effects of antidepressants and running on cell genesis and behavior are of similar magnitude in mice. Here,we assessed neurogenesis and open field behavior in 2 month old female C57Bl/6 mice after 28 days of treatment with either fluoxetine (18 mg/kg), duloxetine (2, 6 or 18 mg/kg) or exercise. New cell survival, as measured by 5-bromo-2´-deoxyuridine (BrdU) labeled cells, was enhanced by 200% in the running group only. Both running and fluoxetine, but not duloxetine, increased the percentage of new cells that became neurons. In the open field test, animals treated with either drug spent less time in the center than controls and runners. In addition, fluoxetine treatment resulted in reduced locomotor activity. Together, these data not only show that the neurogenic response to exercise is much stronger than to antidepressants, but also imply a low likelihood that reported effects of these two drugs on anxiety are mediated by adult neurogenesis in C57Bl/6 mice. PMID:20381469

  8. Treatment of Acute Lymphoblastic Leukemia from Traditional Chinese Medicine

    PubMed Central

    Huang, Hung-Jin; Kuo, Chia-Chen; Chen, Calvin Yu-Chian

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX) is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs) inhibit the thymidylate synthase (TS). Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM) as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment. PMID:25136372

  9. Evaluating conservative treatment for acute appendicitis with lump formation

    PubMed Central

    Malik, Ajaz Ahmad; Wani, Mohd Lateef; Wani, Shadab Nabi; Parray, Fazl Qadir; Nayeem-Ul-Hassan; Irshad, Ifat

    2012-01-01

    Background: Interval appendectomy after acute appendicitis with lump formation (phlegmon) remains controversial. We conducted this study to determine the risk of recurrent appendicitis following initial non-operative treatment for appendicitis, and evaluate factors associated with recurrence. Secondarily, we evaluate the efficacy of interval appendectomy versus no appendectomy. Materials and Methods: Patients who received conservative treatment for appendicitis with lump formation were prospectively studied from June 2006 to June 2008. These patients were followed for recurrence of appendicitis. Results: Of 763 patients with acute appendicitis some 220 patients had lump formation (28.8%). Median age was 28 years. Conservative treatment was successful in 213 (96.8%) patients. The rate of recurrence was 13.1%, all occurring within six months after the index admission. Mean follow-up was 26±18 months. Conclusion: Conservative treatment of appendicitis with lump formation is efficient and the recurrence rate is low. Routine interval appendectomy after initial conservative treatment for lump formation is not a cost-effective intervention and not recommended. PMID:22416152

  10. System of acute medical support to emergency during dental treatment.

    PubMed

    Kawahara, M; Takeshita, T; Akita, S

    1986-01-01

    The Resuscitation Committee of Hiroshima City Dental Association was established in 1983 in order to provide acute medical support in case of emergency during dental treatment at private dental clinics. This Committee is composed of representatives from the Hiroshima City Dental Association, Hiroshima University School of Dentistry, Hiroshima University School of Medicine, Hiroshima City Health Bureau, and Hiroshima City Fire and Ambulance Department. A portable ECG monitor with defibrillator and a resuscitation kit are held in readiness at the Hiroshima University Hospital. In case of emergency during dental treatment at a private dental clinic, we hurry to the clinic with the resuscitation set and give emergency treatment. We have been involved in two cases of emergency since this system started. Both of them recovered without any sequelae. Besides these activities, we give lectures annually to dentists and dental hygienists on the treatment of medical emergencies.

  11. Biopsy proven acute interstitial nephritis after treatment with moxifloxacin

    PubMed Central

    2010-01-01

    Background Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillines and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones. Case Presentation Here we describe a case of biopsy proven interstitial nephritis after moxifloxacin treatment. The patient presented with fever, rigors and dialysis dependent acute kidney injury, just a few days after treatment of a respiratory tract infection with moxifloxacin. The renal biopsy revealed dense infiltrates mainly composed of eosinophils and severe interstitial edema. A course of oral prednisolone (1 mg/kg/day) was commenced and rapidly tapered to zero within three weeks. The renal function improved, and the patient was discharged with a creatinine of 107 μmol/l. Conclusion This case illustrates that pharmacovigilance is important to early detect rare side effects, such as AIN, even in drugs with a favourable risk/benefit ratio such as moxifloxacin. PMID:20731847

  12. Treatment of Orbital Complications Following Acute Rhinosinusitis in Children

    PubMed Central

    Wan, Yuzhu; Shi, Guanggang; Wang, Haibo

    2016-01-01

    Background: The orbital complications account for about 80% of all complications secondary to acute rhinosinusitis. If the treatment is not correct and in time, orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications. Aims: To evaluate the therapeutic efficacy of conservative therapy for the patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in children. Study Design: Retrospective cross-sectional study. Methods: The retrospective study included 31 pediatric patients with orbital complications secondary to acute rhinosinusitis. In all cases, intensive treatment was initiated with a combination of oral or intravenous antibiotics, glucocorticoid and gelomyrtol forte after admission. ESS was performed if an improvement in the condition of patients did not occur after 48 hours. However, the patients with orbital SPA, motility disorders of eyeball or decreased vision received ESS immediately within 24 hours. Results: Sixteen patients were cured by conservative therapy and 15 patients by ESS. All of the signs and symptoms disappeared after conservative therapy or ESS. There were no recurrences within the follow-up period of 1 to 8 years. Conclusion: Conservative therapy is an effective method for patients with inflammatory edema and most cases of orbital cellulitis in children. SPA can be cured by ESS. PMID:27606135

  13. Treatment of acute erythroleukemia with Azacitidine: A case series

    PubMed Central

    Pierdomenico, Francesca; Almeida, Antonio

    2013-01-01

    Acute erythroleukemia (AEL) is a rare form of acute myeloid leukemia (AML) often associated with a poor prognosis. It is more frequent in elderly patients, limiting the use aggressive therapies. Azacitidine is a hypomethylating agent with recognized efficacy in high risk myelodysplasia and AML in the elderly. Here we report 5 cases of AEL treated with Azacitidine. The cohort included 4 men and 1 woman, median age 70. One patient had been refractory to intensive chemotherapy, the others received Azacitidine as first line. Treatment was well tolerated. Four patients achieved transfusion independence. Two patients achieved complete remission and 1 achieved partial remission. After a median follow up time of 20 months, the median survival of the cohort was 20 months. Three patients died of disease progression. These results confirm the therapeutic value of Azacitidine in AEL. PMID:24371777

  14. Acute pancreatitis in ICU secondary to treatment with tigecycline.

    PubMed

    Bernas Albeniz, A; Aveiga Valencia, D A; Etxeberria Zabala, L; Zaldibar-Gerrikagoitia Bilbao, J; Aguilera Celorrio, L

    2017-01-01

    Tigecycline is a broad spectrum antimicrobial agent, structurally similar to minocycline and that shares some tetracycline-related side effects. A case report is presented on a 68-year-old female who received tigecycline for a sepsis of unknown origin and who, in the following 5days, developed abdominal pain and elevated pancreatic enzymes, which suggested acute pancreatitis. After ruling out other origins, and according to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of the acute pancreatitis, a complication that has been reported 5 times in the database of the Spanish pharmacosurveillance system since 2009. Close monitoring of abdominal signs and symptoms is recommended during treatment with tigecycline, since adverse effects affecting the digestive system are the most prevalent ones when using this drug.

  15. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus.

    PubMed

    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission.

  16. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

    PubMed Central

    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

  17. EFFECT OF FLUOXETINE AND BROMOCRIPTINE ON CRAVING OCCURRING DURING WITHDRAWAL FROM ALCOHOL

    PubMed Central

    Chatterjee, Sudipto; Isaac, Mohan K.

    1996-01-01

    Craving is an integral element in the understanding of alcohol dependence. Recent human and animal research implicates the serotonergic and dopaminergic systems in the mediation of excessive alcohol consumption. In this study, a cue-based approach was used to qualify and quantify craving occurring during acute withdrawal from alcohol. Fifty alcoholics were given either placebo, bromocriptine or fluoxetine in a randomised double-blind fashion and craving was sequentially measured over the next 15 days. Both fluoxetine and bromocriptine significantly attenuated total craving scores without similarly affecting withdrawal symptoms. The results suggest the importance of neurotransmitters in mediating craving. The significance of these data in the light of various behavioural and neurochemical models have been discussed. PMID:21584128

  18. Impact of excipients in the chronic toxicity of fluoxetine on the alga Chlorella vulgaris.

    PubMed

    Silva, Aurora; Santos, Lúcia H M L M; Delerue-Matos, Cristina; Figueiredo, Sónia A

    2014-01-01

    Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) widely used in the treatment of major depression. It has been detected in surface and wastewaters, being able to negatively affect aquatic organisms. Most of the ecotoxicity studies focused only in pharmaceuticals, though excipients can also pose a risk to non-target organisms. In this work the ecotoxicity of five medicines (three generic formulations and two brand labels) containing the same active substance (fluoxetine hydrochloride) was tested on the alga Chlorella vulgaris, in order to evaluate if excipients can influence their ecotoxicity. Effective concentrations that cause 50% of inhibition (EC50) ranging from 0.25 to 15 mg L⁻¹ were obtained in the growth inhibition test performed for the different medicines. The corresponding values for fluoxetine concentration are 10 times lower. Higher EC50 values had been published for the same alga considering only the toxicity of fluoxetine. Therefore, this increase in toxicity may be attributed to the presence of excipients. Thus more studies on ecotoxicological effects of excipients are required in order to assess the environmental risk they may pose to aquatic organisms.

  19. Effects of lobeline and reboxetine, fluoxetine, or bupropion combination on depression-like behaviors in mice.

    PubMed

    Roni, Monzurul Amin; Rahman, Shafiqur

    2015-12-01

    Evidence suggests that lobeline, a nicotinic acetylcholine receptor ligand, has antidepressant-like properties in mice. The present study investigated the possible additive or synergistic effects of lobeline in combination with commonly used antidepressants, such as reboxetine, fluoxetine, or bupropion, using the tail suspension test (TST) and the forced swim test (FST) in C57BL/6J mice. Reboxetine (5 or 10 mg/kg, i.p.), fluoxetine (5 or 10 mg/kg, i.p.), or bupropion (2 or 4 mg/kg, i.p.) were administered 30 min before TST or FST. A fixed dose of lobeline (1 mg/kg, i.p.) was injected 15 min prior to tests. Co-administration of lobeline and reboxetine, fluoxetine, or bupropion significantly reduced immobility time in the TST and FST in comparison to the antidepressants used alone. The results suggest that lobeline enhanced the effects of reboxetine, fluoxetine, or bupropion in mice. Therefore, lobeline or similar nicotinic receptor ligand may have therapeutic potential as an adjunct for the treatment of major depression.

  20. Changes in prescription habits with the introduction of generic fluoxetine.

    PubMed

    McLay, Robert; Klinski, Angelica

    2008-01-01

    When the patent on fluoxetine expired in 2001, prices for it fell sharply and marketing decreased. We investigated how market share for fluoxetine changed with the introduction of the generic. Prescribing information was tracked at a military hospital where providers knew the cost of medication, but were not compelled to use the cheaper form. Market share for fluoxetine among selective serotonin reuptake inhibitors was observed for the 64 months surrounding the introduction, and changes were examined by linear regression analysis. Results showed that in the 32 months before the introduction of the generic, fluoxetine maintained a relatively steady share of prescriptions. After the introduction of the generic, fluoxetine steadily lost market share over time. No significant relationship could be seen between drug company visits and gains for their individual products. Examination of all Department of Defense prescriptions for the 16 months surrounding the introduction of generic fluoxetine showed a similar drop in its market share.

  1. Fluoxetine induces input-specific hippocampal dendritic spine remodeling along the septo-temporal axis in adulthood and middle age

    PubMed Central

    McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar

    2015-01-01

    Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce structural rearrangements and changes in synaptic transmission in hippocampal circuitry. In the adult hippocampus, structural changes include neurogenesis, dendritic and axonal plasticity of pyramidal and dentate granule neurons, and dedifferentiation of dentate granule neurons. However, much less is known about how chronic fluoxetine affects these processes along the septo-temporal axis and during the aging process. Importantly, studies documenting the effects of fluoxetine on density and distribution of spines along different dendritic segments of dentate granule neurons and CA1 pyramidal neurons along the septo-temporal axis of hippocampus in adulthood and during aging are conspicuously absent. Here, we use a transgenic mouse line in which mature dentate granule neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent protein (GFP) to investigate the effects of chronic fluoxetine treatment (18mg/kg/day) on input-specific spine remodeling and mossy fiber structural plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In addition, we examine levels of adult hippocampal neurogenesis, maturation state of dentate granule neurons, neuronal activity and glutamic acid decarboxylase-67 expression in response to chronic fluoxetine in adulthood and middle age. Our studies reveal that while chronic fluoxetine fails to augment adult hippocampal neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input-specific synaptic remodeling than the hippocampus in adulthood with the stratum-oriens of CA1 exhibiting heightened structural plasticity. The input-specific changes and circuit

  2. Fluoxetine induces input-specific hippocampal dendritic spine remodeling along the septotemporal axis in adulthood and middle age.

    PubMed

    McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar

    2015-11-01

    Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce structural rearrangements and changes in synaptic transmission in hippocampal circuitry. In the adult hippocampus, structural changes include neurogenesis, dendritic, and axonal plasticity of pyramidal and dentate granule neurons, and dedifferentiation of dentate granule neurons. However, much less is known about how chronic fluoxetine affects these processes along the septotemporal axis and during the aging process. Importantly, studies documenting the effects of fluoxetine on density and distribution of spines along different dendritic segments of dentate granule neurons and CA1 pyramidal neurons along the septotemporal axis of hippocampus in adulthood and during aging are conspicuously absent. Here, we use a transgenic mouse line in which mature dentate granule neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent protein (GFP) to investigate the effects of chronic fluoxetine treatment (18 mg/kg/day) on input-specific spine remodeling and mossy fiber structural plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In addition, we examine levels of adult hippocampal neurogenesis, maturation state of dentate granule neurons, neuronal activity, and glutamic acid decarboxylase-67 expression in response to chronic fluoxetine in adulthood and middle age. Our studies reveal that while chronic fluoxetine fails to augment adult hippocampal neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input-specific synaptic remodeling than the hippocampus in adulthood with the stratum-oriens of CA1 exhibiting heightened structural plasticity. The input-specific changes and circuit

  3. Fluoxetine stimulates anti-inflammatory IL-10 cytokine production and attenuates sensory deficits in a rat model of decompression sickness.

    PubMed

    Blatteau, Jean-Eric; de Maistre, Sébastien; Lambrechts, Kate; Abraini, Jacques; Risso, Jean-Jacques; Vallée, Nicolas

    2015-12-15

    Despite "gold standard" hyperbaric oxygen treatment, 30% of patients suffering from neurological decompression sickness still exhibit incomplete recovery, including sensory impairments. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory effects in the setting of cerebral ischemia. In this study, we focused on the assessment of sensory neurological deficits and measurement of circulating cytokines after decompression in rats treated or not with fluoxetine. Seventy-eight rats were divided into a clinical (n = 38) and a cytokine (n = 40) group. In both groups, the rats were treated with fluoxetine (30 mg/kg po, 6 h beforehand) or with a saccharine solution. All of the rats were exposed to 90 m seawater for 45 min before staged decompression. In the clinical group, paw withdrawal force after mechanical stimulation and paw withdrawal latency after thermal stimulation were evaluated before and 1 and 48 h after surfacing. At 48 h, a dynamic weight-bearing device was used to assess postural stability, depending on the time spent on three or four paws. For cytokine analysis, blood samples were collected from the vena cava 1 h after surfacing. Paw withdrawal force and latency were increased after surfacing in the controls, but not in the fluoxetine group. Dynamic weight-bearing assessment highlighted a better stability on three paws for the fluoxetine group. IL-10 levels were significantly decreased after decompression in the controls, but maintained at baseline level with fluoxetine. This study suggests that fluoxetine has a beneficial effect on sensory neurological recovery. We hypothesize that the observed effect is mediated through maintained anti-inflammatory cytokine IL-10 production.

  4. Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers.

    PubMed

    DeVane, C Lindsay; Donovan, Jennifer L; Liston, Heidi L; Markowitz, John S; Cheng, Kenneth T; Risch, S Craig; Willard, Lauren

    2004-02-01

    An antidepressant for use in the patient receiving concomitant drug treatment, over-the-counter medications, or herbal products should lack cytochrome P-450 (CYP) 3A4 inductive or inhibitory activity to provide the least likelihood of a drug-drug interaction. This study addresses the potential of 4 diverse antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit or induce CYP3A4. In a 4-way crossover design, 16 subjects received clinically relevant doses of venlafaxine, nefazodone, or sertraline for 8 days or fluoxetine for 11 days. Treatments were separated by a 7- to 14-day washout period and fluoxetine was always the last antidepressant taken. CYP3A4 activity was evaluated for each subject at baseline and following each antidepressant using the erythromycin breath test (EBT) and by the pharmacokinetics of alprazolam (ALPZ) after 2-mg dose of oral ALPZ. Compared to baseline, venlafaxine, sertraline, and fluoxetine caused no apparent inhibition or induction of erythromycin metabolism (P > 0.05). For nefazodone, a statistically significant inhibition was observed (P < 0.0005). Nefazodone was also the only antidepressant that caused a significant change in ALPZ disposition, decreasing its area under the concentration-versus-time curve (AUC; P < 0.01), and increasing its elimination half-life (16.4 vs. 12.3 hours; P < 0.05) compared with values at baseline. No significant differences were found in the pharmacokinetics of ALPZ with any of the other antidepressants tested. These results demonstrate in vivo that, unlike nefazodone, venlafaxine, sertraline, and fluoxetine do not possess significant metabolic inductive or inhibitory effects on CYP3A4.

  5. Effects of fluoxetine on protein expression of potassium ion channels in the brain of chronic mild stress rats

    PubMed Central

    Chen, Chunlin; Wang, Ling; Rong, Xianfang; Wang, Weiping; Wang, Xiaoliang

    2014-01-01

    The purpose of this study is to investigate the expression of major potassium channel subtypes in the brain of chronical mild stress (CMS) rats and reveal the effects of fluoxetine on the expression of these channels. Rats were exposed to a variety of unpredictable stress for three weeks and induced anhedonia, lower sucrose preference, locomotor activity and lower body weight. The protein expressions were determined by Western blot. CMS significantly increased the expression of Kv2.1 channel in frontal cortex but not in hippocampus, and the expression level was normalized after fluoxetine treatment. The expression of TREK-1 channel was also obviously increased in frontal cortex in CMS rats. Fluoxetine treatment might prevent this increase. However, the expression of Kv3.1 and Kv4.2 channels was considerably decreased in hippocampus after CMS, and was not affected by fluoxetine. These results suggest that different subtypes of potassium channels are associated with the pathophysiology of depression and that the therapeutical effects of fluoxetine may relate to Kv2.1 and TREK-1 potassium channels. PMID:26579425

  6. Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine.

    PubMed

    Gürbüz Özgür, Börte; Aksu, Hatice; Birincioğlu, Mustafa; Dost, Turhan

    2015-11-01

    Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10mg/kg fluoxetine, 50mg/kg allopurinol, 50mg/kg allopurinol+10 mg/kg fluoxetine; n=8 per group), and forced swimming tests were performed before and after 14days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy.

  7. [Immunotherapy for the treatment of acute appendicitis in children].

    PubMed

    Bulanova, A A; Akhanzaripov, Z A

    1994-08-01

    The immune status was studied during the development of the disease in 182 children who were operated on for acute appendicitis. T lymphocytes and their subpopulations circulating in the blood, as well as B lymphocytes, immunoglobulins A, M, G, and immune complexes were determined. The character of changes of these values before the operation and in various postoperative periods were determined. The effect of complex treatment, including T-activin, on the clinical and immunological parameters in children with acute appendicitis was appraised. Analysis of the results showed that a transitory immunodepressive state forms in children with the disease, which is more marked in the destructive form, with normalization of the main values of cell-mediated and humoral immunity by the 7th day after appendectomy. In a complicated course of acute appendicitis the state of immunodeficiency is torpid in character and does not return to normal values even after clinical recovery, i.e. before discharge from the clinic. Inclusion of the immunostimulating agent T-activin into the complex treatment of patients with appendicitis ensures a more rapid involution of the main clinical manifestations of the disease. The therapeutic effect was most pronounced in destructive appendicitis: after 3 days of treatment the pain syndrome was encountered twice less frequently and intestinal paresis more than twice less frequently in these patients, and the term of hospital stay (8.8 +/- 0.4 days) was less shorter than for children of the control group (12.2 +/- 1.9 days) who did not receive T-activin in the therapeutic complex.

  8. Pathophysiology and Surgical Treatment of Type A Acute Aortic Dissection

    PubMed Central

    Karube, Norihisa; Yasuda, Shota; Miyamoto, Takuma; Matsuki, Yusuke; Isoda, Susumu; Goda, Motohiko; Suzuki, Shinichi; Masuda, Munetaka; Imoto, Kiyotaka

    2016-01-01

    Objectives: We report the pathophysiology and treatment results of type A acute aortic dissection from our 20-year experience. Methods: We studied 673 patients with type A acute aortic dissection who underwent initial treatment from 1994 through July 2014. We divided these patients into two groups. The former group comprised 448 patients from 1994 through 2008, and the latter group comprised 225 patients from 2009 onward, when the current strategy of initial treatment and surgical technique including the early organ reperfusion therapies were established. Results: Women were significantly often presented than men in patients over 60 years of age. Thrombosed-type dissection accounted for more than half in patients over 70 years, and significantly often complicated pericardial effusion and cardiac tamponade than patent type. Malperfusion occurred in 26% of patients. Central repair operations were performed in 579 patients. In-hospital mortality for all patients was 15%, and for the patients who underwent central repair operations was 10%. Former period of operation, malperfusion, and preoperative cardiopulmonary arrest were significant risk factor of in-hospital death. Preoperative left main trunk (LMT) stents were placed in eight patients and superior mesenteric artery (SMA) intervention was performed in five, they were effective to improve the outcome. From 2009 onward, in-hospital mortality was 5.0% and there was no significant risk factor. Conclusion: Surgical results of type A acute aortic dissection were dramatically improved in the past 20 years. Early reperfusion strategy for the patients with malperfusion improved the outcomes. (This article is a translation of Jpn J Vasc Surg 2015; 24: 127–134.) PMID:27738456

  9. WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis.

    PubMed

    Di Saverio, Salomone; Birindelli, Arianna; Kelly, Micheal D; Catena, Fausto; Weber, Dieter G; Sartelli, Massimo; Sugrue, Michael; De Moya, Mark; Gomes, Carlos Augusto; Bhangu, Aneel; Agresta, Ferdinando; Moore, Ernest E; Soreide, Kjetil; Griffiths, Ewen; De Castro, Steve; Kashuk, Jeffry; Kluger, Yoram; Leppaniemi, Ari; Ansaloni, Luca; Andersson, Manne; Coccolini, Federico; Coimbra, Raul; Gurusamy, Kurinchi S; Campanile, Fabio Cesare; Biffl, Walter; Chiara, Osvaldo; Moore, Fred; Peitzman, Andrew B; Fraga, Gustavo P; Costa, David; Maier, Ronald V; Rizoli, Sandro; Balogh, Zsolt J; Bendinelli, Cino; Cirocchi, Roberto; Tonini, Valeria; Piccinini, Alice; Tugnoli, Gregorio; Jovine, Elio; Persiani, Roberto; Biondi, Antonio; Scalea, Thomas; Stahel, Philip; Ivatury, Rao; Velmahos, George; Andersson, Roland

    2016-01-01

    Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.

  10. [Acute kidney injury and septic shock: experiences in treatment].

    PubMed

    Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco

    2012-01-01

    Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

  11. Morphine in the treatment of acute pulmonary oedema--Why?

    PubMed

    Ellingsrud, C; Agewall, S

    2016-01-01

    Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords "pulmonary oedema" OR "lung oedema" OR "acute heart failure" AND "morphine" was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52-5.18, p<0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors. Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect--and especially the risk--when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.

  12. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  13. [The efficacy of the acute pancreatitis' surgical treatment].

    PubMed

    Ostrovskiĭ, V K; Rodionov, P N; Makarov, S V

    2012-01-01

    The comparative analysis of blood levels of leukocytes, lymphocytes, the leukocytic intoxication index, amylase, lipase, lactatdehydrogenase and creatinphosphokinase, measured in operated patients with the acute pancreatitis, demonstrated the general positive dynamics of the patients condition. The higher blood levels of the substances in died patients demonstrate the important prognostic value of them. The higher levels of amylase, lipase, lactatdehydrogenase and creatinphosphokinase by the end of the clinical treatment together with the normalization of the rest laboratory data may witness the higher risk of the chronisation of the pancreatitis.

  14. Diagnosis and treatment of acute low back pain.

    PubMed

    Casazza, Brian A

    2012-02-15

    Acute low back pain is one of the most common reasons for adults to see a family physician. Although most patients recover quickly with minimal treatment, proper evaluation is imperative to identify rare cases of serious underlying pathology. Certain red flags should prompt aggressive treatment or referral to a spine specialist, whereas others are less concerning. Serious red flags include significant trauma related to age (i.e., injury related to a fall from a height or motor vehicle crash in a young patient, or from a minor fall or heavy lifting in a patient with osteoporosis or possible osteoporosis), major or progressive motor or sensory deficit, new-onset bowel or bladder incontinence or urinary retention, loss of anal sphincter tone, saddle anesthesia, history of cancer metastatic to bone, and suspected spinal infection. Without clinical signs of serious pathology, diagnostic imaging and laboratory testing often are not required. Although there are numerous treatments for nonspecific acute low back pain, most have little evidence of benefit. Patient education and medications such as nonsteroidal anti-inflammatory drugs, acetaminophen, and muscle relaxants are beneficial. Bed rest should be avoided if possible. Exercises directed by a physical therapist, such as the McKenzie method and spine stabilization exercises, may decrease recurrent pain and need for health care services. Spinal manipulation and chiropractic techniques are no more effective than established medical treatments, and adding them to established treatments does not improve outcomes. No substantial benefit has been shown with oral steroids, acupuncture, massage, traction, lumbar supports, or regular exercise programs.

  15. Estradiol accelerates the effects of fluoxetine on serotonin 1A receptor signaling.

    PubMed

    Li, Qian; Sullivan, Nicole R; McAllister, Carrie E; Van de Kar, Louis D; Muma, Nancy A

    2013-07-01

    A major problem with current anti-depressant therapy is that it takes on average 6-7 weeks for remission. Since desensitization of serotonin (5-HT)1A receptor signaling contributes to the anti-depressive response, acceleration of the desensitization may reduce this delay in response to antidepressants. The purpose of the present study was to test the hypothesis that estradiol accelerates fluoxetine-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus (PVN) of rats, via alterations in components of the 5-HT1A receptor signaling pathway. Ovariectomized rats were injected with estradiol and/or fluoxetine, then adrenocorticotropic hormone (ACTH) and oxytocin responses to a 5-HT1A receptor agonist (+)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) were examined to assess the function of 5-HT1A receptors in the PVN. Treatment with estradiol for either 2 or 7 days or fluoxetine for 2 days produced at most a partial desensitization of 5-HT1A receptor signaling, whereas 7 days of fluoxetine produced full desensitization. Combined treatment with estradiol and fluoxetine for 2 days produced nearly a full desensitization, demonstrating an accelerated response compared to either treatment alone. With two days of combined treatments, estradiol prevented the fluoxetine-induced increase in 5-HT1A receptor protein, which could contribute to the more rapid desensitization. Furthermore, EB treatment for 2 days decreased the abundance of the 35 kD Gαz protein which could contribute to the desensitization response. We found two isoforms of Gαz proteins with molecular mass of 35 and 33 kD, which differentially distributed in the detergent resistant microdomain (DRM) and in Triton X-100 soluble membrane region, respectively. The 35 kD Gαz proteins in the DRM can be sumoylated by SUMO1. Stimulation of 5-HT1A receptors with 8-OH-DPAT increases the sumoylation of Gαz proteins and reduces the 33 kD Gαz proteins, suggesting that these

  16. The Selective Serotonin Reuptake Inhibitor Fluoxetine Directly Inhibits Osteoblast Differentiation and Mineralization During Fracture Healing in Mice.

    PubMed

    Bradaschia-Correa, Vivian; Josephson, Anne M; Mehta, Devan; Mizrahi, Matthew; Neibart, Shane S; Liu, Chao; Kennedy, Oran D; Castillo, Alesha B; Egol, Kenneth A; Leucht, Philipp

    2016-11-21

    Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and μCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. © 2016 American Society for Bone and Mineral Research.

  17. Fosfomycin for the initial treatment of acute haematogenous osteomyelitis

    PubMed Central

    Corti, N; Sennhauser, F; Stauffer, U; Nadal, D

    2003-01-01

    Background and Aims: At our institution there has been a dichotomous antimicrobial treatment behaviour for acute haematogenous osteomyelitis (AHOM) since 1984. The surgical department favoured fosfomycin as initial choice and the medical department ß lactams. We aimed to compare the performance of both strategies. Methods: Data from patients discharged with the diagnosis of AHOM between January 1984 and January 1998 were gathered from the charts by means of a questionnaire. Patients receiving fosfomycin treatment (FT) were compared with those receiving fosfomycin plus other antimicrobials (FT+) and those receiving no fosfomycin treatment (NFT). Results: A total of 103 patients aged 0.1–15.5 years (mean 6.5, median 6.9) with AHOM received no surgical treatment initially. In 23 (22.3%) FT was instilled initially, in 47 (45.6%) FT+, and in 33 (32.0%) NFT. The pathogen was established in 30%, 36%, and 42% of FT, FT+, and NFT patients, respectively, Staphylococcus aureus being the predominant isolate. Mean C reactive protein levels and erythrocyte sedimentation rates normalised in all treatment groups after two and four weeks, respectively. The mean duration of intravenous antimicrobial treatment in FT patients was 2.5 weeks, in FT+ patients 3.1 weeks, and in NFT patients 3.8 weeks (p < 0.05), whereas the mean duration of intravenous plus oral treatment was comparable (7.1 v 6.8 v 6.5 weeks). Conclusions: The leucocyte penetrating fosfomycin performed similarly to extracellular ß lactams in the treatment of AHOM. Intravenous treatment for longer than 2.5 weeks offered no advantage. PMID:12765918

  18. The influence of microglia activation on the efficacy of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine in a rat model of neuropathic pain.

    PubMed

    Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-02-15

    The analgesic properties of antidepressants are often used in the treatment of neuropathy; however their influence on glial cells in maintaining neuropathic pain is unknown. Our studies examined the neuropathic pain-relieving properties after intraperitoneal injection of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine 7 days after sciatic nerve injury (CCI) in rats and its influence on microglia/macrophages (IBA-1) and astroglia (GFAP) activation in the spinal cord and dorsal root ganglia (DRG) using Western blot. All tested antidepressants significantly reduced CCI-induced allodynia but hyperalgesia was only antagonised by fluoxetine, doxepine and venlafaxine. The strongest analgesia was observed after fluoxetine administration. Western blot analysis showed the upregulation of the IBA-1 in the lumbar spinal cord and DRG after amitriptyline or milnacipran administration in CCI-exposed rats, whereas after fluoxetine the downregulation was observed. The administration of doxepin did not change the IBA-1 protein level in both studied structures; however venlafaxine decreased the IBA-1 only in the DRG. No changes in the GFAP level in both structures were observed after any of listed above antidepressants administration. Chronic minocycline treatment enhanced amitriptyline and milnacipran, but did not fluoxetine analgesia under neuropathic pain in rats. Our results suggest that nerve injury-induced pain is related with the activation of microglia, which is diminished by fluoxetine treatment in the neuropathic pain model.

  19. Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder.

    PubMed

    Meltzer, H; Bastani, B; Jayathilake, K; Maes, M

    1997-07-01

    It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

  20. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  1. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429

  2. Stenting in the Treatment of Acute Ischemic Stroke: Literature Review

    PubMed Central

    Samaniego, Edgar A.; Dabus, Guilherme; Linfante, Italo

    2011-01-01

    Recanalization of acute large artery occlusions is a strong predictor of good outcome. The development of thrombectomy devices resulted in a significant improvement in recanalization rates compared to thrombolytics alone. However, clinical trials and registries with these thrombectomy devices in acute ischemic stroke (AIS) have shown recanalization rates in the range of 40–81%. The last decade has seen the development of nickel titanium self-expandable stents (SES). These stents, in contrast to balloon-mounted stents, allow better navigability and deployment in tortuous vessels and therefore are optimal for the cerebral circulation. SES were initially used for stent-assisted coil embolization of intracranial aneurysms and for treatment of intracranial stenosis. However, a few authors have recently reported feasibility of deployment of SES in AIS. The use of these devices yielded higher recanalization rates compared to traditional thrombectomy devices. Encouraged by these results, retrievable SES systems have been recently used in AIS. These devices offer the advantage of resheathing and retrieving of the stent even after full deployment. Some of these stents can also be detached in case permanent stent placement is needed. Retrievable SES are being used in Europe and currently tested in clinical trials in the United States. We review the recent literature in the use of stents for the treatment of AIS secondary to large vessel occlusion. PMID:22163225

  3. Endovascular treatment of acute type B dissection complicating aortic coarctation.

    PubMed

    Kassaian, Seyed Ebrahim; Abbasi, Kyomars; Mousavi, Mehdi; Sahebjam, Mohammad

    2013-01-01

    Surgical treatment poses a high risk to patients with concomitant aortic coarctation and dissection, and an interventional approach could be an alternative. We describe the case of a 52-year-old man with a long history of untreated hypertension and aortic coarctation who emergently presented at our institution with an acute Stanford type B dissection. The patient's elevated serum creatinine level, perfusion deficit in the right lower limb, and hypertension did not respond to medical therapy, and he did not consent to surgery. By endovascular means, we used a self-expandable stent-graft to cover the entry point of the dissection; then, we deployed a balloon-expandable bare-metal stent to correct residual stenosis. To our knowledge, this is the first report of the endovascular treatment of aortic coarctation complicated by type B dissection.

  4. [Evidence for treatment of acute syndesmosis injuries in sports].

    PubMed

    Best, R; Mauch, F; Bauer, G

    2013-06-01

    Injuries of the distal syndesmosis often accompany acute ankle sprains especially in professional team sports. While small partial syndesmosis lesions can often be missed as a consequence of impressive symptoms due to ventrolateral capsuloligamentous injuries, higher grade injuries of the syndesmosis can mostly be diagnosed without any problem. Furthermore, there is a consensus concerning the necessity of operative treatment in significantly unstable situations as well concerning conservative treatment of incomplete partial lesions. Consequently, the greatest challenge regarding diagnostic tools, quantification and optimal therapy arises in the most common form of sport-associated, complete or partial lesions of the distal syndesmosis. This review article summarizes sports-associated injuries of the distal tibiofibular syndesmosis considering the current literature and placing the emphasis on the anatomy, pathobiomechanics, diagnostics and therapy of syndesmosis lesions from an evidence-based viewpoint.

  5. Hippocampal HDAC4 contributes to postnatal fluoxetine-evoked depression-like behavior.

    PubMed

    Sarkar, Ambalika; Chachra, Parul; Kennedy, Pamela; Pena, Catherine J; Desouza, Lynette A; Nestler, Eric J; Vaidya, Vidita A

    2014-08-01

    Fluoxetine treatment in adulthood evokes antidepressant and anxiolytic responses. Paradoxically, postnatal fluoxetine (PNFlx) induces persistent depression- and anxiety-like behaviors. The mechanistic underpinnings of this paradox remain poorly understood. Here, we examined specific molecular changes in the rat hippocampus that accompany perturbed emotionality observed across life following PNFlx. PNFlx-induced hippocampal gene regulation observed in microarray and quantitative PCR studies indicate functional enrichment of genes involved in response to organic substances, protein kinase pathways, DNA binding, and transcriptional repression. We noted specific transcripts (Hdac4, mammalian target of rapamycin (mTOR), Gnai1, protein kinase C gamma (Prkcc), and hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1)) that were consistently dysregulated across life, and selectively influenced by postnatal, but not adult, fluoxetine. Increased histone deacetylase-4 (HDAC4) recruitment, accompanied by decreased activating histone acetylation marks at the mTOR and Gnai1 promoters, indicate a role for HDAC4 in PNFlx-mediated gene dysregulation. Strikingly, coadministration of the HDAC inhibitor sodium butyrate with PNFlx prevented the dysregulation of Hdac4 and mTOR, and the emergence of depression- and anxiety-like behavior. Importantly, we also find that retreatment of PNFlx animals with fluoxetine in adulthood reversed the increased Hdac4 expression, prevented HDAC4 recruitment to the mTOR and Gnai1 promoters, and attenuated the decline in mTOR and Gnai1 expression, coincident with normalization of PNFlx-evoked depression- and anxiety-like behavior. Further, we show that viral-mediated hippocampal overexpression of Hdac4 was sufficient to induce depression-, but not anxiety-, like behavior in adulthood. Our results highlight the unique nature of molecular signatures evoked by PNFlx, and implicate HDAC4 in the dysregulated gene expression and emergence of

  6. [Consensus conference on acute bronchiolitis (IV): Treatment of acute bronchiolitis. Review of scientific evidence].

    PubMed

    González de Dios, J; Ochoa Sangrador, C

    2010-04-01

    A review of the evidence on treatment of acute bronchiolitis is presented. There is sufficient evidence on the lack of effectiveness of most interventions tested in bronchiolitis. Apart from oxygen therapy, fluid therapy, aspiration of secretions and ventilation support, few treatment options will be beneficial. There are doubts about the efficacy of inhaled bronchodilators (salbutamol or adrenaline), with or without hypertonic saline solution, suggesting that these options should be selectively used as therapeutic trials in moderate-severe bronchiolitis. Heliox and non-invasive ventilation techniques, methylxanthine could be used in cases with respiratory failure, in patients with apnea, and surfactant and inhaled ribavirin in intubated critically ill patients. The available evidence does not recommend the use of oral salbutamol, subcutaneous adrenaline, anticholinergic drugs, inhaled or systemic corticosteroids, antibiotics, aerosolized o intravenous immunoglobulin, respiratory physiotherapy and others (nitric oxide, recombinant human deoxyribonuclease, recombinant interferon, nebulised furosemide and so on).

  7. Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines

    PubMed Central

    Mundalil Vasu, Mahesh; Anitha, Ayyappan; Takahashi, Taro; Thanseem, Ismail; Iwata, Keiko; Asakawa, Tetsuya; Suzuki, Katsuaki

    2016-01-01

    Evidence suggests neuroprotective effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on the developed neurons in the adult brain. In contrast, the drug may be deleterious to immature or undifferentiated neural cells, although the mechanism is unclear. Recent investigations have suggested that microRNAs (miRNA) may be critical for effectiveness of psychotropic drugs including SSRI. We investigated whether fluoxetine could modulate expressions of neurologically relevant miRNAs in two neuroblastoma SK-N-SH and SH-SY5Y cell lines. Initial screening results revealed that three (miR-489, miR-572 and miR-663a) and four (miR-320a, miR-489, miR-572 and miR-663a) miRNAs were up-regulated in SK-N-SH cells and SH-SY5Y cells, respectively, after 24 hours treatment of fluoxetine (1–25 μM). Cell viability was reduced according to the dose of fluoxetine. The upregulation of miR-572 and miR-663a was consistent in both the SH-SY5Y and SK-N-SH cells, confirmed by a larger scale culture condition. Our data is the first in vitro evidence that fluoxetine could increase the expression of miRNAs in undifferentiated neural cells, and that putative target genes of those miRNAs have been shown to be involved in fundamental neurodevelopmental processes. PMID:27716787

  8. Emerging New Approaches for the Treatment of Acute Promyelocytic Leukemia

    PubMed Central

    Park, Jae; Jurcic, Joseph G.; Rosenblat, Todd; Tallman, Martin S.

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emhasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed. PMID:23556100

  9. Recent advances and novel treatment paradigms in acute lymphocytic leukemia

    PubMed Central

    Papadantonakis, Nikolaos; Advani, Anjali S.

    2016-01-01

    This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment. PMID:27695616

  10. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children.

    PubMed

    Hoberman, Alejandro; Paradise, Jack L; Rockette, Howard E; Kearney, Diana H; Bhatnagar, Sonika; Shope, Timothy R; Martin, Judith M; Kurs-Lasky, Marcia; Copelli, Susan J; Colborn, D Kathleen; Block, Stan L; Labella, John J; Lynch, Thomas G; Cohen, Norman L; Haralam, MaryAnn; Pope, Marcia A; Nagg, Jennifer P; Green, Michael D; Shaikh, Nader

    2016-12-22

    Background Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media. Methods We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms. Results Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001). Conclusions Among children 6 to 23 months of age with acute

  11. Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

    ERIC Educational Resources Information Center

    Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

    2004-01-01

    Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

  12. 77 FR 60126 - Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ...; Formerly 2008N-0004] Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment... Media: Developing Drugs for Treatment.'' This guidance addresses FDA's current thinking regarding the... treatment of acute bacterial otitis media (ABOM). This guidance finalizes the revised draft guidance of...

  13. The effect of combined administration of ethanol and sertraline, fluoxetine and citalopram on rabbit EEG.

    PubMed

    Pietrzak, Bogusława; Czarnecka, Elzbieta

    2003-06-01

    In this study we have decided to examine acute interaction of ethanol with some drugs that belong to selective serotonin inhibitor (SSRI) group. Therefore, the influence of sertraline, fluoxetine and citalopram on the effect of ethanol on EEG of rabbits (frontal cortex, hippocampus, MRF) was tested. Sertraline (10mg/kg i.p.), fluoxetine (10mg/kg i.p.) and citalopram (5mg/kg i.p.) were given 30min before ethanol injection in a dose 0.8g/kg i.v. Ethanol caused the increase of the slow frequencies (0.5-4cps) in the recording, as well as a marked decrease of the fastest frequencies (13-30 and 30-45cps). Sertraline, fluoxetine and citalopram (given before ethanol) prevented the increase in the slow frequencies (0.5-4cps) in the recordings from the frontal cortex and hippocampus, which indicates on antagonism inhibitory action of ethanol. These drugs administered together with ethanol may increase its influence on fast frequencies. This effect depends on brain structure and drug.

  14. Psychogenic excoriation responding to fluoxetine: a case report.

    PubMed

    Sharma, Himanshu

    2008-04-01

    Compulsive skin picking, 'acne excoriee', neurotic (psychogenic) excoriation, dermatotillomania, occurring in 2% dermatology patients mostly in women, is a result of excessive scratching, picking, gouging or squeezing of the skin using teeth, tweezers, nail files, pins and knives, etc. The lesions are usually found on face and also on upper limbs and upper back, areas patients can easily reach. They may occur in absence or in response to skin pathology or sensation of itching. A young female patient attended OPD with the complaints of multiple excoriated lesions over the face, arms and forearms. The diagnosis was psychogenic excoriation which is an uncommon psychodermatological condition. She was treated with fluoxetine and behaviour therapy. The patient recovered fully with above treatment at the end of 3 months. Psychogenic excoriation is an uncommon psychodermatological condition which responds well to selective serotonin reuptake inhibitors and behaviour therapy (habit reversal training).

  15. Application of simplified bioclean apparatuses for treatment of acute leukemia.

    PubMed

    Hasegawa, H; Horiuchi, A

    1983-01-01

    We used a portable horizontal laminar-air-flow clean bed and an open horizontal laminar-air-flow fan (clean wall unit) for treating patients with acute leukemia. The level of cleanliness as shown in the nonviable and viable particle counts was class 100 and class 1,000 at the head and foot, respectively, of the bed in the clean-bed rooms, while it was class 100 and class 10,000 respectively, in the clean-wall-unit rooms. The level of cleanliness in the open wards, on the other hand, was class 1,000,000. The incidence of infectious complications in the clean-bed rooms was 3.1/100 days when the granulocyte count was 1,000/mm3 or less, 3.9/100 days when the count was 500/mm3 or less and 6.1/100 days when it was 100/mm3 or less. In the clean-wall-unit rooms, these values were 3.1, 3.7 and 7.1, respectively, while in the open wards they were 4.6, 6.1 and 15.0. Thus, it was ascertained that, as the granulocyte count decreased, the incidence of infectious complications became significantly higher in the open wards than in the clean-bed rooms or the clean-wall-unit rooms. No complication of pneumonia was found in 37 patients with acute leukemia in the clean-bed rooms or in 40 in the clean-wall-unit rooms. Among 36 patients treated in the open wards, on the other hand, the complication of pneumonia was found in four. From the above results, it is believed that the use of clean-bed rooms or clean-wall-unit rooms is an extremely effective supplementary treatment method for preventing respiratory tract infection complications in patients with acute leukemia.

  16. [CHANGES OF A TREATMENT PROGRAM FOR AN ACUTE PANCREATITIS].

    PubMed

    Kostyrnoy, O V; Kosenko, A V; Bayomi, Imad Mokhamed Abdel S K

    2015-11-01

    Pathogenetically substantiated program of complex diagnosis, prophylaxis and treatment of purulent-necrotic complications (PNC) was elaborated for improvement of results of the necrotic pancreatitis treatment. With the objective to study the PNC pathogenesis and a probation of new preparations for local treatment the experimantal simulation of the disease was accomplished. There was proved, that during the disease course the integrity of pancreatic ductal system is disordered . A 42-year experience of treatment of an acute pancreatitis was analyzed. In I period (1970 - 1980) the operative interventions were conducted; in 11 period (1981 - 1991)--a scientifically substantiated conservative therapy; in III period (1992 - 2000)--the diagnostic procedures possibilities were extended, and operative intervention were performed in accordance to severe indications. There was established, that the main cause of PNC is a secondary microbal contamination occurrence on the third-fifth postoperative days, the immediate manipulations on pancreatic gland are forbidden; a one-time surgical processing of the necrosis foci is insufficient; the staged necrsequestrectomy constitutes the optimal operation.

  17. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.

    PubMed Central

    Levitan, R D; Shen, J H; Jindal, R; Driver, H S; Kennedy, S H; Shapiro, C M

    2000-01-01

    OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. PMID:11022398

  18. 5-HT2A receptors are involved in cognitive but not antidepressant effects of fluoxetine.

    PubMed

    Castañé, Anna; Kargieman, Lucila; Celada, Pau; Bortolozzi, Analía; Artigas, Francesc

    2015-08-01

    The prefrontal cortex (PFC) plays a crucial role in cognitive and affective functions. It contains a rich serotonergic (serotonin, 5-HT) innervation and a high density of 5-HT receptors. Endogenous 5-HT exerts robust actions on the activity of pyramidal neurons in medial PFC (mPFC) via excitatory 5-HT2A and inhibitory 5-HT1A receptors, suggesting the involvement of 5-HT neurotransmission in cortical functions. However, the underlying mechanisms must be elucidated. Here we examine the role of 5-HT2A receptors in the processing of emotional and cognitive signals evoked by increasing the 5-HT tone after acute blockade of the 5-HT transporter. Fluoxetine (5-20mg/kg i.p.) dose-dependently reduced the immobility time in the tail-suspension test in wild-type (WT) and 5-HT2Aknockout (KO2A) mice, with non-significant differences between genotypes. Fluoxetine (10mg/kg i.p.) significantly impaired mice performance in the novel object recognition test 24h post-administration in WT, but not in KO2A mice. The comparable effect of fluoxetine on extracellular 5-HT in the mPFC of both genotypes suggests that presynaptic differences are not accountable. In contrast, single unit recordings of mPFC putative pyramidal neurons showed that fluoxetine (1.8-7.2mg/kg i.v.) significantly increased neuronal discharge in KO2A but not in WT mice. This effect is possibly mediated by an altered excitatory/inhibitory balance in the PFC in KO2A mice. Overall, the present results suggest that 5-HT2A receptors play a detrimental role in long-term memory deficits mediated by an excess 5-HT in PFC.

  19. The psychoactive pollutant fluoxetine compromises antipredator behaviour in fish.

    PubMed

    Martin, Jake M; Saaristo, Minna; Bertram, Michael G; Lewis, Phoebe J; Coggan, Timothy L; Clarke, Bradley O; Wong, Bob B M

    2017-03-01

    Pharmaceuticals are increasingly being detected in aquatic ecosystems worldwide. Particularly concerning are pharmaceutical pollutants that can adversely impact exposed wildlife, even at extremely low concentrations. One such contaminant is the widely prescribed antidepressant fluoxetine, which can disrupt neurotransmission and behavioural pathways in wildlife. Despite this, relatively limited research has addressed the behavioural impacts of fluoxetine at ecologically realistic exposure concentrations. Here, we show that 28-day fluoxetine exposure at two ecologically relevant dosages-one representing low surface water concentrations and another representing high effluent flow concentrations-alters antipredator behaviour in Eastern mosquitofish (Gambusia holbrooki). We found that fluoxetine exposure at the lower dosage resulted in increased activity levels irrespective of the presence or absence of a predatory dragonfly nymph (Hemianax papuensis). Additionally, irrespective of exposure concentration, fluoxetine-exposed fish entered the predator 'strike zone' more rapidly. In a separate experiment, fluoxetine exposure reduced mosquitofish freezing behaviour-a common antipredator strategy-following a simulated predator strike, although, in females, this reduction in behaviour was seen only at the lower dosage. Together, our findings suggest that fluoxetine can cause both non-monotonic and sex-dependent shifts in behaviour. Further, they demonstrate that exposure to fluoxetine at environmentally realistic concentrations can alter antipredator behaviour, with important repercussions for organismal fitness.

  20. Acute urticaria and angioedema: diagnostic and treatment considerations.

    PubMed

    Frigas, Evangelo; Park, Miguel A

    2009-01-01

    Urticaria is defined as wheals consisting of three features: (i) central swelling of various sizes, with or without surrounding erythema; (ii) pruritus or occasional burning sensations; and (iii) the skin returning to normal appearance, usually within 1-24 hours. Angioedema is defined as: (i) abrupt swelling of the lower dermis and subcutis; (ii) occasional pain instead of pruritus; (iii) commonly involving the mucous membranes; and (iv) skin returning to normal appearance, usually within 72 hours. Acute urticaria and angioedema is defined by its duration (<6 weeks) compared with chronic urticaria and angioedema. The most common causes are infections, medications, and foods. The best tools in the evaluation of these patients are a comprehensive history and physical examination. There are a variety of skin conditions that may mimic acute urticaria and angioedema and the various reaction patterns associated with different drugs. Oral antihistamines are first-line treatment. In the event of a life-threatening reaction involving urticaria with angioedema, epinephrine may be needed to stabilize the patient. This review focuses on the value of a comprehensive clinical evaluation at the onset of symptoms. It underscores the importance of coordination of care among physicians, and the development of an action plan for evidence-based investigations, diagnosis, and therapy.

  1. Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment.

    PubMed

    Borron, S W; Baud, F J

    1996-09-01

    Cyanide poisoning presents in many forms. Industrial intoxications occur due to extensive use of cyanide compounds as reaction products. Smoke inhalation, a polyintoxication, is most often responsible for domestic cyanide poisonings. Suicidal poisonings are rare. Cyanogenic compounds may produce acute or subacute toxicity. Signs of cyanide poisoning include headache, vertigo, agitation, confusion, coma, convulsions and death. Definitive laboratory confirmation is generally delayed. Elevated plasma lactate, associated with cardiovascular collapse, should suggest cyanide intoxication. Immediate treatment includes 100% oxygen, assisted ventilation, decontamination, correction of acidosis and blood pressure support. Antidotes include oxygen, hydroxocobalamin, di-cobalt EDTA and methaemoglobin-inducers. Hydroxocobalamin is an attractive antidote due to its rapid cyanide binding and its lack of serious side-effects, even in the absence of cyanide intoxication. Sodium thiosulphate acts more slowly than other antidotes and is indicated in subacute cyanogen poisoning and as an adjunct to acute cyanide poisoning. Initial evaluation of antidotal efficacy is based on correction of hypotension and lactic acidosis; the final analysis rests on the degree of permanent central nervous system injury.

  2. [Surgical treatment of acute deep leg and pelvic vein trombosis].

    PubMed

    Gall, F; Husfeldt, K J

    1977-08-25

    In the last 3 years 93 cases of iliofermoral trombosis were treated by surgery. We prefer the method used by Brunner, but under general anaesthesia and using a Bentley-Autotransfusion-System (ATS). The average age of our patients was 55 years (age ranged between 17 and 87 years). No lethal pulmonary embolism was observed. 2, 1 percent of the patients died following apoplex or acute heart failure. Of 67 patients who were operated on 6 months ago or more 70 percent have no further complaints, 28 percent still have some residual edema and only 2 patients have a severe postthrombotic syndrome. 50 percent of 40 control-phlebograms demonstrated patency of all veins. 20 percent had short segmentary occlusions with definite signs of recanalisation, while in 27 percent of the cases occlusions of the lower leg and thigh were found, the iliac veins being free. Only 2 postoperative phlebograms showed a complete iliofemoral venous occlusion. Our results prove, that the operative thrombectomy is a successful method, with which the main complications of the iliofemoral thrombosis-pulmonary embolisation and postthrombotic syndrome-can difinitely be reduced. Also because of better long term results, the operative therapy of acute ilofemoral thrombosis should be generally prefered instead of conservative treatment.

  3. Acute renal and hepatic failure associated with allopurinol treatment.

    PubMed

    Fagugli, R M; Gentile, G; Ferrara, G; Brugnano, R

    2008-12-01

    Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.

  4. Sapacitabine in the treatment of acute myeloid leukemia.

    PubMed

    Norkin, Maxim; Richards, Ashley I

    2015-01-01

    Prognosis of elderly patients with acute myeloid leukemia (AML) remains poor and new treatment approaches are urgently needed. A novel nucleoside analog sapacitabine has recently emerged as a feasible agent because of its oral administration and acceptable toxicity profile. Clinical efficacy of sapacitabine, both as a single agent and in combination, has been evaluated in elderly AML patients or AML patients unfit for standard intensive chemotherapy. Response rates varied from 15 to 45% in phase II studies. Sapacitabine was overall well-tolerated with gastrointestinal and myelosuppression-related complications were the most common side effects. Unfortunately, in a phase III study sapacitabine showed no clinical superiority as compared to low-dose cytarabine (LDAC) in patients with AML. Another large phase III study comparing the combination of sapacitabine with decitabine to decitabine alone is currently ongoing and is expected to be completed by the end of 2015 or by the first half of 2016.

  5. Pharmacogenomics and the treatment of acute myeloid leukemia.

    PubMed

    Megías-Vericat, Juan Eduardo; Montesinos, Pau; Herrero, María José; Bosó, Virginia; Martínez-Cuadrón, David; Poveda, José Luis; Sanz, Miguel Ángel; Aliño, Salvador F

    2016-07-01

    Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous malignancy that is primarily treated with combinations of cytarabine and anthracyclines. Although this scheme remains effective in most of the patients, variability of outcomes in patients has been partly related with their genetic variability. Several pharmacogenetic studies have analyzed the impact of polymorphisms in genes encoding transporters, metabolizers or molecular targets of chemotherapy agents. A systematic review on all eligible studies was carried out in order to estimate the effect of polymorphisms of anthracyclines and cytarabine pathways on efficacy and toxicity of AML treatment. Other emerging genes recently studied in AML, such as DNA repair genes, genes potentially related to chemotherapy response or AML prognosis, have also been included.

  6. The potential contributing effect of ketorolac and fluoxetine to a spinal epidural hematoma following a cervical interlaminar epidural steroid injection: a case report and narrative review.

    PubMed

    Chien, George C Chang; McCormick, Zack; Araujo, Marco; Candido, Kenneth D

    2014-01-01

    Cervical interlaminar epidural steroid injections (ESIs) are commonly performed as one part of a multi-modal analgesic regimen in the management of upper extremity radicular pain. Spinal epidural hematoma (SEH) is a rare complication with a reported incidence ranging from 1.38 in 10,000 to 1 in 190,000 epidurals. Current American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians (ASIPP), and the International Spine Intervention Society (ISIS) recommendations are that non-steroidal anti-inflammatory drugs (NSAIDs) do not need to be withheld prior to epidural anesthesia. We report a case wherein intramuscular ketorolac and oral fluoxetine contributed to a SEH and tetraplegia following a cervical interlaminar (ESI). A 66 year-old woman with chronic renal insufficiency and neck pain radiating into her right upper extremity presented for evaluation and was deemed an appropriate CESI candidate. Cervical magnetic resonance imaging (MRI) revealed multi-level neuroforaminal stenosis and degenerative intervertebral discs. Utilizing a loss of resistance to saline technique, an 18-gauge Tuohy-type needle entered the epidural space at C6-7. After negative aspiration, 4 mL of saline with 80 mg of methyl-prednisolone was injected. Immediately thereafter, the patient reported significant spasmodic-type localized neck pain with no neurologic status changes. A decision was made to administer 30 mg intramuscular ketorolac as treatment for the spasmodic-type pain. En route home, she developed a sudden onset of acute tetraplegia. She was brought to the emergency department for evaluation including platelet and coagulation studies which were normal. MRI demonstrated an epidural hematoma extending from C5 to T7. She underwent a bilateral C5-T6 laminectomy with epidural hematoma evacuation and was discharged to an acute inpatient rehabilitation hospital. Chronic renal insufficiency, spinal stenosis, female gender, and increasing age have been

  7. Enhanced reactivity of 5-HT1A receptors in the rat dorsal periaqueductal gray matter after chronic treatment with fluoxetine and sertraline: evidence from the elevated T-maze.

    PubMed

    Zanoveli, Janaina Menezes; Nogueira, Regina Lúcia; Zangrossi, Hélio

    2007-03-01

    Behavioral evidence indicates that sensitization of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal gray (DPAG) may underlie the therapeutic effect of serotonin reuptake inhibitors (SRIs) in panic disorder. These results were obtained from studies using animal models that associate escape behavior with panic attacks, such as the elevated T-maze. In this test, chronic administration of the non-selective SRI imipramine enhances the inhibitory effect on escape caused by the intra-DPAG injection of the 5-HT1A receptor agonist 8-OH-DPAT. We here evaluated the generality of this finding by investigating the effect of chronic administration of two selective SRIs (SSRIs), fluoxetine and sertraline, on the reactivity of the rat DPAG 5-HT1A receptors. The results showed that both SSRIs inhibited escape behavior in the elevated T-maze, suggestive of a panicolytic-like effect. Whereas intra-DPAG injection of a low dose of 8-OH-DPAT (0.4nmol) had no effect on escape in control animals, it significantly enhanced the inhibitory effect caused by the SSRIs on this response. Microinjection of 8-OH-DPAT in SSRI-treated rats also inhibited the acquisition of inhibitory avoidance, another defensive response measured by the elevated T-maze. The results indicate that chronic administration of fluoxetine and sertraline sensitizes 5-HT1A receptors in the DPAG. Overall, they support the view that facilitation of 5-HT1A receptor-mediated neurotransmission in the DPAG is implicated in the therapeutic effect of SRIs on panic disorder.

  8. [Intracranial pressure targeted treatment in acute bacterial meningitis increased survival].

    PubMed

    Glimåker, Martin; Johansson, Bibi; Halldorsdottir, Halla; Wanecek, Michael; Elmi-Terander, Adrian; Bellander, Bo-Michael

    2014-12-16

    To evaluate the efficacy of intracranial pressure (ICP)-targeted treatment, compared to standard intensive care, in adults with community acquired acute bacterial meningitis (ABM) and severely impaired consciousness, a prospectively designed intervention-control comparison study was performed. Included were patients with confirmed ABM and severely impaired mental status on admission. Fifty-two patients, given ICP-targeted treatment at a neuro-intensive care unit, and 53 control cases, treated with conventional intensive care, were included. All patients received intensive care with me-chanical ventilation, sedation, antibiotics and corticosteroids according to current guidelines. ICP-targeted treatment was performed in the intervention group, aiming at ICP 50 mmHg. The mortality was significantly lower in the intervention group compared to controls, 5/52 (10%) versus 16/53 (30%). Furthermore, only 17 patients (32%) in the control group fully recovered, compared to 28 (54%) in the intervention group. Early neuro-intensive care using ICP-targeted therapy reduces mortality and improves the overall outcome in adult patients with ABM and severely impaired mental status on admission.

  9. New agents approved for treatment of acute staphylococcal skin infections

    PubMed Central

    Tatarkiewicz, Jan; Staniszewska, Anna

    2016-01-01

    Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics. PMID:27904526

  10. Treatment of simultaneous acute antibody-mediated rejection and acute cellular rejection with alemtuzumab in kidney transplantation: a case report.

    PubMed

    Jirasiritham, S; Khunprakant, R; Techawathanawanna, N; Jirasiritham, Si; Mavichak, V

    2010-04-01

    This is a case report of a living related donor kidney transplantation using basiliximab induction and maintenance immunosuppression with cyclosporine, mycophenolate sodium, and steroid. On the second posttransplant day, the patient developed acute antibody-mediated rejection, which was treated with plasmapheresis and intravenous immunoglobulin (IVIG). Five days later, the graft had still not responded to the treatment. Another biopsy revealed additional acute cellular rejection (Banff IIA). As alemtuzumab can rapidly deplete T and B lymphocytes, monocytes, and natural killer cells, the patient was treated with alemtuzumab (30 mg subcutaneously) together with methylprednisolone (500 mg) and two more plasmaphereses. The kidney graft responded within 48 hours, producing more than 4 L of urine per day. The total lymphocyte decreased from 530/microL to 50/microL remaining in the 50 to 220/microL range. The patient received valgancyclovir and cotrimoxazole as infection prophylaxis. The kidney graft responded well to the rescue treatment and the patient was discharged with a serum creatinine of 1.1 mg/mL and has been uneventfully followed in the outpatient clinic for 8 months. Today, with the potent, effective, and selective immunosuppressive regimens, the rate and severity of acute cellular rejection in kidney transplantation has decreased in most centers. However, the rate of acute antibody-mediated rejection has increased to levels greater than those of acute cellular rejection in many centers. Acute antibody-mediated rejection is more difficult and expensive to treat successfully. The treatment of acute antibody-mediated rejection included plasmapheresis and IVIG. Herein we have reported a case of kidney transplantation simultaneously developing acute antibody-mediated and acute cellular rejection; the patient was successfully treated with alemtuzumab.

  11. Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus.

    PubMed

    Kobayashi, Katsunori; Ikeda, Yumiko; Asada, Minoru; Inagaki, Hirofumi; Kawada, Tomoyuki; Suzuki, Hidenori

    2013-01-01

    The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This "dematuration" is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions.

  12. Fluoxetine Monotherapy in Attention-Deficit/Hyperactivity Disorder and Comorbid Non-Bipolar Mood Disorders in Children and Adolescents

    ERIC Educational Resources Information Center

    Quintana, Humberto; Butterbaugh, Grant J.; Purnell, William; Layman, Ann K.

    2007-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for…

  13. Cortisol level in men with major depressive disorder treated with fluoxetine or imipramine.

    PubMed

    Piwowarska, Jadwiga; Dryll, Karolina; Szelenberger, Waldemar; Pachecka, Jan

    2008-01-01

    The aim of this research was to find out whether increased plasma cortisol levels appear in unipolar or bipolar patients with major depressive disorder (MDD) and whether the effective antidepressant treatment by imipramine and fluoxetine leads to regulation of the cortisol level. Cortisol levels were studied in two groups of patients with major depressive disorder: unipolar and bipolar patients treated with fluoxetine (doses: 20-60 mg/day). This group included 5 patients (age 29-46 yr); unipolar and bipolar subjects treated with imipramine (50-150 mg/day), this group included 5 patients (aged 24-70 yr). Cortisol and fluoxetine or imipramine plasma levels were assessed using HPLC methods: before treatment, after 3, 6 and 24 h of drug administration as well as in the 2nd, 4th, 6th, and 8th week of antidepressant treatment. HPLC methods were previously validated. The research conducted and the clinical data may be useful for proving the essential role of enhanced HPA axis activity for the pathogenesis and depressive disorder proceedings.

  14. CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: intraindividual variability and plasma concentration correlations.

    PubMed

    Alfaro, C L; Lam, Y W; Simpson, J; Ereshefsky, L

    2000-01-01

    The authors report the CYP2D6 inhibitory effects of fluoxetine, paroxetine, sertraline, and venlafaxine in an open-label, multiple-dose, crossover design. Twelve CYP2D6 extensive metabolizers were phenotyped, using the dextromethorphan/dextrorphan (DM/DX) urinary ratio, before and after administration of fluoxetine 60 mg (loading dose strategy), paroxetine 20 mg, sertraline 100 mg, and venlafaxine 150 mg. Paroxetine, sertraline, and venlafaxine sequences were randomized with 2-week washouts between treatments; fluoxetine was the last antidepressant (AD) administered. Comparing within groups, baseline DM/DX ratios (0.017) were significantly lower than DM/DX ratios after treatment (DM/DXAD) with fluoxetine (0.313, p < 0.0001) and paroxetine (0.601, p < 0.0001) but not for sertraline (0.026, p = 0.066) or venlafaxine (0.023, p = 0.485). Between groups, DM/DXAD ratios were significantly higher for fluoxetine and paroxetine compared to sertraline and venlafaxine. No differences between DM/DXAD ratios were found for fluoxetine and paroxetine although more subjects phenocopied to PM status after receiving the latter (42% vs. 83%; chi 2 = 4.44, p = 0.049, df = 1). Similarly, no differences between DM/DXAD ratios were found for sertraline and venlafaxine. Of note, the DM/DXAD for 1 subject was much lower after treatment with paroxetine (0.058) compared to fluoxetine (0.490), while another subject exhibited a much lower ratio after treatment with fluoxetine (0.095) compared to paroxetine (0.397). Significant correlations between AD plasma concentration and DM/DXAD were found for paroxetine (r2 = 0.404, p = 0.026) and sertraline (r2 = 0.64, p = 0.002) but not fluoxetine or venlafaxine. In addition, DM/DXAD correlated with baseline isoenzyme activity for paroxetine, sertraline, and venlafaxine groups. These results demonstrate the potent, but variable, CYP2D6 inhibition of fluoxetine and paroxetine compared to sertraline and venlafaxine. CYP2D6 inhibition may be related, in

  15. Effects of fluoxetine and melatonin on mood, sleep quality and body mass index in postmenopausal women.

    PubMed

    Chojnacki, C; Walecka-Kapica, E; Klupinska, G; Pawlowicz, M; Blonska, A; Chojnacki, J

    2015-10-01

    Frequent mood and sleep disorders and increased appetite leading to obesity are observed in postmenopausal women. Due to the limitations of hormone replacement therapy the researchers look for other treatment regimes. The aim of the study was to evaluate the efficacy of fluoxetine and melatonin in the treatment of these disorders. The study included 64 overweight postmenopausal women, aged 54 - 65 years, with increased appetite. They were randomly assigned in 2 groups. In group I (n = 30) fluoxetine (20 mg in the morning) and placebo (in the evening) were administered for 24 weeks. Group II (n = 34) received fluoxetine (20 mg in the morning) and melatonin (5 mg in the evening) in the same period of time. Hamilton anxiety rating scale (HARS), Beck depression scale (BDI), the insomnia severity index (ISI) and body mass index (BMI) were used to assess the health status and the treatment efficacy. After 24 weeks, comparable and statistically significant reduction in the level of anxiety and depression was obtained in both groups. In group I, the ISI decreased from 14.9 ± 2.5 points to 10.9 ± 1.9 points (P < 0.05) and in group II from 15.8 ± 2.4 points to 7.7 ± 1.5 points (P < 0.001). In group I no reduction in BMI was achieved whereas in group II this index decreased from 30.9 ± 3.1 to 26.3 ± 3.2 (P < 0.05). We conclude that combined administration of fluoxetine and melatonin was useful option to treat mood, sleep and appetite disorders in postmenopausal women.

  16. Differential effects of fluoxetine and venlafaxine on memory recognition: possible mechanisms of action.

    PubMed

    Carlini, Valeria Paola; Poretti, María Belén; Rask-Andersen, Mathias; Chavan, Rohit A; Ponzio, Marina F; Sawant, Rahul S; de Barioglio, Susana Rubiales; Schiöth, Helgi B; de Cuneo, Marta Fiol

    2012-08-07

    Serotonin-specific reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are antidepressant drugs commonly used to treat a wide spectrum of mood disorders (Wong and Licinio, 2001). Although they have been clinically used for more than 50 years, the molecular and cellular basis for the action of SSRIs and SNRIs is not clear. Considering that the changes in gene expression involved in the action of antidepressant drugs on memory have not been identified, in this study we investigated the impact of chronic treatment with a SSRI (fluoxetine) and a SNRI (venlafaxine) on the mRNA expression of genes related to memory cascade in the mouse hippocampus, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), nitric oxide synthase 1 (NOS1), neurotrophic tyrosine kinase receptor type 2 (TrKB), mitogen-activated protein kinases (MAPK/ERK) and serotonin transporter (SERT). Animals treated with fluoxetine 10 mg/Kg/day for 28 days showed a significant decrease in the percentage of time spent in the novel object recognition test (p≤0.005) and induced MAPK1/ERK2 down-regulation (p=0.005). Our results suggest that the effect on cognition could probably be explained by fluoxetine interference in the MAPK/ERK memory pathway. In contrast, chronic treatment with venlafaxine did not reduce MAPK1/ERK2 expression, suggesting that MAPK1/ERK2 down-regulation is not a common effect of all antidepressant drugs. Further studies are needed to examine the effect of chronic fluoxetine treatment on the ERK-CREB system, and to determine whether there is a causal relationship between the disruption of the ERK-CREB system and the effect of this antidepressant on memory performance.

  17. The expression of HoxB5 and SPC in neonatal rat lung after exposure to fluoxetine

    PubMed Central

    Taghizadeh, Razieh; Taghipour, Zahra; Karimi, Akbar; Shamsizadeh, Ali; Taghavi, Mohammad Mohsen; Shariati, Mahdi; Shabanizadeh, Ahmad; Jafari Naveh, Hamid Reza; Bidaki, Reza; Aminzadeh, Fariba

    2016-01-01

    Objective Approximately 10% of pregnant women suffer from pregnancy-associated depression. Fluoxetine, as a selective serotonin reuptake inhibitor, is being employed as a therapy for depressive disorders. The present study aimed to determine the effects of fluoxetine on neonatal lung development. Methods Thirty pregnant Wistar rats (weighing 200–250 g) were treated daily with 7 mg/kg fluoxetine from gestation day 0 to gestation day 21, via gavage. The control group received a similar volume of distilled water only. Following delivery, the newborns and their lungs were immediately weighed in both of the groups. The right lung was fixed for histological assessments while the left lung was used for evaluation of the expression of SPC and HoxB5 by the real-time polymerase chain reaction method. Results Results have indicated that even though the body weight and the number of neonatal rats in both groups were the same, the lung weight of neonates exposed to fluoxetine was significantly different compared to the control group (P<0.05). Expression of both genes was increased, nonetheless, only elevation of HoxB5 was significant (P<0.05). Histological studies demonstrated that lung tissue in the fluoxetine treatment group morphologically appears to be similar to the pseudoglandular phase, whereas the control group lungs experienced more development. Conclusion According to the upregulated expression of HoxB5 concerning histological findings, results of the present study showed that fluoxetine can influence lung growth and may in turn lead to delay in lung development. So establishment of studies to identify the effects of antidepressant drugs during pregnancy is deserved. PMID:27843293

  18. Treatment of Experimental Acute Radiation Disease in Mice with Probiotics, Quinolones, and General Gnotobiological Isolation

    DTIC Science & Technology

    1998-09-01

    Armed Forces Ra ioloy Research Institute Treatment of Experimental Acute Radiation Disease in Mice with Probiotics , Quinolones, and General...Gnotobiological Isolation Russia State Medical University 19990119 114 Treatment of Experimental Acute Radiation Disease in Mice with Probiotics , Quinolones...effects of antibiotics and probiotics (Bifidobacterium and Lactobacillus) in mice irradiated with 7 Gy. The effects were studied in normal mice and mice

  19. Acute Myeloid Leukemia: Advancements in Diagnosis and Treatment

    PubMed Central

    Yu, Meng-Ge; Zheng, Hu-Yong

    2017-01-01

    Objective: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. Data Sources: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned. Study Selection: This article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML. Results: We described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. Conclusion: Gene sequencing techniques should set the basis for next-generation diagnostic

  20. New paradigms in the recognition and acute treatment of migraine.

    PubMed

    Sheftell, Fred D; Tepper, Stewart J

    2002-01-01

    It would be ideal if clinical decisions regarding acute migraine treatment could be made on the basis of three parameters: a critical appraisal of available scientific evidence, clinical experience (including knowledge of the individual patient and his/her attack characteristics), and, of course, patient preferences. Patients are likely to prefer agents that offer rapid relief, pain-free status within 2 hours, no recurrence or need for rescue medication, extended time to recurrence (if present), consistency of therapeutic effect over multiple attacks, oral administration. good tolerability, safety, and minimal drug interactions. Fortunately, a number of specific therapies now are available which place these objectives within the patient's reach. Ongoing barriers to optimal migraine care include underrecognition, underconsultation, undertreatment, restrictions imposed by insurance companies, and exaggerated concerns regarding the safety of the triptans. Overcoming these barriers is likely to prove a more important contribution to patient care than endeavoring to establish the relative merits of one triptan over another. We have described in detail a number of strategies for improving recognition and treatment of migraine. Many headache specialists now believe that recurrent episodes of disabling headache, with a stable pattern over years, should be viewed as migraine until proven otherwise. In the end, this may represent the most useful paradigm in the primary care setting, where time is of the essence. Studies to validate this approach are needed. Acute treatment intervention that is based on scientific evidence, clinical experience, and patients' needs and desires will provide better outcomes than those presently obtained. Preliminary evidence favors early intervention with oral triptans, and randomized, prospective, double-blind, placebo-controlled studies, ideally employing a crossover design, are required to confirm this. The US Consortium's evidence

  1. Evaluation and treatment of acute low back pain.

    PubMed

    Kinkade, Scott

    2007-04-15

    Acute low back pain with or without sciatica usually is self-limited and has no serious underlying pathology. For most patients, reassurance, pain medications, and advice to stay active are sufficient. A more thorough evaluation is required in selected patients with "red flag" findings associated with an increased risk of cauda equina syndrome, cancer, infection, or fracture. These patients also require closer follow-up and, in some cases, urgent referral to a surgeon. In patients with nonspecific mechanical low back pain, imaging can be delayed for at least four to six weeks, which usually allows the pain to improve. There is good evidence for the effectiveness of acetaminophen, nonsteroidal anti-inflammatory drugs, skeletal muscle relaxants, heat therapy, physical therapy, and advice to stay active. Spinal manipulative therapy may provide short-term benefits compared with sham therapy but not when compared with conventional treatments. Evidence for the benefit of acupuncture is conflicting, with higher-quality trials showing no benefit. Patient education should focus on the natural history of the back pain, its overall good prognosis, and recommendations for effective treatments.

  2. Beginning treatment for pediatric acute myeloid leukemia: the family connection.

    PubMed

    McGrath, Pam; Paton, Mary Anne; Huff, Nicole

    2005-01-01

    There is a loud silence on psycho-oncology research in relation to pediatric Acute Myeloid Leukemia (AML). This article is part of a series that begins to address the psycho-social hiatus. The present article documents the less obvious, often hidden, aspect of beginning treatment for pediatric AML--the "behind the scenes" experience of the home and family connection. The findings are from the first stage of a five year longitudinal study that examines through qualitative research the experience of childhood leukemia from the perspective of the child, siblings and parents. Open-ended interviews, audio-recorded and transcribed verbatim, were thematically analyzed with the assistance of the Non-numerical Unstructured Data by processes of Indexing Searching and Theory-building (NUD*IST) computer program. The findings emphasize the disruption to normalcy in relation to home life, school, and work, which is exacerbated for families who relocate for specialist treatment. The findings emphasise the need for support for families coping with childhood AML.

  3. Successful implementation of spacer treatment guideline for acute asthma

    PubMed Central

    Powell, C; Maskell, G; Marks, M; South, M; Robertson, C; LENNEY, W.

    2001-01-01

    AIMS—To develop and implement an evidence based guideline for the treatment of acute asthma using a metered dose inhaler and spacer combination.
METHODS—Defined strategies were used for the development and implementation of a guideline, assessed by a prospective, descriptive, study using notes review, and patient, nursing, and medical staff telephone contact. The setting was a tertiary referral hospital in Victoria, Australia with 25 000 yearly admissions, and asthma accounting for about 7% of total. The first 200 children and families to use the guideline after its introduction were evaluated.
RESULTS—A total of 191 (95.5%) children were treated according to the guideline. Six (3.0%) children were given nebulisers appropriately based on severity; five (2.5%) were given nebulisers at parental or child choice; and four (2.0 %) who did not have severe asthma, received nebulised treatment inappropriately.
CONCLUSIONS—Successful implementation of a new evidence based guideline can be achieved using specific strategies for promoting the application of research findings in the clinical arena.

 PMID:11159290

  4. Treatment of Adolescent and Young Adults with Acute Lymphoblastic Leukemia

    PubMed Central

    Ribera, Josep-Maria; Ribera, Jordi; Genescà, Eulàlia

    2014-01-01

    The primary objective of this review was to update and discuss the current concepts and the results of the treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALL in the AYA population, the main retrospective comparative studies stating the superiority of pediatric over adult-based protocols were reviewed. The most important prospective studies in young adults using pediatric inspired or pediatric unmodified protocols were also reviewed emphasizing their feasibility at least up to the age of 40 yr and their promising results, with event-free survival rates of 60–65% or greater. Results of trials from pediatric groups have shown that the unfavourable prognosis of adolescents is no more adequate. The majority of the older adolescents with ALL can be cured with risk-adjusted and minimal residual disease-guided intensive chemotherapy, without stem cell transplantation. However, some specific subgroups, which are more frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like), deserve particular attention. In summary, the advances in treatment of ALL in adolescents have been translated to young adults, and that explains the significant improvement in survival of these patients in recent years. PMID:25045460

  5. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    PubMed Central

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  6. Low molecular weight heparin for treatment of acute myocardial infarction (FAMI): Fragmin (dalteparin sodium) in acute myocardial infarction.

    PubMed

    Kakkar, V V; Iyengar, S S; De Lorenzo, F; Hargreaves, J R; Kadziola, Z A

    2000-01-01

    The benefit of using subcutaneous low molecular weight heparin for the treatment of acute myocardial infarction is not known. The aim of this study was to determine the efficacy of a low molecular weight heparin (dalteparin sodium) for the treatment of acute myocardial infarction in patients not treated with thrombolytic therapy. Twenty-nine cardiological centres from leading hospitals in India participated in this prospective, multicentre, double-blind, placebo-controlled study in two phases which included 1128 patients with acute myocardial infarction. In the acute phase (between day 1 and 3 of admission) all the patients received a weight-adjusted dose of subcutaneous dalteparin (120 IU/kg twice daily). In the second, double-blind phase of acute myocardial infarction, patients were randomised to receive a fixed dose of dalteparin (7,500 IU) or an identical placebo injection for 30 days. A composite primary endpoint of death, reinfarction, recurrence of angina and emergency revascularisation was used. All the 1128 patients with acute myocardial infarction were included in the trial. In the acute phase, the composite primary endpoint was observed in 58 (5.1%) patients. Of 1037 paients who were randomly assigned to receive a fixed dose of dalteparin (n=519) or placebo (n=518), the composite primary event rate was 6.7 percent and 7.0 percent, respectively (RR 0.97; 95% CI 0.62-1.52; p=0.90). To conclude, treatment with dalteparin administered subcutaneously in a weight-adjusted dose of 120 IU/kg twice daily resulted in a lower than expected mortality during the acute phase of myocardial infarction. A lower fixed once daily dose of 7,500 IU during the chronic phase did not confer additional protection.

  7. Fluoxetine effects assessment on the life cycle of aquatic invertebrates.

    PubMed

    Péry, A R R; Gust, M; Vollat, B; Mons, R; Ramil, M; Fink, G; Ternes, T; Garric, J

    2008-09-01

    Fluoxetine is a serotonin re-uptake inhibitor, generally used as an antidepressant. It is suspected to provoke substantial effects in the aquatic environment. This study reports the effects of fluoxetine on the life cycle of four invertebrate species, Daphnia magna, Hyalella azteca and the snail Potamopyrgus antipodarum exposed to fluoxetine spiked-water and the midge Chironomus riparius exposed to fluoxetine-spiked sediments. For D. magna, a multi-generational study was performed with exposition of newborns from exposed organisms. Effects of fluoxetine could be found at low measured concentrations (around 10microgl(-1)), especially for parthenogenetic reproduction of D. magna and P. antipodarum. For daphnids, newborns length was impacted by fluoxetine and the second generation of exposed individuals showed much more pronounced effects than the first one, with a NOEC of 8.9microgl(-1). For P. antipodarum, significant decrease of reproduction was found for concentrations around 10microgl(-1). In contrast, we found no effect on the reproduction of H. azteca but a significant effect on growth, which resulted in a NOEC of 33microgl(-1), expressed in nominal concentration. No effect on C. riparius could be found for measured concentrations up to 59.5mgkg(-1). General mechanistic energy-based models showed poor relevance for data analysis, which suggests that fluoxetine targets specific mechanisms of reproduction.

  8. Protective Effects of Fluoxetine on Decompression Sickness in Mice

    PubMed Central

    Blatteau, Jean-Eric; Barre, Sandrine; Pascual, Aurelie; Castagna, Olivier; Abraini, Jacques H.; Risso, Jean-Jacques; Vallee, Nicolas

    2012-01-01

    Massive bubble formation after diving can lead to decompression sickness (DCS) that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46) while controls were not treated (n = 45). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004). Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes. PMID:23145072

  9. Direct inhibition of retinoic acid catabolism by fluoxetine.

    PubMed

    Hellmann-Regen, Julian; Uhlemann, Ria; Regen, Francesca; Heuser, Isabella; Otte, Christian; Endres, Matthias; Gertz, Karen; Kronenberg, Golo

    2015-09-01

    Recent evidence from animal and human studies suggests neuroprotective effects of the SSRI fluoxetine, e.g., in the aftermath of stroke. The underlying molecular mechanisms remain to be fully defined. Because of its effects on the cytochrome P450 system (CYP450), we hypothesized that neuroprotection by fluoxetine is related to altered metabolism of retinoic acid (RA), whose CYP450-mediated degradation in brain tissue constitutes an important step in the regulation of its site-specific auto- and paracrine actions. Using traditional pharmacological in vitro assays, the effects of fluoxetine on RA degradation were probed in crude synaptosomes from rat brain and human-derived SH-SY5Y cells, and in cultures of neuron-like SH-SY5Y cells. Furthermore, retinoid-dependent effects of fluoxetine on neuronal survival following glutamate exposure were investigated in rat primary neurons cells using specific retinoid receptor antagonists. Experiments revealed dose-dependent inhibition of synaptosomal RA degradation by fluoxetine along with dose-dependent increases in RA levels in cell cultures. Furthermore, fluoxetine's neuroprotective effects against glutamate excitotoxicity in rat primary neurons were demonstrated to partially depend on RA signaling. Taken together, these findings demonstrate for the first time that the potent, pleiotropic antidepressant fluoxetine directly interacts with RA homeostasis in brain tissue, thereby exerting its neuroprotective effects.

  10. Use of medications in the treatment of acute low back pain.

    PubMed

    Malanga, Gerard A; Dennis, Robin L

    2006-01-01

    The prescription of medications continues to be one of the mainstays of treatment of acute low back pain episodes. The goals of the pharmacologic treatment for acute low back are reduction of pain and return of normal function. Often, nociception is a result of secondary inflammation and muscle spasm after acute injury of a structure of the spine, which may include muscle, tendon, ligament, disc, or bone. An understanding of the appropriate use of medications to address the underlying pain generator and the current evidence for using these medications is essential for any physician who sees and treats patients with acute low back pain.

  11. 75 FR 32490 - Issues in the Development of Medical Products for the Prophylaxis and/or Treatment of Acute...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... Prophylaxis and/or Treatment of Acute Antibody Mediated Rejection in Kidney Transplant Recipients; Public... prophylaxis and/or treatment of acute antibody mediated rejection (AMR) in kidney transplant recipients....

  12. Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry.

    PubMed

    Kalia, M; O'Callaghan, J P; Miller, D B; Kramer, M

    2000-03-06

    We compared the effects of treatment with high doses of fluoxetine, sibutramine, sertraline, and dexfenfluramine for 4 days on brain serotonergic nerve terminals in rats. Methylenedioxymethamphetamine (MDMA) and 5,7-dihydroxytryptamine (5,7-DHT) were used as positive controls because both compounds deplete brain serotonin. Food intake and body weight changes were also monitored and yoked, pair-fed animals were used to control for possible changes in morphology due to nutritional deficits. Fluoxetine, sibutramine, sertraline and dexfenfluramine all produced a significant reduction in body weight. Fluoxetine, sibutramine and sertraline treatment resulted in no depletion of brain serotonin but produced morphological abnormalities in the serotonergic immunoreactive nerve network. In contrast, dexfenfluramine and MDMA depleted brain serotonin and produced morphological changes in the serotonin nerve network. These results indicate that even though fluoxetine, sibutramine and sertraline do not deplete brain serotonin, they do produce morphological changes in several brain regions (as identified by serotonin immunohistochemistry). Dexfenfluramine and MDMA, on the other hand, markedly deplete brain serotonin and also produce morphological changes. Collectively, these results lend support to the concept that all compounds acting on brain serotonin systems, whether capable of producing serotonin depletion or not, could produce similar effects on the morphology of cerebral serotonin systems.

  13. Technologies for diagnosis and treatment of acute stroke

    SciTech Connect

    Fitch, J.P.

    1998-02-09

    From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expected as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.

  14. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis

    PubMed Central

    Shelton, Celeste A.; Whitcomb, David C.

    2014-01-01

    Opinion Statement Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants – including a new class of bicarbonate-defective mutations – and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management. PMID:24954874

  15. Basic mechanisms of migraine and its acute treatment.

    PubMed

    Edvinsson, Lars; Villalón, Carlos M; MaassenVanDenBrink, Antoinette

    2012-12-01

    Migraine is a neurovascular disorder characterized by recurrent unilateral headaches accompanied by nausea, vomiting, photophobia and phonophobia. Current theories suggest that the initiation of a migraine attack involves a primary event in the central nervous system (CNS), probably involving a combination of genetic changes in ion channels and environmental changes, which renders the individual more sensitive to environmental factors; this may, in turn, result in a wave of cortical spreading depression (CSD) when the attack is initiated. Genetically, migraine is a complex familial disorder in which the severity and the susceptibility of individuals are most likely governed by several genes that vary between families. Early PET studies have suggested the involvement of a migraine active region in the brainstem. Migraine headache is associated with trigeminal nerve activation and calcitonin gene-related peptide (CGRP) release from the trigeminovascular system. Administration of triptans (5-HT(1B/1D) receptor agonists) causes the headache to subside and the levels of CGRP to normalize. Moreover, administration of CGRP receptor antagonists aborts the headache. Recent immunohistochemical and pharmacological results suggest that the trigeminal system has receptors for CGRP; further, 5-HT(1B/1D) receptors, which inhibit the action of CGRP in pain transmission when activated, have been demonstrated. This offers an explanation for the treatment response. The present review provides an updated analysis of the basic mechanisms involved in the pathophysiology of migraine and the various pharmacological approaches (including 5-HT(1B/1D) receptor agonists, CGRP receptor antagonists and glutamate receptor antagonists) that have shown efficacy for the acute treatment of this disorder.

  16. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    PubMed

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD.

  17. Anxiolytic effects of fluoxetine and nicotine exposure on exploratory behavior in zebrafish

    PubMed Central

    Rhinehart, Zachariah

    2016-01-01

    Zebrafish (Danio rerio) have emerged as a popular model for studying the pharmacology and behavior of anxiety. While there have been numerous studies documenting the anxiolytic and anxiogenic effects of common drugs in zebrafish, many do not report or test for behavioral differences between the sexes. Previous studies have indicated that males and females differ in their baseline level of anxiety. In this study, we test for a sex interaction with fluoxetine and nicotine. We exposed fish to system water (control), 10 mg/L fluoxetine, or 1 mg/L nicotine for three minutes prior to being subjected to four minutes in an open-field drop test. Video recordings were tracked using ProAnalyst. Fish from both drug treatments reduced swimming speed, increased vertical position, and increased use of the top half of the open field when compared with the control, though fluoxetine had a larger effect on depth related behaviors while nicotine mostly affected swimming speed. A significant sex effect was observed where females swam at a slower and more constant speed than males, however neither drug produced a sex-dependent response. PMID:27635325

  18. Preventing the co-prescription of tamoxifen and fluoxetine in General Practice.

    PubMed

    Stonier, Thomas; Harrison, Michael

    2013-01-01

    In 2010 a population-based cohort study showed that there was decreased efficacy of the breast cancer drug tamoxifen when used in combination with fluoxetine, a commonly used SSRI antidepressant. The aim of this project was to identify patients who may be affected by this co-prescription and suggest a change in medication. The project was conducted across two GP practices in Clevedon (The Riverside Practice & The Green Practice), Bristol. The patients were all from the active patients register at each surgery. A search was conducted to find all those on tamoxifen and fluoxetine, using the EMIS computer system. These patients would then be sent a letter to attend clinic. The new data would then be discussed with them before recommending a change of antidepressant (typically to sertraline). Three patients were found to be on both medications. They were all called into clinic and changed from fluoxetine to sertraline. Furthermore a presentation was given to all GPs at the two surgeries alerting them to the new guidelines. A message was also set up to flash on the computer system whenever an attempt was made to co-prescribe the two drugs. All the patients on tamoxifen in these two practices are now receiving the optimum treatment. Furthermore interventions have been put in place to ensure that this remains the case in future. Another data collection should be conducted in one year. This project provides a good example of how this problem could be resolved at other GP surgeries.

  19. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    PubMed

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

  20. Brain endocannabinoid system is involved in fluoxetine-induced anorexia.

    PubMed

    Zarate, Jon; Churruca, Itziar; Pascual, Jesús; Casis, Luis; Sallés, Joan; Echevarría, Enrique

    2008-06-01

    In order to describe the effects of chronic fluoxetine administration on the brain endocannabinoid system in lean and obese Zucker rats, brain immunostaining for the CB1 and CB1-phosphorylated cannabinoid receptors was carried out. Obese Zucker rats showed significantly increased the numbers of neural cells positively immunostained for the CB1-phosphorylated receptor in the striatum, compared to their lean litter-mates. Chronic fluoxetine administration decreased the number of neural cells immunostained for CB1-phosphorylated receptor in several striatal and hippocampal regions of obese Zucker rats, compared to controls treated with saline. In contrast, no change in CB1-phosphorylated receptor immunostaining was observed in fluoxetine-treated lean rats, with respect to controls. Taken together, these results suggest the involvement of the hippocampal and striatal endocannabinoid receptor system in fluoxetine-induced anorexia in lean and obese Zucker rats.

  1. Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

    PubMed

    Uzbay, Tayfun; Kayir, Hakan; Celik, Turgay; Yüksel, Nevzat

    2006-05-01

    Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

  2. Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

    PubMed Central

    Huang, Guo-Jen; Ben-David, Eyal; Tort Piella, Agnès; Edwards, Andrew; Flint, Jonathan; Shifman, Sagiv

    2012-01-01

    Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy. PMID:22558262

  3. Neurogenomic evidence for a shared mechanism of the antidepressant effects of exercise and chronic fluoxetine in mice.

    PubMed

    Huang, Guo-Jen; Ben-David, Eyal; Tort Piella, Agnès; Edwards, Andrew; Flint, Jonathan; Shifman, Sagiv

    2012-01-01

    Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug--fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy.

  4. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

    PubMed

    DeLong, G Robert; Ritch, Chad R; Burch, Sherri

    2002-10-01

    One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

  5. Fluoxetine regulates cell growth inhibition of interferon-α.

    PubMed

    Lin, Yu-Min; Yu, Bu-Chin; Chiu, Wen-Tai; Sun, Hung-Yu; Chien, Yu-Chieh; Su, Hui-Chen; Yen, Shu-Yang; Lai, Hsin-Wen; Bai, Chyi-Huey; Young, Kung-Chia; Tsao, Chiung-Wen

    2016-10-01

    Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

  6. Midostaurin: an emerging treatment for acute myeloid leukemia patients

    PubMed Central

    Gallogly, Molly Megan; Lazarus, Hillard M

    2016-01-01

    Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin’s ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are

  7. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  8. Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague-Dawley rat offspring.

    PubMed

    Knaepen, Liesbeth; Rayen, Ine; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; van Kleef, Maarten; Steinbusch, Harry W; Patijn, Jacob; Tibboel, Dick; Joosten, Elbert A; Pawluski, Jodi L

    2013-01-01

    Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system.

  9. Prelimbic cortex 5-HT1A and 5-HT2C receptors are involved in the hypophagic effects caused by fluoxetine in fasted rats.

    PubMed

    Stanquini, Laura A; Resstel, Leonardo B M; Corrêa, Fernando M A; Joca, Sâmia R L; Scopinho, América A

    2015-09-01

    The regulation of food intake involves a complex interplay between the central nervous system and the activity of organs involved in energy homeostasis. Besides the hypothalamus, recognized as the center of this regulation, other structures are involved, especially limbic regions such as the ventral medial prefrontal cortex (vMPFC). Monoamines, such as serotonin (5-HT), play an important role in appetite regulation. However, the effect in the vMPFC of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on food intake has not been studied. The aim of the present study was to study the effects on food intake of fed and fasted rats evoked by fluoxetine injection into the prelimbic cortex (PL), a sub-region of the vMPFC, or given systemically, and which 5-HT receptors in the PL are involved in fluoxetine responses. Fluoxetine was injected into the PL or given systemically in male Wistar rats. Independent groups of rats were pretreated with intra-PL antagonists of 5-HT receptors: 5-HT1A (WAY100635), 5-HT2C (SB242084) or 5-HT1B (SB216641). Fluoxetine (0.1; 1; 3; 10nmol/200nL) injected into the PL induced a dose-dependent hypophagic effect in fasted rats. This effect was reversed by prior local treatment with WAY100635 (1; 10nmol) or SB242084 (1; 10nmol), but not with SB216641 (0.2; 2.5; 10nmol). Systemic fluoxetine induced a hypophagic effect, which was blocked by intra-PL 5-HT2C antagonist (10nmol) administration. Our findings suggest that PL 5-HT neurotransmission modulates the central control of food intake and 5-HT1A and 5-HT2C receptors in the PL could be potential targets for the action of fluoxetine.

  10. Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor.

    PubMed

    Van Waes, Vincent; Ehrlich, Sarah; Beverley, Joel A; Steiner, Heinz

    2015-02-01

    Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling.

  11. Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area in rats.

    PubMed

    Luo, Pan; Zhang, Xiaoxue; Lu, Yun; Chen, Cheng; Li, Changjun; Zhou, Mei; Lu, Qing; Xu, Xulin; Shen, Guanxin; Guo, Lianjun

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Two weeks later, rats were treated with 30 mg/kg fluoxetine (intragastric injection, i.g.) for 6 weeks. Cognitive function was evaluated by Morris water maze (MWM) and novel objects recognition (NOR) test. Long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Western blotting was used to quantify the protein levels. Our results showed that fluoxetine treatment significantly improved the cognitive impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, 2VO caused an up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 surface expressions, which may be a possible mechanism that fluoxetine treatment ameliorates cognitive impairments in rats with CCH.

  12. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-26

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy.

  13. Oncostatic effects of fluoxetine in experimental colon cancer models.

    PubMed

    Kannen, Vinicius; Garcia, Sergio Britto; Silva, Wilson A; Gasser, Martin; Mönch, Romana; Alho, Eduardo Joaquim Lopes; Heinsen, Helmut; Scholz, Claus-Jürgen; Friedrich, Mike; Heinze, Katrin Gertrud; Waaga-Gasser, Ana Maria; Stopper, Helga

    2015-09-01

    Colon cancer is one of the most common tumors in the human population. Recent studies have shown a reduced risk for colon cancer in patients given the antidepressant fluoxetine (FLX). The exact mechanism by which FLX might protect from colon cancer remains however controversial. Here, FLX reduced the development of different colon tumor xenografts, as well as proliferation in hypoxic tumor areas within them. FLX treatment also decreased microvessel numbers in tumors. Although FLX did not increase serum and tumor glucose levels as much as the colon chemotherapy gold standard Fluorouracil did, lactate levels were significantly augmented within tumors by FLX treatment. The gene expression of the MCT4 lactate transporter was significantly downregulated. Total protein amounts from the third and fifth mitochondrial complexes were significantly decreased by FLX in tumors. Cell culture experiments revealed that FLX reduced the mitochondrial membrane potential significantly and disabled the reactive oxygen species production of the third mitochondrial complex. Furthermore, FLX arrested hypoxic colon tumor cells in the G0/G1 phase of the cell-cycle. The expression of key cell-cycle-related checkpoint proteins was enhanced in cell culture and in vivo experiments. Therefore, we suggest FLX impairs energy generation, cell cycle progression and proliferation in tumor cells, especially under condition of hypoxia. This then leads to reduced microvessel formation and tumor shrinkage in xenograft models.

  14. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  15. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  16. Successful treatment of acute systemic anaphylaxis in a western lowland gorilla (Gorilla gorilla gorilla).

    PubMed

    Hayman, David T S; King, Tony; Cameron, Kenneth

    2010-09-01

    This brief communication describes the successful treatment of acute systemic anaphylaxis in a wild-born but captive infant western lowland gorilla (Gorilla gorilla gorilla) in the Republic of Congo. The infant demonstrated signs of acute respiratory distress, lingual swelling, and reaction to intradermal tuberculin, given 55 hr earlier. Details of the treatment with steroids, anesthetic induction, and i.v. epinephrine are all reported, and potential antigens that may have initiated the anaphylactic shock are discussed.

  17. Treatment of angular deformities of the tibia in children: acute versus gradual correction.

    PubMed

    McCarthy, James J; Mark, Arthur K; Davidson, Richard S

    2007-01-01

    This is a retrospective review of 25 tibial osteotomies (in 19 patients) performed with either acute or gradual correction to determine the outcome of treatment and incidence of neurovascular complications. Patients undergoing gradual correction had fewer neurovascular complications and greater correction than those undergoing acute correction (27 degrees vs. 18 degrees, respectively). It was concluded that gradual correction tends to be a safer technique for the treatment of tibial deformities and allows greater correction.

  18. The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression.

    PubMed

    Rahn, K A; Cao, Y-J; Hendrix, C W; Kaplin, A I

    2015-05-05

    Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed.

  19. [Prevention and treatment of acute diarrhea in infants].

    PubMed

    Turck, D

    2007-11-01

    The prognosis of acute diarrhoea in infants is most often satisfactory in industrialized countries. However, it has been estimated that 10 to 15 children die every year in France from acute dehydration due to acute diarrhoea. In spite of an increasing use over the least few years, oral rehydration solutions (ORS) are used in only 70% of infants presenting with acute diarrhoea. The use of homemade ORS, plain water or fizzy drink should be strictly avoided. In case of acute diarrhoea there is no indication to stop breastfeeding or the use of infant formula for more than 4 hours. Lactose intolerance is observed in only 5-10% of infants. Lactose free formulae should only be used in infants with severe, persistent or recurrent diarrhoea. Under 3-4 months of age, infants with severe diarrhoea should receive for a period of 2-4 weeks lactose free protein hydrolysate formulae. Racecadotril is the only drug with anti-diarrheal properties, with a reduction of the stool output of 50%. Oral antibiotics should only be used in case of Shigella infection or in case of bacterial infection with severe sepsis or underlying debilitating disease. Oral Rotavirus vaccine, that is not reimbursed yet in France, has been shown to dramatically reduce the number of severe cases of diarrhoea with dehydration, and has been associated with a striking reduction of both morbidity and mortality, as well as of the number of hospitalisations during periods of epidemics.

  20. [Cardiogenic shock in acute myocardial infarct. Its coronary angioplasty treatment].

    PubMed

    Fernández Valadez, E; García y Otero, J M; Escobar, G P; Frutos Rangel, E; Zúñiga Sedano, J; García García, R; Verduzco Bazavilvazo, S; López Aranda, J; López Ruiz, J

    1993-01-01

    Ventricular dysfunction is the most common cause of in-hospital death in patients with acute myocardial infarction. When cardiogenic shock is manifested the mortality is very high. Seven patients with cardiogenic shock complicating acute myocardial infarction were treated with emergency coronary angioplasty. Four patients required cardiopulmonary resuscitation (CPR), 2 intraaortic balloon pump support and one femoro-femoral bypass pump support during the coronary angioplasty. The angiography success rate was 86%. Two patients died, one in the catheterization laboratory and the other one 24 hours later. The hospital mortality was 29%. Of the patients who survived 4 are in functional class I and one in functional class II (NYHA). Coronary angioplasty therapy in patients with cardiogenic shock complicating acute myocardial infarction plays a decisive role in the reduction of mortality.

  1. Acute promyelocytic leukemia: new issues on pathogenesis and treatment response.

    PubMed

    Vitoux, Dominique; Nasr, Rihab; de The, Hugues

    2007-01-01

    Pathogenesis of acute promyelocytic leukemia appears to be one of the best understood among human malignancies. The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. A set of recent data has significantly increased the complexity of our view of acute promyelocytic leukemia pathogenesis, as well as of therapeutic response. This review summarizes and discusses these findings, which yield novels questions and models.

  2. Early Treatment of Severe Acute Respiratory Distress Syndrome.

    PubMed

    Przybysz, Thomas M; Heffner, Alan C

    2016-02-01

    Acute respiratory distress syndrome (ARDS) is defined by acute diffuse inflammatory lung injury invoked by a variety of systemic or pulmonary insults. Despite medical progress in management, mortality remains 27% to 45%. Patients with ARDS should be managed with low tidal volume ventilation. Permissive hypercapnea is well tolerated. Conservative fluid strategy can reduce ventilator and hospital days in patients without shock. Prone positioning and neuromuscular blockers reduce mortality in some patients. Early management of ARDS is relevant to emergency medicine. Identifying ARDS patients who should be transferred to an extracorporeal membrane oxygenation center is an important task for emergency providers.

  3. Pulmonary oedema during treatment of acute water intoxication.

    PubMed Central

    Maclean, D.; Champion, M.; Trash, D. B.

    1976-01-01

    Acute water intoxication with deepening coma and uncontrolled epileptiform seizures in a 25-year-old previously fit male schizophrenic was treated with hypertonic (2 N) saline and a 20% mannitol solution. This improved his neurological state but precipitated severe pulmonary oedema. Intravenous frusemide increased his urinary output sufficiently to clear the pulmonary oedema. In acute water intoxication the use of hypertonic solutions may thus precipitate left heart failure by expanding the intra-pulmonary blood volume beyond the capacity of even a healthy left ventricle to compensate. Simple water restriction will produce a slower but perhaps safer improvement. Images Fig. 1 PMID:981097

  4. Acute Dystonia After Single Dose of Bupropion

    PubMed Central

    Elyasi, Forouzan; Mahtiyan, Elham

    2016-01-01

    Bupropion is an antidepressant that is effective in the treatment of major depressive disorders, smoking cessation, and sexual side effects of selective serotonin reuptake inhibitors. Acute dystonia is characterized by prolonged muscle contraction often represented by spasms of the head and neck muscles as well as occasional jaw clenching and temporomandibular joint syndrome. Although it is believed that dystonia is the result of an abnormality of the basal ganglia, its pathophysiology is still unclear. A few cases of dystonia resulting from bupropion have been reported in prior research papers. This case report discusses a patient who had a neck spasm painful enough to wake him up and dystonic distortion after taking only one dose of 75 mg bupropion. The patient was a young 34-year-old man with a diagnosis of obsessive-compulsive disorder treated with 60 mg fluoxetine. Bupropion was added to his medications because of sexual side effects caused by the fluoxetine. It seems that we must be careful to watch for dystonic symptoms when bupropion is mixed with other drugs that affect serotonin reuptake. Although dystonia is a rare side effect of bupropion, physicians should be aware of it and manage it if it occurs. PMID:27833231

  5. [Guideline on diagnosis and treatment of acute appendicitis: imaging prior to appendectomy is recommended].

    PubMed

    Bakker, Olaf J; Go, Peter M N Y H; Puylaert, Julien B C M; Kazemier, Geert; Heij, Hugo A

    2010-01-01

    Every year, over 2500 unnecessary appendectomies are carried out in the Netherlands. At the initiative of the Dutch College of Surgeons, the evidence-based guideline on the diagnosis and treatment of acute appendicitis was developed. This guideline recommends that appendectomy should not be carried out without prior imaging. Ultrasonography is the recommended imaging technique in patients with suspected appendicitis. After negative or inconclusive ultrasonography, a CT scan can be carried out. Appendectomy is the standard treatment for acute appendicitis; this can be done either by open or laparoscopic surgery. The first choice treatment of appendicular infiltrate is conservative treatment.

  6. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care.

  7. Aggressive Early Debridement in Treatment of Acute Periprosthetic Joint Infections After Hip and Knee Replacements

    PubMed Central

    Volpin, Andrea; Sukeik, Mohamed; Alazzawi, Sulaiman; Haddad, Fares Sami

    2016-01-01

    Background: Periprosthetic Joint Infection Remains a Dreaded Complication After Hip and Knee Replacement Surgery. Treatment Options for Acute Postoperative and Acute Hematogenous Infections Include Arthroscopic or Open Debridement With Retention or Exchange of the Prostheses. This Review Article Aims to Summarize the Evidence for Management of Acute Postoperative And Acute Hematogenous Infections. Methods: A Systematic Literature Search Was Performed Using a Computer-based Search Engine Covering Medline (OvidSP), PubMed Database (U.S. National Library of Medicine, National Institutes of Health), Embase, Web of Science, Cochrane and Google Scholar for Relevant Articles. Results: Common Themes Around Treatment of Acute Postoperative and Acute Hematogenous Infections Discussed in this Review Include the Timing of Intervention, Description of the Optimal Procedure and How we Perform it at our Institution, the Role of Arthroscopic Debridement, Most Commonly Isolated Micro-organisms and Prognostic Factors for Infection Control. Conclusion: Success in Treating Acute Postoperative and Acute Hematogenous Infections Depends on Early Diagnosis and Aggressive Surgical Debridement Combined With Effective Antibiotic Therapy. PMID:28144377

  8. [Treatment of acute porphyrias. The importance of follow-up of patients and carriers].

    PubMed

    Tasnádi, Gyöngyi; Bor, Márta; Pusztai, Agnes

    2003-05-11

    Acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types of them: acute intermittent porphyria, porphyria variegata, coproporphyria and delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of their frequency. Basically the clinical picture is the same in the four types of acute porphyria. The most frequent complaints and symptoms are: cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the advanced phase, there is a red-colored urine, hyponatremia, subileus, acute psychosis and Landry-type paralysis. Without proper treatment death is caused by respiratory paralysis or serious arrhythmia. In case of suspicion of acute porphyria it is mandatory to identify the type of the acute porphyria and the actual status of the patient. The later indicates what kind of treatment should be used. In the acute phase the early therapy with heme arginate is the treatment of choice. Since the clinical symptoms are precipitated by endogenous or exogenous inducing factors--most often by drugs-, the drugs negatively affecting the heme biosynthesis should be omitted at once even in the suspicion of acute porphyria. The role of the inducing factors in the manifestation of the clinical symptoms makes possible the prevention. It is possible to avoid the inducing factors and this way to prevent the acute attack if the acute porphyrias are recognized in time and the patients and the carriers are under regular control. The patients receive special identification card and the up-to-date list of safe drugs. They can use only these drugs in any kind of illness. Other drugs should be considered as porphyrinogenic since it is impossible to predict based on their chemical structure if they negatively affect the heme biosynthesis.

  9. Assessment and treatment of patients with acute tachyarrhythmia.

    PubMed

    Swift, Jennie

    A tachyarrhythmia is defined as a heart rate greater than 100 beats per minute in conjunction with abnormal cardiac conduction. This article aims to inform nurses and other healthcare professionals about the predominant acute tachyarrhythmias. It focuses on the assessment and management of patients with this condition using case study examples.

  10. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  11. Visual prognosis following treatment of acute central retinal artery obstruction.

    PubMed Central

    Augsburger, J J; Magargal, L E

    1980-01-01

    The authors report the visual outcome in 34 consecutive cases of treated acute central retinal artery obstruction. Visual acuity equal to or better than 6/30 was recovered in 35% of the cases. The presenting visual acuity and duration of visual impairment appear to correlate with visual prognosis. PMID:7448144

  12. Optimizing the Treatment of Acute Duct-Destructive Pancreatitis

    ERIC Educational Resources Information Center

    Zhakiev, Bazylbek S.; Karsakbayev, Uteugali G.; Kelimberdiev, Mersaid S.; ?uhamedgalieva, Bodagoz M.; K?nonenko, Aleksander F.

    2016-01-01

    The search for new methods for treating duct-destructive pancreatitis is a relevant problem. Endogenous intoxication and oxidative stress that accompany acute pancreatitis often progress even after surgery, which forces one to search for additional possibilities of preventing these severe consequences. This research studied the effect of small…

  13. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  14. Acute myocardial infarction in a young woman on isotretinoin treatment.

    PubMed

    Lorenzo, Natalia; Antuña, Paula; Dominguez, Lourdes; Rivero, Fernando; Bastante, Teresa; Alfonso, Fernando

    2015-02-15

    The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion.

  15. Communication Disorders and Treatment in the Acute Trauma Center Setting.

    ERIC Educational Resources Information Center

    Schwartz-Cowley, Roberta; Stepanik, Mark J.

    1989-01-01

    The Shock Trauma Center of the Maryland Institute for Emergency Medical Services Systems instituted a comprehensive speech-language pathology program to provide acute intervention for communicative disorders in a critical/intensive care environment. This article provides a profile of the Center, a review of communicative impairments, and examples…

  16. From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

    PubMed

    Schreiber, Shaul; Pick, Chaim G

    2006-08-01

    Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.

  17. Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins.

    PubMed

    Raap, D K; Garcia, F; Muma, N A; Wolf, W A; Battaglia, G; van de Kar, L D

    1999-02-01

    Long-term exposure to fluoxetine produces a desensitization of hypothalamic postsynaptic 5-hydroxytryptamine (5-HT)1A receptors, indicated by a substantial inhibition of the 5-HT1A receptor-mediated stimulation of oxytocin and adrenocorticotropic hormone (ACTH) secretion. The present study investigated the time course and mechanism of this desensitization after discontinuation of fluoxetine administration. Male rats were injected with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days and were challenged with a 5-HT1A agonist, [8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) 50 microg/kg, s.c.] 2, 4, 7, 14, 28, or 60 days post-treatment. In control animals, 8-OH-DPAT significantly increased (approximately 15-fold) plasma levels of oxytocin and ACTH. At 2 days post-treatment, oxytocin and ACTH responses to 8-OH-DPAT were reduced by 74% and 68%, respectively. During further withdrawal from fluoxetine, there was a gradual increase in the oxytocin response toward control levels. However, even 60 days after discontinuation of fluoxetine, the oxytocin response was still significantly reduced by 26% compared with controls. In contrast, the suppressed ACTH response to 8-OH-DPAT (a less-sensitive indicator of desensitization) gradually returned to control levels by day 14 of withdrawal from fluoxetine. Interestingly, the sustained reductions in the hormone responses occurred in the absence of reductions in Gz or Gi protein levels in the hypothalamus. Furthermore, this desensitization was sustained in the absence of detectable levels of fluoxetine and norfluoxetine in plasma and brain tissue. These findings suggest that the sustained desensitization of hypothalamic 5-HT1A receptor systems, observed during fluoxetine withdrawal, may be due to altered interactions among the protein components of the 5-HT1A receptor system, rather than their absolute levels.

  18. Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae.

    PubMed

    Johnson, David J; Sanderson, Hans; Brain, Richard A; Wilson, Christian J; Solomon, Keith R

    2007-05-01

    The toxicity of SSRIs to algae/phytoplankton was investigated using the US EPA ECOSAR, acute single-species growth inhibition assays, species sensitivity distributions (SSDs), and an outdoor microcosm mixture experiment. Worst-case ECOSAR estimates of SSRI toxicity to algae ranged from 0.73 to 13.08 mg/L. Sertraline was the most toxic SSRI tested in single-species growth inhibition assays followed by fluoxetine and fluvoxamine with worst-case 96-h IC10s of 4.6, 31.3, and 1662 microg/L, respectively. HC5s of 2.4, 3.6, and 1100 microg/L were estimated, respectively, for sertraline, fluoxetine, and fluvoxamine toxicity to algae-using SSDs. Microcosm phytoplankton structural endpoints were more sensitive than functional endpoints in the short term. However, in the long term, structural endpoints were resilient and functional endpoints remained impacted even after a period of recovery. The worst-case EC10 determined from the outdoor microcosm mixture toxicity to phytoplankton communities was 15.2 nM. Although SSRIs are toxic to algae, hazard quotients using worst-case PECs represent a margin of safety of 20 to phytoplankton. Although SSRIs do not appear to pose a hazard to primary production, this assessment is not protective of higher aquatic organisms and further research into the chronic toxicity to low levels of SSRIs to higher-level aquatic species is recommended.

  19. Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells.

    PubMed

    Zeng, Bingqing; Li, Yiwen; Niu, Bo; Wang, Xinyi; Cheng, Yufang; Zhou, Zhongzhen; You, Tingting; Liu, Yonggang; Wang, Haitao; Xu, Jiangping

    2016-08-01

    The selective serotonin reuptake inhibitor fluoxetine is neuroprotective in several brain injury models. It is commonly used to treat major depressive disorder and related conditions, but its mechanism of action remains incompletely understood. Activation of the phosphatidylinositol-3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FoxO3a) and protein kinase A/cAMP-response element binding protein (PKA/CREB) signaling pathways has been strongly implicated in the pathogenesis of depression and might be the downstream target of fluoxetine. Here, we used PC12 cells exposed to corticosterone (CORT) to study the neuroprotective effects of fluoxetine and the involvement of the PI3K/Akt/FoxO3a and PKA/CREB signaling pathways. Our results show that CORT reduced PC12 cells viability by 70 %, and that fluoxetine showed a concentration-dependent neuroprotective effect. Neuroprotective effects of fluoxetine were abolished by inhibition of PI3K, Akt, and PKA using LY294002, KRX-0401, and H89, respectively. Treatment of PC12 cells with fluoxetine resulted in increased phosphorylation of Akt, FoxO3a, and CREB. Fluoxetine also dose-dependently rescued the phosphorylation levels of Akt, FoxO3a, and CREB, following administration of CORT (from 99 to 110, 56 to 170, 80 to 170 %, respectively). In addition, inhibition of PKA and PI3K/Akt resulted in decreased levels of p-CREB, p-Akt, and p-FoxO3a in the presence of fluoxetine. Furthermore, fluoxetine reversed CORT-induced upregulation of p53-upregulated modulator of apoptosis (Puma) and Bcl-2-interacting mediator of cell death (Bim) via the PI3K/Akt/FoxO3a signaling pathway. H89 treatment reversed the effect of fluoxetine on the mRNA level of brain-derived neurotrophic factor, which was decreased in the presence of CORT. Our data indicate that fluoxetine elicited neuroprotection toward CORT-induced cell death that involves dual regulation from PI3K/Akt/FoxO3a and PKA/CREB pathways.

  20. Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress.

    PubMed

    Gomez, Francisca; García-García, Luis

    2017-02-01

    Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d-4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FLX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (≈40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FLX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FLX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FLX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of ≈2.5% after 24h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naïve rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FLX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output

  1. CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline.

    PubMed

    Alfaro, C L; Lam, Y W; Simpson, J; Ereshefsky, L

    1999-04-01

    The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective rerotonin re-uptake inhibitors (SSRIs). Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DX(BL)) and after (DM/DX(SSRI)) were compared within and between the four SSRI groups. DM/DX(BL) ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DX(BL) and DM/DX(SSRI) were found for the fluoxetine (p < 0.001; ratio values, 0.020 vs. 0.364) and paroxetine (p = 0.0005, ratio values 0.029 vs. 1.085) but not for the fluvoxamine or sertraline groups. Comparing between groups, significant differences in DM/DX(SSRI) ratios were found for fluoxetine versus sertraline (p = 0.0019, DM/DX = 0.364 vs. 0.057), fluoxetine versus fluvoxamine (p < 0.0001, DM/DX = 0.364 vs. 0.019), paroxetine versus sertraline (p = 0.0026, DM/DX = 1.085 vs. 0.057), and paroxetine versus fluvoxamine (p < 0.0001, DM/DX = 1.085 vs. 0.019). No significant differences were noted between the two potent CYP2D6 inhibitors, fluoxetine and paroxetine, or the two weakest inhibitors, fluvoxamine and sertraline. Five subjects in the fluoxetine and four subjects in the paroxetine groups changed to poor metabolizer phenotype (DM/DX > or = 0.3) after treatment. Although CYP2D6 inhibitory effects of fluvoxamine and sertraline did not yield significant differences from baseline, some subjects exhibited DM/DX ratio increases of 150 to 200%. One paroxetine-treated subject did not exhibit any CYP2D6 inhibition. SSRI dose and

  2. Monitoring and Treatment of Acute Kidney Injury in Children with Acute Lymphoblastic Leukemia After High Dose Methotrexate Chemotherapy

    PubMed Central

    Wang, Cong-Ping

    2016-01-01

    To investigate acute kidney injury (AKI) in children with acute lymphoblastic leukemia (ALL) who received high dose methotrexate (MTX) chemotherapy and explore the corresponding treatment. Methods 180 children who received high dose MTX chemotherapy were observed with serum MTX concentration and serum creatinine. Patients with AKI of stage 3 or poor response to conventional treatment were performed on hemodialysis and assessed the treatment outcome. Results 9 patients (5%) have appeared AKI, including 7 cases of AKI of stage 3. However, there were not any significant correlation between age, gender, serum MTX concentration and AKI, respectively. Compared with normal serum MTX concentration, the patients with high serum MTX concentration easily were developed to AKI, the MTX and serum creatinine concentration had been significantly decreased in 9 patients after hemodialysis. Conclusion AKI has appeared in some children with ALL who receive high dose MTX chemotherapy, and this may due to increase of serum MTX concentration. The monitoring of serum MTX concentration and AKI index could help to find out AKI, and even to prevent the occurrence of it. Furthermore, once AKI is present, those patients with AKI stage 3 or poor response to conventional treatment should be performed on hemodialysis treatment. PMID:28243295

  3. Depression and porphyria: Safe use of fluoxetine in a woman with learning disabilities.

    PubMed

    Beber, E; Cooper, S A

    1998-01-01

    Many antipsychotic and antidepressant drugs can precipitate life-threatening porphyric crisis in individuals with the underlying condition. However, when people with porphyria develop mental illness, they require treatment in order to maintain their quality of life. For this reason, although the condition is rare, psychiatrists need information regarding the safety profile of psychotropic drugs when used in people with porphyria. This case report describes the safe use of fluoxetine to treat depression in a woman with severe learning disabilities and porphyria, who failed to respond to non-pharmacological approaches.

  4. Hybrid Treatment of Acute Abdominal Aortic Thrombosis Presenting with Paraplegia.

    PubMed

    Azzarone, Matteo; De Troia, Alessandro; Iazzolino, Luigi; Nabulsi, Bilal; Tecchio, Tiziano

    2016-05-01

    Acute thrombotic or embolic occlusion of the abdominal aorta is a rare vascular emergency associated with high morbidity and mortality rates. Classically, the clinical presentation is a severe peripheral ischemia with bilateral leg pain as the predominant feature. Aortic occlusion presenting as an isolated acute onset of paraplegia due to spinal cord ischemia is very rare and requires improved awareness to prevent adverse outcomes associated with delayed diagnosis. We report the case of a 54-year-old man who presented with sudden paraplegia due to the thrombotic occlusion of the infrarenal aorta involving the first segment of the common iliac arteries on both sides; emergent transperitoneal aorto iliac thrombectomy combined with the endovascular iliac kissing-stent technique were performed achieving perioperative complete regression of the symptoms.

  5. Treatment of acute renal failure due to myeloma kidney.

    PubMed Central

    Bear, R A; Cole, E H; Lang, A; Johnson, M

    1980-01-01

    Severe renal insufficiency is considered to indicate a poor prognosis in patients with multiple myeloma, their reported median survival being approximately 2 months. In five consecutive patients with severe renal failure secondary to acute myeloma kidney early aggressive therapy, including chemotherapy and peritoneal dialysis, led to a significant improvement in the renal function of four; the fifth patient received a cadaveric renal transplant after 1 year of peritoneal dialysis. After a median follow-up period of 12 months all the patients were alive and had improved renal function. This experience contrasts with that previously reported and suggests that aggressive management may improve the survival of patients with acute renal failure due to myeloma kidney. PMID:7004618

  6. [Acute myocardial infarction during tocolytic treatment with ritodrine].

    PubMed

    Fornet, I; Calvo, M; Gimeno, M; Canser, E; Alonso, E; Gilsanz, F

    2006-05-01

    Ritodrine, a beta2-adrenergic agonist with a selective effect on the uterine muscle, is prescribed to prevent premature labor and to treat a hypertonic uterus. At therapeutic doses ritodrine has chronotropic and peripheral vasodilator effects. At high doses it has been related to sporadic cases of subendocardial necrosis, pulmonary edema, and death in pregnancy. We report the case of a pregnant woman who had a non-Q wave acute myocardial infarction after administration of ritodrine.

  7. Holmium:YAG laser angioplasty: treatment of acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1993-06-01

    We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

  8. Percutaneous mechanical thrombectomy for treatment of acute femoropopliteal bypass occlusion.

    PubMed

    Lichtenberg, Michael; Käunicke, Matthias; Hailer, Birgit

    2012-01-01

    Acute and subacute ischemia of the legs in acute and subacute femoropopliteal bypass occlusion is a dramatic situation that endangers the survival of the limbs, depending on the severity of the ischemia. Different therapy options like percutaneous mechanical thrombectomy procedures, which include rotational thrombectomy, have become available in recent years, in addition to local lysis and surgical thrombectomy. Surgical thrombectomy using the Fogarty catheter technique, in particular, shows an increased incidence of perioperative complications but only small technical success rates in randomized trials. On the other hand, local lysis is associated with increased costs due to resource-consuming measures, such as intensive monitoring and repeat angiographies, in addition to bleeding complications. In the past, further development of the Straub Rotarex(®) system as an endovascular therapy option has demonstrated good success leading to amputation-free survival in multiple studies. At the same time, a low rate of complications with use has been documented. Most examinations have been conducted in the thigh. To date, there are little investigational data on its use in acutely and subacutely occluded femoropopliteal bypasses. In this paper, the current study-based significance of the Rotarex system for this indication is analyzed based on the existing literature and the authors' own experiences with 22 patients.

  9. Percutaneous mechanical thrombectomy for treatment of acute femoropopliteal bypass occlusion

    PubMed Central

    Lichtenberg, Michael; Käunicke, Matthias; Hailer, Birgit

    2012-01-01

    Acute and subacute ischemia of the legs in acute and subacute femoropopliteal bypass occlusion is a dramatic situation that endangers the survival of the limbs, depending on the severity of the ischemia. Different therapy options like percutaneous mechanical thrombectomy procedures, which include rotational thrombectomy, have become available in recent years, in addition to local lysis and surgical thrombectomy. Surgical thrombectomy using the Fogarty catheter technique, in particular, shows an increased incidence of perioperative complications but only small technical success rates in randomized trials. On the other hand, local lysis is associated with increased costs due to resource-consuming measures, such as intensive monitoring and repeat angiographies, in addition to bleeding complications. In the past, further development of the Straub Rotarex® system as an endovascular therapy option has demonstrated good success leading to amputation-free survival in multiple studies. At the same time, a low rate of complications with use has been documented. Most examinations have been conducted in the thigh. To date, there are little investigational data on its use in acutely and subacutely occluded femoropopliteal bypasses. In this paper, the current study-based significance of the Rotarex system for this indication is analyzed based on the existing literature and the authors’ own experiences with 22 patients. PMID:22661895

  10. High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

    PubMed

    Jacobson, Kathleen R; Arora, Sanjay; Walsh, Kristin B; Lora, Meredith; Merjavy, Stephen; Livermore, Shanna; Menchine, Michael

    2016-07-01

    Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum.

  11. Conventional and emerging treatments in the management of acute primary angle closure

    PubMed Central

    Boey, Pui Yi; Singhal, Shweta; Perera, Shamira A; Aung, Tin

    2012-01-01

    The management of acute primary angle closure is directed at lowering the intraocular pressure and relieving pupil block. Conventional treatment involves the use of medical treatment and laser peripheral iridotomy, respectively, as a means for achieving these aims. Newer therapeutic strategies have been described that are potentially useful adjuncts or alternatives to conventional treatment. Emerging strategies that lower intraocular pressure include anterior chamber paracentesis, as well as laser procedures such as iridoplasty and pupilloplasty. A possible alternative to relieving pupil block is lens extraction, and may be combined with adjunctive measures such as goniosynechiolysis and viscogoniosynechiolysis. Trabeculectomy has a limited role in the acute setting. This review paper reviews the current evidence regarding conventional and newer treatment modalities for acute primary angle closure. PMID:22536030

  12. Treatment of acute puerperal metritis with flunixin meglumine in addition to antibiotic treatment.

    PubMed

    Drillich, M; Voigt, D; Forderung, D; Heuwieser, W

    2007-08-01

    The objective of this field trial was to evaluate effects of a single administration of 2.2 mg/kg of body weight (BW) of flunixin meglumine (FM) in addition to a systemic antibiotic treatment in cows with acute puerperal metritis (APM). Outcome variables tested were proportion of cows with a fever, prevalence of chronic endometritis 18 to 22 and 32 to 35 d in milk (DIM), and reproductive performance measures in the current lactation. In addition, serum concentrations of haptoglobin and fibrinogen were analyzed. Daily milk yield within 6 d after the first treatment was recorded. Cows were examined 4 to 5 DIM by rectal palpation and vaginoscopy, and rectal temperature was measured. Fetid vulvar discharge and a body temperature > or = 39.5 degrees C were signs of APM. Cows with APM were treated in the reference group with 1.0 mg/kg of BW of ceftiofur on 3 to 5 consecutive days (CEF, n = 119). In the study group, cows received the same antibiotic treatment as in CEF and 2.2 mg/kg of BW of FM on treatment d 1 (CEF + FM, n = 119). Blood samples were collected 4, 6, and 10 DIM and analyzed for concentrations of haptoglobin and fibrinogen. A group of cows without APM remained untreated and served as controls (n = 9). There were no significant differences between CEF and CEF + FM in the proportion of cows with fever 1 d after the first treatment (33.6 vs. 46.2%), milk yield per milking 10 DIM (7.5 +/- 0.3 vs. 7.6 +/- 0.3 kg in primiparous, 9.6 +/- 0.4 vs. 10.6 +/- 0.4 kg in multiparous cows), prevalence of chronic endometritis 32 to 35 DIM (64.3 vs. 52.2%), and in reproductive performance (31.5 vs. 34.3% conception to first AI, 58.0 vs. 54.6% pregnancy rate, 107.8 +/- 36.9 vs. 101.6 +/- 41.4 d open). Compared with the control, CEF and CEF + FM had significantly greater concentrations of haptoglobin (1.1 +/- 0.28 vs. 1.9 +/- 0.06 and 1.8 +/- 0.07 mg/mL at 4 DIM; 0.3 +/- 0.15 vs. 1.1 +/- 0.06 and 1.2 +/- 0.07 mg/mL at 10 DIM) and fibrinogen (2.2 +/- 0.17 vs. 3.9 +/- 0.14 and

  13. Effect of fluoxetine on blood concentrations of serotonin, cortisol and dehydroepiandrosterone in canine aggression.

    PubMed

    Rosado, B; García-Belenguer, S; León, M; Chacón, G; Villegas, A; Palacio, J

    2011-10-01

    Canine aggression directed towards people is the most frequent reason for referral to behaviour practices. The serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in controlling aggression. The selective serotonin reuptake inhibitor fluoxetine is the most commonly used drug in canine aggression. The aim of the present study was to assess the effect of a 30-day-long fluoxetine treatment on the peripheral serotonergic system and the HPA axis in canine aggression. To this end, the concentrations of serum serotonin (5-HT) and plasma cortisol and dehydroepiandrosterone (DHEA) were analysed in a group of aggressive (n = 22) and nonaggressive dogs (n = 9) during pre- (day 0) and posttreatment (day 30) conditions. Treatment caused a significant decrease in 5-HT concentrations (46% in the aggressive group and 32% in the control group). There was a trend towards a rise of DHEA/cortisol ratio values after treatment both in the aggressive and the control group. The determination of blood 5-HT and the DHEA/cortisol ratio could have important clinical applications in the future for deciding which animals might benefit from a given treatment as well as for monitoring the response. Further large-scale studies with this aim should be carried out to obtain sound conclusions.

  14. [Clinical practice guidelines on the diagnosis and treatment of infectious acute diarrhea in children Peru - 2011].

    PubMed

    Gonzales S, Carlos; Bada M, Carlos; Rojas G, Raúl; Bernaola A, Guillermo; Chávez B, Carlos

    2011-01-01

    The Clinical Practice Guidelines cover the Diagnosis and Treatment of Acute Diarrhea in Pediatric Infectious is a consice information about definition, inclusion and exclusion criteria; epidemiology and etiology of infectious diarrhea. The guidelines cover aspects of diagnosis and treatment (dehydration, antibiotics, supportive therapy), nutritional support and other aspects of transferences and prevention.

  15. Penicillin-induced hemolytic anemia and acute hepatic failure following treatment of tetanus in a horse.

    PubMed

    Step, D L; Blue, J T; Dill, S G

    1991-01-01

    Acute, severe hemolytic anemia occurred in a horse being treated for tetanus with intravenous penicillin and tetanus antitoxin. During treatment, the horse developed a positive direct antiglobulin test and a high titer (maximum 1:1024) of IgG anti-penicillin antibody. The horse recovered from the tetanus and penicillin induced hemolytic anemia, but later developed acute hepatic failure, probably resulting from the administration of equine origin tetanus antitoxin.

  16. A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

    PubMed

    Reinares, María; Rosa, Adriane R; Franco, Carolina; Goikolea, José Manuel; Fountoulakis, Kostas; Siamouli, Melina; Gonda, Xenia; Frangou, Sophia; Vieta, Eduard

    2013-03-01

    Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

  17. Retrievable stent thrombectomy in the treatment of acute ischemic stroke: analysis of a revolutionizing treatment technique.

    PubMed

    Walcott, Brian P; Boehm, Kevin M; Stapleton, Christopher J; Mehta, Brijesh P; Nahed, Brian V; Ogilvy, Christopher S

    2013-10-01

    Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes. We analyzed the cumulative human experience reported for the Trevo Pro Retrieval System (Stryker, Kalamazoo, MI, USA) and the Solitaire FR Revascularization Device (ev3, Irvine, CA, USA) as the definitive treatment for acute ischemic stroke. A literature search was undertaken to identify studies using the retrievable stents published up to September 2012. Nineteen studies identified a total of 576 patients treated with either the Trevo (n=221) or Solitaire (n=355) devices. Pooled data analysis identified median baseline National Institutes of Health Stroke Scale scores of 18.5 ± 0.289 (standard error of the mean) and 17.9 ± 0.610, and time to recanalization of 53.9 ± 23.6 minutes and 59.0 ± 8.0 minutes for the Trevo and Solitaire groups, respectively. Recanalization was variably defined by individual studies, most commonly achieving at least a thrombolysis in cerebral infarction score of 2a-3 or a thrombolysis in myocardial infarction score of 2-3. Revascularization (83%, 82%), mortality (31%, 14%), hemorrhage (8%, 6%), device complications (5%, 6%), and good patient outcomes (51%, 47%) were found with the Trevo and Solitaire devices, respectively. Preliminary analysis reveals excellent clinical outcomes for retrievable stent technology. This may be attributable to both high rates of revascularization with a relatively short time to perfusion restoration.

  18. Pharmacokinetics of fluoxetine in pregnant baboons (Papio spp.).

    PubMed

    Shoulson, Rivka L; Stark, Raymond L; Garland, Marianne

    2014-11-01

    Fluoxetine is used to treat a number of psychiatric conditions in humans and behavioral problems in animals. Its use in pregnancy must balance maternal benefit with potential risk to the fetus. Knowledge of adult and fetal drug disposition can assist clinicians in selecting therapy that minimizes adverse effects to the fetus. Nonhuman primate models are used frequently in drug dose-translation studies, and pregnancy in baboons has many similarities to human pregnancy. Accordingly, pharmacokinetic analysis of a series of fluoxetine and norfluoxetine administrations to pregnant baboons was performed. The mean maternal baboon steady-state clearance of fluoxetine (42 mL/min/kg) was considerably higher than that in humans. Norfluoxetine, the major active metabolite, had a higher metabolite-to-drug ratio (8.7) than that found in humans, particularly with oral dosing. These results are consistent with more extensive metabolism in baboons than in humans and leads to a higher clearance than would be expected from allometric scaling. Fetal-to-maternal fluoxetine and norfluoxetine ratios under steady-state conditions were similar to those in humans, with fetal concentrations of fluoxetine 42% and norfluoxetine 47% of maternal concentrations. The fetal clearance of fluoxetine (303 ± 176 mL/min) and norfluoxetine (450 mL/min) exceeded reported placental blood flow. Understanding these species-associated differences in metabolism is a prerequisite to extrapolating data between species. Nonetheless, nonhuman primates are likely to remain valuable models for pharmacokinetic studies during pregnancy, particularly those directed toward fetal neurodevelopmental effects. Our results also are applicable to determining appropriate dosing of nonhuman primates in clinical settings.

  19. Acute uptake inhibition increases extracellular serotonin in the rat forebrain.

    PubMed

    Rutter, J J; Auerbach, S B

    1993-06-01

    The effect of acute uptake inhibition on serotonin (5-HT) in the rat central nervous system was monitored by using in vivo dialysis. Peripheral administration of the selective 5-HT uptake blocker, fluoxetine, caused a dose-dependent increase in extracellular 5-HT in both the diencephalon and the striatum. Administration of fluoxetine or sertraline, another selective 5-HT uptake inhibitor, caused a prolonged (24 hr) increase in 5-HT and decrease in 5-hydroxyindoleacetic acid. In addition, fluoxetine and sertraline attenuated the 5-HT releasing effect of fenfluramine administered 24 hr later. Local infusion of fluoxetine into the diencephalon caused an increase in 5-HT that was twice as large as the effect of peripheral injection. Peripheral fluoxetine, by enhancing extracellular 5-HT in the raphe, probably resulted in activation of somatodendritic autoreceptors and inhibition of 5-HT neuronal discharge. Thus, the increase in 5-HT in the diencephalon after peripheral fluoxetine presumably reflected a balance between decreased release and inhibition of reuptake. In support of this, after first infusing fluoxetine into the diencephalon to maximally block reuptake, peripheral injection of the uptake inhibitor caused a decrease in 5-HT.

  20. [Efficacy and safety of mometasone furoate nasal spray in the treatment of sinusitis or acute rhinosinusitis].

    PubMed

    Klossek, J M

    2007-01-01

    Sinusitis or acute rhinosinusitis, is defined as an acute viral or bacterial infection characterised by inflammation of the mucosa of the nose and paranasal sinuses. Although antibiotics are routinely prescribed for the treatment of acute sinusitis, most cases are caused by viral infections and will resolve without antibiotic therapy. Given concerns about global antibacterial resistance, evidence-based clinical practice guidelines recommend a conservative approach to antibiotic treatment, with mild or moderately severe acute sinusitis managed symptomatically. Intranasal corticosteroids act on the nasal mucosa to relieve inflammation and its associated symptoms, and may be a useful symptomatic treatment option. Two randomised, placebo-controlled trials have demonstrated that the corticosteroid mometasone furoate, administered as a nasal spray (MFNS), is effective as an adjunct to antibiotics in acute sinusitis. The design of these studies show a therapeutic approach known in Europe, but this attitude is still different from the current French guidelines. Furthermore, the efficacy and safety of MFNS monotherapy has been compared with antibiotic therapy in a randomised, double-blind, placebo-controlled trial in adults with acute uncomplicated sinusitis and probably viral. In this study, twice-daily (BID) MFNS 200 microg produced statistically greater improvements in overall symptoms and most individual symptoms compared with amoxicillin or placebo, even though Amoxicillin is not the one recommended by the French guidelines for this indication. These findings suggest that MFNS may play an important role in the management of acute sinusitis, either as monotherapy or as adjunctive treatment to antibiotics. These results lead also to think over its interest in the treatment of uncomplicated common forms of sinusitis, where antibiotics are still widely prescribed in daily practice.

  1. Determination of fluoxetine in human plasma using reserved phase HPLC.

    PubMed

    Misztal, G; Hopkała, H

    1997-11-01

    A rapid, simple, accurate method for the determination of fluoxetine in human plasma is presented. Liquid-liquid extraction of fluoxetine was carried out using diethyl ether. Chlorprothixene was applied as an internal standard. The samples were chromatographed on a LiChrosorb RP-18 (10 microns) column and the mobile phase was acetonitrile/phosphate buffer pH 2.70 (9:1). The detection was carried at 254 nm. A linear quantitative response curve was generated over a concentration range of 100-600 ng/ml. Overall extraction efficiency of the extraction procedure was found to be 86 to 91% with a correlation coefficient of 0.992.

  2. NUTRITIONAL THERAPY IN THE TREATMENT OF ACUTE CORROSIVE INTOXICATION IN ADULTS

    PubMed Central

    Chibishev, Andon; Markoski, Velo; Smokovski, Ivica; Shikole, Emilija; Stevcevska, Aleksandra

    2016-01-01

    Introduction: Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT. Aim: The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications. Discussion: Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications. Conclusion: It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment. PMID:27047272

  3. Peptide nanomedicines for treatment of acute lung injury.

    PubMed

    Sadikot, Ruxana T

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients. Despite the increased understanding of the molecular pathogenesis of ARDS, the mortality remains unacceptably high, ranging from 34% to 64%. Hence, ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Several promising targets that have been identified as potential therapies for ARDS have been limited because of difficulty with delivery. In particular, delivery of peptides and proteins to the lung is an ongoing challenge. Nanobiotechnology and nanoscience are the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmakodynamics of agents allowing an increase in the biodistribution of therapeutic agents to target organs, resulting in improved efficacy with reduction in drug toxicity. These systems are exploited for therapeutic purpose to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. Hence, it is an attractive strategy to test potential targets for ALI/ARDS using nanotechnology. To this end, we have identified several potential targets and proposed the delivery of these agents using nanomicelles to improve the drug delivery.

  4. [Diagnosis and treatment in the emergency room of acute asthma in childhood].

    PubMed

    Aldana Vergara, Ruth Saraí; Olivar Lòpez, Victor; Sienra Monge, Juan José Luis; Lezana Fernández, José Luis; Zepeda Ortega, Benjamin

    2009-01-01

    Acute asthma is characterized by acute air way obstruction episodes presented as short breath, increased coughing, wheezing and difficult breathing, reversible with bronchodilator. It constitutes one of the most frequent causes of pediatric ER visits whose diagnosis and treatment is not always adequate. It is necessary to carry out a complete medical history searching for the number of previous attacks, risk factors, associated illnesses, triggers, prior hospitalizations, preventive and maintenance treatment used, along with a complete physical examination. During the management of moderate-severe attacks frequent systematic assessments are required to ensure treatment response. In children above 5 years old, monitoring of expiratory peak flow (EPF) during mild-moderate attacks is recommended. In general, a national consensus to classify and treat acute asthma in emergency services does not exist for which the need to develop a clinical practice guide of diagnosis and management arises.

  5. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  6. Review article: lack of effect of opiates in the treatment of acute cardiogenic pulmonary oedema.

    PubMed

    Sosnowski, Marcin A

    2008-10-01

    Opiates have traditionally been used as one of the main treatments of acute heart failure and are still recognized as such. Most current textbooks and official guidelines advise the use of morphine as one of the first-line treatments for patients in acute cardiogenic pulmonary oedema and a majority of physicians accept it to be the case. The author performed an extensive literature search in order to validate the evidence for the use of opiates in this condition. A total of seven papers, six in English and one in Polish, were found that directly investigated or reported the clinically important outcomes of treatment of acute pulmonary oedema. Only five of these dealt specifically with the effects of administration of opiates in acute cardiogenic pulmonary oedema. None of the above publications suggested a clinically significant improvement in outcomes of patients treated with morphine, although early research did suggest reduced anxiety, blood pressure and pulse rate as well as a reduction in arterial oxygen contents. The more recent studies suggest a strong association between increased mortality and morbidity (e.g. intensive care unit admissions or intubation rates), although causality is difficult to establish because of research methodologies. The current evidence does not support the routine use of opiates in the treatment of acute pulmonary oedema.

  7. Comparison of efficacy, safety and brain derived neurotrophic factor (BDNF) levels in patients of major depressive disorder, treated with fluoxetine and desvenlafaxine.

    PubMed

    Ghosh, R; Gupta, R; Bhatia, M S; Tripathi, A K; Gupta, L K

    2015-12-01

    This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with fluoxetine and desvenlafaxine. Patients (aged 18-60 years) with moderate to severe major depressive disorder (MDD) diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥14, who were prescribed fluoxetine or desvenlafaxine were included (n=30 in each group). Patients were followed up for 12 weeks for evaluation of clinical efficacy, safety along with BDNF levels. In the fluoxetine group, HAM-D scores at the start of treatment was 19±4.09 which significantly (p<0.05) reduced to 9.24±3.98 at 12 weeks. In the desvenlafaxine group, HAM-D scores at the start of treatment was 18±3.75 which significantly (p<0.05) reduced to 10±3.75 at 12 weeks. The BDNF levels in the fluoxetine group were 775.32±30.38pg/ml at the start of treatment which significantly (p<0.05) increased to 850.3±24.92pg/ml at 12 weeks. The BDNF levels in the desvenlafaxine group were 760.5±28.53pg/ml at the start of treatment which significantly (p<0.05) increased to 845.8±32.82pg/ml at 12 weeks. Both the antidepressants were found to be safe and well tolerated. The efficacy and the safety profile of desvenlafaxine is comparable to fluoxetine in patients of MDD. BDNF levels were significantly increased post-treatment with both the antidepressive agents. Whether BDNF may have a prognostic value in predicting treatment response to antidepressant drugs needs to be investigated in a larger patient population.

  8. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder.

    PubMed

    Jazayeri, Shima; Keshavarz, Seyed A; Tehrani-Doost, Mehdi; Djalali, Mahmood; Hosseini, Mostafa; Amini, Homayoun; Chamari, Maryam; Djazayery, Abolghassem

    2010-06-30

    Treatment studies have suggested that omega-3 fatty acids (omega-3 FAs) as monotherapy or adjunctive treatment have therapeutic effects in depression. The authors recently reported a study in which fluoxetine and eicosapentaenoic acid (EPA), which is an omega-3 fatty acid, appeared to be equally effective in controlling depressive symptoms and their combination was superior to either of them alone. Regulation of hypothalamus-pituitary-adrenal (HPA) axis activity and reduction of inflammatory cytokines are among several biological mechanisms which potentially explain the impact of omega-3 FAs on depression. In the present study, plasma cortisol and serum interleukin-1beta (IL-1 beta) and interleukin-6 (Il-6) were measured in patients with a diagnosis of major depressive disorder (MDD) participating in aforementioned trial to determine the effects of 8 weeks of treatment of depression with 1000 mg EPA alone or in combination with 20 mg fluoxetine on HPA axis activity and inflammatory cytokine production and compare the changes in these variables with those of treating with 20 mg fluoxetine alone. Forty-two patients were included in analysis. Two-way repeated measures analysis of variance (ANOVA) showed that plasma cortisol decreased significantly after 8 weeks of intervention without significant difference among the groups. There was no interaction between group and response to treatment over time in the cortisol response based on three-way ANOVA. Serum concentrations of IL-1beta and IL-6 did not change significantly after intervention. In conclusion, EPA alone or in combination with fluoxetine, as well as fluoxetine alone decreased serum cortisol after 8 weeks of treatment in patients with major depression disorder (MDD) without any significant effect of response to treatment. Serum IL-1beta and IL-6 did not change significantly after intervention. These findings suggest that EPA may exert its therapeutic effects through reduction of cortisol.

  9. Treatment of compartment syndrome of the thigh associated with acute renal failure after the Wenchuan earthquake.

    PubMed

    Duan, Xin; Zhang, Kaiwei; Zhong, Gang; Cen, Shiqiang; Huang, Fuguo; Lv, Jingtong; Xiang, Zhou

    2012-04-01

    Compartment syndrome of the thigh is a rare emergency often treated operatively. The purpose of this study was to evaluate the effects of nonoperative treatment for compartment syndrome of the thigh associated with acute renal failure after the 2008 Wenchuan earthquake. Nonoperative treatment, which primarily involves continuous renal replacement therapy, was performed in 6 patients (3 men and 3 women) who presented with compartment syndrome of the thigh associated with acute renal failure. The mean mangled extremity severity score (MESS) and laboratory data regarding renal function were analyzed before and after treatment, and the clinical outcome was evaluated at 17-month follow-up. Laboratory data regarding renal function showed improvements. All 6 patients survived with the affected lower limbs intact after nonoperative treatment. Follow-up revealed active knee range of motion and increased muscle strength, as well as a recovery of sensation. A positive linear correlation was found between MESS and the time required to achieve a reduction in swelling, as well as the time required for the recovery of sensation and knee range of motion (r>0.8; P<.05). Satisfactory clinical outcomes were obtained in patients with compartment syndrome of the thigh associated with acute renal failure.Urine alkalization, electrolyte and water balance, and continuous renal replacement therapy have played an important role in saving lives and extremities. Nonoperative treatment should be considered in the treatment of compartment syndrome of the thigh associated with acute renal failure.

  10. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment.

  11. Potential contribution of inorganic ions to whole effluent acute toxicity and genotoxicity during sewage tertiary treatment.

    PubMed

    Sun, Jian; Quan, Ying; Wang, Wei; Zheng, Shaokui; Liu, Xinchun

    2015-09-15

    Two acute toxicity tests (luminescent bacteria assay and cladoceran assay) and one genotoxicity test (broad bean assay) were used to evaluate whole effluent toxicity during the standard anion exchange resin-based pilot-scale sewage tertiary treatment that stably achieved significant dissolved organic carbon and inorganic ions reduction. The effect of six representative inorganic ions (i.e., Cl(-), SO4(2-), NO3(-)-N, NO2(-)-N, NH4(+)-N and PO4(3-)-P) on the acute toxicity and genotoxicity was further investigated. Significant whole effluent genotoxicity reduction was observed as an ∼ 57% micronucleated cell frequency reduction and ∼ 46% mitotic index increment during the pilot-scale periods, which should be attributed to significant organic removal since no significant (p ≥ 0.116) increase in genotoxicity was observed with the increase in these ionic concentrations. However, no significant (p ≥ 0.14) reductions were observed for whole effluent acute toxicity using two acute toxicity assays during the pilot-scale periods, and these inorganic ions, especially NH4(+)-N, contributed considerably to the acute toxicity. Based on Pearson correlation coefficients, whole effluent acute toxicity showed significant positive (p < 0.001, r ≥ 0.758) correlations with the NH4(+)-N concentration. Two optimal models were finally developed using step-wise multiple linear regression to predict the whole effluent acute toxicity via NH4(+)-N concentrations.

  12. Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

    PubMed Central

    Sabetnejad, Zahra; Assarian, Fatemeh; Omidi, Abdollah; Najarzadegan, Mohammad Reza

    2016-01-01

    Background Obsessive compulsive disorder (OCD) is a mental health concern due to its various negative consequences, especially in sexual function. Therefore, the treatment of sexual dysfunction in women with OCD is important in order to improve the patient’s marital function and mental health. Objectives To compare the sexual behavior and sexual and marital satisfaction in women with obsessive-compulsive disorder (OCD) before and after treatment with fluoxetine and cognitive behavior therapy Methods This randomized clinical trial was conducted at psychiatric and psychological counseling centers in Kashan (Iran) from January 2, 2014, to December 29, 2014. Fifty-eight women with OCD were included in the study. In order to compare the effectiveness of pharmacological treatment (fluoxetine) and psychological treatment, cognitive behavior therapy (CBT), 58 female patients with OCD (diagnosed based on DSM-IV-T criteria) were randomized equally to either fluoxetine (at a dose of 60–80 mg daily for 3 months) or CBT (10 45-minute sessions). OCD and sexual behavior status of the patients before and after the intervention was assessed with the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and Female Sexual Function Index (FSFI) questionnaire, respectively. The data were analyzed using SPSS version 22. To compare changes between the two groups, an independent T-test was used. Finally, the effects of all potential factors on treatment outcome were analyzed using factorial ANCOVA. Results The mean score for OCD in the fluoxetine group was 25.6 ± 4.8 at the beginning of the experiment and 18.79 ± 4.26 at the end of the study, while in the CBT group it was 25.6 ± 4.8 and 18.79 ± 4.26, respectively. No significant differences were found between two groups regarding obsession score changes. These scores in fluoxetine group were 58.1 and 52.8, respectively (p=0.046). There was a significant difference between the two groups in terms of sexual performance (p=0

  13. [Treatment of acute pyoinflammatory diseases of the lungs and pleura under control of microorganism persistence factors].

    PubMed

    Abramzon, O M; Bukharin, O V; Kurlaev, P P

    2004-01-01

    Results of treatment of patients with acute pulmonary abscess, acute empyema of the pleura and pyopneumothorax were analyzed. The local treatment of the main group of patients consisting of 50 persons included oxitocin in combination with antiseptics and antibiotics which facilitated maximal reduction of the persistent potential of the pathogenic agent, its rapid elimination from the purulent focus and allowed to get better results using conservative therapy. The obtained clinical effect confirmed the experimental data on pronounced inhibition of persistent properties of the bacterial pathogens with the complexes "antibiotic-oxitocin".

  14. Use of chlorhexidine gluconate and povidone iodine mouthwashes in the treatment of acute ulcerative gingivitis.

    PubMed

    Addy, M; Llewelyn, J

    1978-11-01

    A trial was conducted to compare the effectiveness of povidone iodine and chlorhexidine gluconate with buffered peroxyborate in the treatment of acute ulcerative gingivitis. After 20 patients had entered the trial and 11 had required additional therapy with metronidazole to control their symptoms, the study was terminated. Those patients receiving peroxyborate all showed a satisfactory improvement in clinical signs and symptoms. One patient each receiving povidone iodine or chlorhexidine reported a symptomatic improvement, although gingival ulceration was still apparent at 1 week. The remaining patients all required metronidazole therapy to control their symptoms. Povidone iodine and chlorhexidine gluconate therefore cannot be recommended for the treatment of acute ulcerative gingivitis.

  15. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  16. Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

    ERIC Educational Resources Information Center

    Bola, John R.

    2006-01-01

    Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

  17. Management of acute renal failure in the elderly. Treatment options.

    PubMed

    Mandal, A K; Baig, M; Koutoubi, Z

    1996-10-01

    Renal changes that occur with aging mainly consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risk of volume depletion and the prerenal type of acute renal failure (ARF) in elderly people. Bladder outlet obstruction caused by benign prostatic hypertrophy is a common cause of ARF in elderly men. Another frequent cause of ARF in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics are most often implicated in the development of ARF in the elderly. However, considering the high usage of these drugs, the incidence of drug-induced nephropathy is relatively small. NSAIDs are more likely to cause ARF in patients with congestive heart failure, chronic renal disease (including diabetic nephropathy) or chronic liver disease than in otherwise healthy individuals. NSAID-induced ARF is often of the prerenal type, but may be caused by acute interstitial nephritis (AIN). The presence of heavy proteinuria or nephrotic syndrome differentiates NSAID-induced AIN from AIN caused by other drugs. Antibiotics, especially semisynthetic penicillins, more commonly give rise to AIN associated with peripheral blood eosinophilia and eosinophiluria than NSAIDs. Ciprofloxacin is increasingly reported to cause AIN. Fever commonly accompanies AIN, especially when induced by antibiotics. Aminoglycosides produce ARF by inducing acute tubular necrosis (ATN), which results from the excessive accumulation of myeloid bodies in the tubules. In all cases of ARF it is essential to obtain a good history, to perform a through physical examination, with particular attention to skin turgor, and to measure blood pressure, pulse rate (supine and upright), urinary electrolyte and creatinine levels. Fractional excretion of sodium and the urine:plasma creatinine ratio are reliable indices that distinguish prerenal ARF from ATN. A prompt response to fluid challenge, with an increase in

  18. Impramine, fluoxetine and clozapine differently affected reactivity to positive and negative stimuli in a model of motivational anhedonia in rats.

    PubMed

    Scheggi, S; Pelliccia, T; Ferrari, A; De Montis, M G; Gambarana, C

    2015-04-16

    Anhedonia is a relevant symptom in depression and schizophrenia. Chronic stress exposure induces in rats escape deficit, disrupts the dopaminergic response to palatable food and the competence to acquire sucrose self-administration (SA), thus configuring a possible model of motivational anhedonia. Repeated lithium administration reverts stress effects and brings back to control values the breaking point (BP) score, a measure of reward motivation. In this study, we tested on this model two antidepressants, imipramine and fluoxetine, and two antipsychotics, haloperidol and clozapine. The dopaminergic response to sucrose consumption was studied in non food-deprived rats in terms of dopamine D1 receptor signaling in the nucleus accumbens shell (NAcS). More specifically, we studied the modifications in dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32) phosphorylation pattern following sucrose consumption. Fluoxetine reverted the escape deficit and showed no effects on dopaminergic response and sucrose SA. Imipramine reverted sucrose SA and dopamine response deficit in half of the rats and the escape deficit in all animals. Haloperidol did not affect stress-induced deficits. Clozapine-treated rats recovered the dopaminergic response to sucrose consumption and the competence to acquire sucrose SA, although they still showed the escape deficit, thus confirming that motivation toward reward may be dissociated from that to punishment escape. These results indicate that imipramine or fluoxetine are not endowed with a rapid onset antianhedonic effect. On the other hand, clozapine treatment showed a motivational antianhedonic activity similar to that observed after lithium treatment.

  19. Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis

    PubMed Central

    Gultekin, Fatma Ayca; Kerem, Mustafa; Tatlicioglu, Ertan; Aricioglu, Aysel; Unsal, Cigdem; Bukan, Neslihan

    2007-01-01

    AIM: To determine the effect of exogenous leptin on acute lung injury (ALI) in cerulein-induced acute pancreatitis (AP). METHODS: Forty-eight rats were randomly divided into 3 groups. AP was induced by intraperitoneal (i.p.) injection of cerulein (50 μg/kg) four times, at 1 h intervals. The rats received a single i.p. injection of 10 μg/kg leptin (leptin group) or 2 mL saline (AP group) after cerulein injections. In the sham group, animals were given a single i.p. injection of 2 mL saline. Experimental samples were collected for biochemical and histological evaluations at 24 h and 48 h after the induction of AP or saline administration. Blood samples were obtained for the determination of amylase, lipase, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, macrophage inflammatory peptide (MIP)-2 and soluble intercellular adhesion molecule (sICAM)-1 levels, while pancreatic and lung tissues were removed for myeloperoxidase (MPO) activity, nitric oxide (NOx) level, CD40 expression and histological evaluation. RESULTS: Cerulein injection caused severe AP, confirmed by an increase in serum amylase and lipase levels, histopathological findings of severe AP, and pancreatic MPO activity, compared to the values obtained in the sham group. In the leptin group, serum levels of MIP-2, sICMA-1, TNF-α, and IL-1β, pancreatic MPO activity, CD40 expression in pancreas and lung tissues, and NOx level in the lung tissue were lower compared to those in the AP group. Histologically, pancreatic and lung damage was less severe following leptin administration. CONCLUSION: Exogenous leptin attenuates inflamma-tory changes, and reduces pro-inflammatory cytokines, nitric oxide levels, and CD40 expression in cerulein-induced AP and may be protective in AP associated ALI. PMID:17589942

  20. Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.

    PubMed

    Gassó, Patricia; Rodríguez, Natalia; Blázquez, Ana; Monteagudo, Ana; Boloc, Daniel; Plana, Maria Teresa; Lafuente, Amalia; Lázaro, Luisa; Arnaiz, Joan Albert; Mas, Sergi

    2017-04-03

    The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants.

  1. [Emergency antibiotherapy and adjuvant treatments for acute bacterial meningitis].

    PubMed

    Mourvillier, B

    2009-01-01

    The management of bacterial meningitis is based on the combination of several components. The objective of this review is to give an overview of the literature concerning both the arguments for urgent antibiotic treatment associated with a particular focus on the place of corticosteroids. Among other treatments, glycerol seems the best rated but symptomatic measures, which may not be achieved by randomized studies, should not be overlooked. Many animal studies explore other treatment options, but none can be translated into clinical practice. The neuroimaging has been little evaluated despite recent technological advances but remains important in monitoring of patients whose evolution is considered unfavorable.

  2. Study strategies for bloodletting therapy in treatment of acute soft tissue injuries.

    PubMed

    Chen, Peng-Dian; Chen, Gui-Zhen; Xu, Yun-Xiang

    2011-03-01

    Bloodletting therapy is one of the typical treatment modes of traditional Chinese medicine, and acute soft tissue injury (ASTI) is one of the most common indications for acupuncture therapeutics. In this paper, the current situation of treatments and pathological mechanisms of ASTIs, the existing problems of bloodletting therapy in the treatment of ASTIs and the study strategies are systematically analyzed, indicating that bloodletting therapy is significantly effective in the treatment of ASTIs. Breakthroughs in the treatment of ASTIs will be achieved with the application of bloodletting therapy both in clinical practice and experimental research.

  3. Magnetic resonance diffusion tensor imaging following major ozonated autohemotherapy for treatment of acute cerebral infarction

    PubMed Central

    Wu, Xiao-na; Zhang, Tao; Wang, Jun; Liu, Xiao-yan; Li, Zhen-sheng; Xiang, Wei; Du, Wei-qing; Yang, Hong-jun; Xiong, Tie-gen; Deng, Wen-ting; Peng, Kai-run; Pan, Su-yue

    2016-01-01

    Major ozonated autohemotherapy has been shown to promote recovery of upper limb motor function in patients with acute cerebral infarction, but whether major ozonated autohemotherapy affects remote injury remains poorly understood. Here, we assumed that major ozonated autohemotherapy contributes to recovery of clinical function, possibly by reducing remote injury after acute cerebral infarction. Sixty acute cerebral infarction patients aged 30–80 years were equally and randomly allocated to ozone treatment and control groups. Patients in the ozone treatment group received medical treatment and major ozonated autohemotherapy (47 mg/L, 100 mL ozone) for 10 ± 2 days. Patients in the control group received medical treatment only. National Institutes of Health Stroke Scale score, modified Rankin scale score, and reduced degree of fractional anisotropy values of brain magnetic resonance diffusion tensor imaging were remarkably decreased, brain function improved, clinical efficiency significantly increased, and no obvious adverse reactions detected in the ozone treatment group compared with the control group. These findings suggest that major ozonated autohemotherapy promotes recovery of neurological function in acute cerebral infarction patients by reducing remote injury, and additionally, exhibits high safety. PMID:27630695

  4. Hyponatremia associated with sertraline and fluoxetine: a case report.

    PubMed

    Raphael, Kalani; Tokeshi, Jinichi

    2002-03-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a rare but serious adverse effect of the selective serotonin reuptake inhibitors (SSRIs). Although many case reports describe this association, few report the effect of rechallenge with another SSRI. We present a case of an elderly patient who developed hyponatremia with sertraline and SIADH when rechallenged with fluoxetine.

  5. Fluoxetine potentiates nitrazepam-induced behavioral sleep in young chicks.

    PubMed

    Hussaini, I M; Musa, M H

    1994-02-01

    Nitrazepam (0.5-10 mg/kg, IP) dose dependently induced behavioral sleep in day-old chicks. Fluoxetine (0.1-1 mg/kg) did not produce sleep in the young birds, but the 5-HT reuptake inhibitor (0.1 and 0.5 mg/kg) potentiated nitrazepam (0.5 and 1.0 mg/kg)-induced hypnosis. Doses (0.5 and 1 mg/kg) of the benzodiazepine that did not produce sleep in any or all the chicks, when administered alone, induced sleep in some or all the chicks in the presence of fluoxetine (0.1 and 0.5 mg/kg). Ketanserin (0.5 and 2.5 mg/kg) effectively antagonized the effect of fluoxetine on nitrazepam-induced behavioral sleep. These results suggest that enhancement of 5-HT level by fluoxetine may be the mechanism involved in the potentiation of nitrazepam-induced sleep in the young chicks.

  6. Current concepts for the treatment of acute scaphoid fractures.

    PubMed

    Arsalan-Werner, A; Sauerbier, M; Mehling, I M

    2016-02-01

    Fractures of the scaphoid are common injuries, accounting for approximately 80 % of carpal fractures. Differentiation between stable and unstable fractures (Herbert classification) cannot be made with conventional X-rays, so evaluation by computed tomography should additionally be performed. Under most circumstances, minimally invasive surgery with cannulated screws is the treatment of choice. A longer cast immobilization after minimal-invasive surgery is not necessary. Conservative treatment still has a place if the fracture is not dislocated nor unstable, but operative treatment can be offered to reduce the period of cast immobilization. Displaced fractures have a greater risk for nonunion and therefore should be treated operatively. Proximal pole fractures are definitely unstable, requiring treatment with screw fixation. The surgical approach depends on the location of the fracture and the preference of the surgeon.

  7. [The particularities of acute surgical diseases treatment of abdominal cavity organs in patients with haemophilia].

    PubMed

    Shutov, S A; Karagiulia, S R; Danishian, K I; Zorenko, V Iu; Grzhimolovskiĭ, A V; Polianskaia, T Iu; Shulutko, E M; Galstian, G M

    2014-01-01

    The experience of treatment of 366 patients with haemophilia who were urgently hospitalized in hеmatological Scientific Center over the last 10 years is presented in the article. There were 114 (31.1%) patients with acute diseases of abdominal cavity organs, 150 (41%) patients with bleeding from upper gastrointestinal tract, 102 (27.9%) patients with acute hematomas of retroperitoneal space. Urgent operations were performed in 48 (22.2%) patients who were hospitalized with clinical symptoms of acute abdomen syndrome. It was developed the criteria of diagnosis and choice of treatment tactic on the basis of the received results. Application of presented algorithms led to improve the quality of urgent surgical care to patients with haemophilia.

  8. [Peculiarities of treatment of the aged and elderly patients with acute pancreatitis].

    PubMed

    Shevchuk, I M; Kuzenko, R T

    2013-11-01

    The results of treatment of 99 elderly and senile patients, suffering an acute pancreatitis in period of 2005 - 2013 yrs, were analyzed. Interstitial acute pancreatitis was diagnoses in 36 (36.3%) patients, focal pancreatic necrosis--in 32 (32.3%), total-subtotal pancreonecrosis--in 31 (31.3%). Miniinvasive interventions were performed in 40 (63.4%) patients, the open--in 24 (38%). The main indication for laparotomy conduction were purulent-septic complications, which is impossible to eliminate while miniinvasive methods application. Due to application of the staged treatment tactics with predominant application of miniinvasive methods, extracorporeal detoxication and improvement of the intensive therapy measures postoperative lethality in necrotic acute pancreatitis have had lowered from 16.7 to 10.3%.

  9. Treatment of severe acute pancreatitis and its complications.

    PubMed

    Zerem, Enver

    2014-10-14

    Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder.

  10. Treatment of severe acute pancreatitis and its complications

    PubMed Central

    Zerem, Enver

    2014-01-01

    Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

  11. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens

    PubMed Central

    Pratz, Keith; Levis, Mark

    2011-01-01

    FMS-Like-Tyrosine kinase-3 (FLT3) mutations are found in about 30% of cases of acute myeloid leukemia and confer an increased relapse rate and reduced overall survival. Targeting of this tyrosine kinase by direction inhibition is the focus of both preclinical and clinical research in AML. Several molecules in clinical development inhibit FLT3 with varying degrees of specificity. Preclinical models suggest that these compounds enhance the cytotoxicity of conventional chemotherapeutics against FLT3 mutant leukemia cells. The pharmacodynamic interactions between FLT3 inhibitors and chemotherapy appear to be sequence dependent. When the FLT3 inhibitor is used prior to chemotherapy, antagonism is displayed, while if FLT3 inhibition is instituted after to exposure to chemotherapy, synergistic cytotoxicity is seen. The combination of FLT3 inhibitors with chemotherapy is also complicated by potential pharmacokinetic obstacles, such as plasma protein binding and p-glycoprotein interactions. Ongoing and future studies are aimed at incorporating FLT3 inhibitors into conventional induction and consolidation therapy specifically for patients with FLT3 mutant AML. PMID:18452067

  12. Treatment of acute kidney injury with cast nephropathy.

    PubMed

    Walther, Carl; Podoll, Amber S; Finkel, Kevin W

    2014-07-01

    Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type. Development of AKI is associated with worse 1-year survival and reduces the therapeutic options available to patients. Therefore, there is a great need to develop more effective therapies. Cast nephropathy is due to the interaction and aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP) causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of FLCs as this correlates with renal recovery. Newer chemotherapy agents lower FLCs and have been referred to as "renoprotective". However there remains great interest in using various extracorporeal therapies to remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to improve renal outcomes in cast nephropathy based on small trials. The largest randomized trial of TPE, however, failed to show any benefit. A newer technique is extended high cut-off hemodialysis (HCO-HD). This modality uses a high molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in patients with cast nephropathy have been encouraging. However, there are no randomized trials demonstrating the benefit of HCOHD when used in addition to newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot be recommended as standard of care.

  13. Current standard treatment of adult acute promyelocytic leukaemia.

    PubMed

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease.

  14. L-carnitine for the treatment of acute myocardial infarction.

    PubMed

    Dinicolantonio, James J; Niazi, Asfandyar K; McCarty, Mark F; Lavie, Carl J; Liberopoulos, Evangelos; O'Keefe, James H

    2014-01-01

    Although the therapeutic strategies available for treating acute myocardial infarction (AMI) have evolved dramatically in recent decades, coronary artery disease remains the leading cause of death in our society, and the rates of recurrent myocardial infarction and mortality are still unacceptably high. Therefore, exploration of alternative therapeutic strategies for AMI is of utmost importance. One such strategy is to target metabolic pathways via L-carnitine supplementation. L-carnitine is a physiologically essential metabolic cofactor that has been shown to provide a plethora of benefits when administered after AMI. L-carnitine has been shown to lessen infarct size, to reduce ventricular arrhythmias, left ventricular dilation, and heart failure incidence, as well as improve survival. These benefits may, in part, be related to its ability to boost glucose oxidation in ischemic tissues, while moderating increases in fatty acyl-coenzyme A levels that can impair mitochondrial efficiency and promote oxidative stress and inflammation. This article summarizes the evidence pertinent to the therapeutic use of L-carnitine for AMI.

  15. Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats.

    PubMed

    Gomes, Karin M; Inácio, Cecília G; Valvassori, Samira S; Réus, Gislaine Z; Boeck, Carina R; Dal-Pizzol, Felipe; Quevedo, João

    2009-11-06

    The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.

  16. Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment.

    PubMed

    Reznikov, Leah R; Grillo, Claudia A; Piroli, Gerardo G; Pasumarthi, Ravi K; Reagan, Lawrence P; Fadel, Jim

    2007-05-01

    Depressive illness is associated with changes in amygdalar volume, and stressful life events are known to precipitate depressive episodes in this patient population. Stress affects amygdalar synaptic plasticity and several neurotransmitter systems have been implicated in stress-mediated changes in the brain, including the glutamatergic system. However, the role of the glutamatergic system in stress-mediated plasticity in the amygdala remains to be determined. Accordingly the current study examined the stress modulation of extracellular glutamate levels in the basolateral nucleus (BLA) and the central nucleus (CeA) of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the BLA and CeA, although the dynamics of these stress-mediated changes were dramatically different in these amygdalar nuclei. Tetrodotoxin administration reduced basal, and completely eliminated stress-mediated increases in glutamate efflux in the amygdala, demonstrating that stress effects are dependent on local axonal depolarization. Moreover, stress-mediated increases in glutamate efflux in the BLA were inhibited by the antidepressant tianeptine but not by the selective serotonin-reuptake inhibitor fluoxetine. Collectively, these data demonstrate that stress-induced modulation of glutamate neurochemistry reflects a fundamental pathological change that may contribute to the aetiology and progression of depressive illness, and suggest that some antidepressants such as tianeptine may elicit their clinical effects by modulation of glutamatergic neurotransmission.

  17. Assessment, management and treatment of acute fingertip injuries.

    PubMed

    Kearney, Anthony; Canty, Louise

    2016-06-01

    Fingertip injuries with nail bed trauma can require specialist hand surgery, depending on severity. However, most of these injuries can be managed in well-equipped emergency departments by emergency nurses with an in-depth knowledge and understanding of the anatomy and physiology of the fingernail and surrounding structures, assessment and examination, pain management and treatment. This article describes the surface and underlying anatomy and physiology of the nail, the most common mechanisms of injury, relevant diagnostic investigations, and initial assessment and management. It also discusses treatment options, referral pathways, and patient discharge advice.

  18. [Intrapleural sorption detoxication in the combined treatment of acute destructive pneumonia in children].

    PubMed

    Kravchuk, B A; Sokur, P P; Makarov, A V; Spivak, N Ia; Nogareva, E M; Ganova, L A

    1993-01-01

    The pathogenetic substantiation and technique of intrapleural sorption detoxication (IPSD) based on the use of high-dispersed silicone dioxide (trade mark "AEROSIL") are presented. Use of IPSD in the complex of treatment of 25 children with complicated forms of acute destructive pneumonia permitted to shorten the duration of intoxication syndrome, sanation of suppurative foci, stay of the patients at a hospital.

  19. Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study

    SciTech Connect

    Pilepich, M.V.; Anderson, C.B.; Etheredge, E.E.; Sicard, G.A.; Melzer, J.S.; Blum, J.

    1982-05-01

    A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eighty-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steriods.

  20. Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight loss treatment.

    PubMed

    Pikkel, Yoav Yechezkel

    2014-04-17

    A 54-year-old male patient presented to our clinic with acute angle-closure glaucoma and panuveitis in both eyes after being treated with topiramate for binge eating and obesity. This case report emphasises the hazardous side effects of treatment with topiramate with unusual indication and the precaution a caretaker must take when treating a patient.

  1. Novel targeted drug therapies for the treatment of childhood acute leukemia

    PubMed Central

    Brown, Patrick; Hunger, Stephen P; Smith, Franklin O; Carroll, William L; Reaman, Gregory H

    2009-01-01

    The cure rates for childhood acute leukemia have dramatically improved to approximately 70% overal, with treatments that include intensive cytotoxic chemotherapy and, in some cases, hematopoietic stem cell transplantation. However, many children still die of their disease or of treatment-related toxicities. Even in patients that are cured, there can be significant and, not uncommonly debilitating, acute and late complications of treatment. Improved understanding of the molecular and cellular biology of leukemia and the increasing availability of high-throughput genomic techniques have facilitated the development of molecularly targeted therapies that have the potential to be more effective and less toxic than the standard approaches. In this article, we review the progress to date with agents that are showing promise in the treatment of childhood acute leukemia, including monoclonal antibodies, inhibitors of kinases and other signaling molecules (e.g., BCR–ABL, FLT3, farnesyltransferase, mTOR and γ-secretase), agents that target epigenetic regulation of gene expression (DNA methyltransferase inhibitors and histone deacetylase inhibitors) and proteasome inhibitors. For the specific agents in each of these classes, we summarize the published preclinical data and the clinical trials that have been completed, are in progress or are being planned for children with acute leukemia. Finally, we discuss potential challenges to the success of molecularly targeted therapy, including proper target identification, adequate targeting of leukemia stem cells, developing synergistic and tolerable combinations of agents and designing adequately powered clinical trials to test efficacy in molecularly defined subsets of patients. PMID:20126514

  2. A case of enoxaparin-induced thrombocytopaenia during treatment of acute myocardial infarction.

    PubMed

    Lim, Snag Yup; Lee, Se Ryeon; Kim, Yong Hyun; Kim, Jin Seok; Kim, Seong Hwan; Ahn, Jeong Chun; Song, Woo Hyuk

    Heparin-induced thrombocytopaenia is a life-threatening complication, affecting the morbidity and mortality of the patient if not properly treated. We report a case of a 75-year-old female patient who experienced enoxaparininduced thrombocytopaenia during medical treatment of acute ST-segment elevation myocardial infarction due to thrombotic total occlusion in the large right coronary artery.

  3. [Acute appendicitis. Surgical and non-surgical treatment].

    PubMed

    Souza-Gallardo, Luis Manuel; Martínez-Ordaz, José Luis

    2017-01-01

    Appendicitis represents a common disease for the surgeon with a relative risk between 7-8%. It was thought that if more time passed between diagnosis and treatment, the risk for complications, such as perforation or abscess formation, was higher; nevertheless; the evolution is variable, making necessary the development of different strategies such as antibiotic use only, interval surgery or endoscopic treatment. The purpose of this study is to make a revision in the management of appendicitis comparing conservative and surgical treatment. It is known that traditional management of appendicitis is appendectomy with a complication rate of 2.5% to 48%. Nowadays, laparoscopy is the approach of choice by many surgeons and there have proposed new invasive techniques such as endoscopic treatment with the use of prosthesis and ambulatory surgery. Antibiotic use is essential in the management of appendicitis. Its use as the only strategy to treat this disease has the purpose of lowering costs and diminishing complications related to surgery or the resection of the organ. We conclude that the ideal management of appendicitis remains controversial and it will depend of the clinical characteristics of each patient and the resources available.

  4. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  5. Acute Thrombotic Mesenteric Ischemia: Primary Endovascular Treatment in Eight Patients

    SciTech Connect

    Gagniere, Johan; Favrolt, Gregory; Alfidja, Agaiecha; Kastler, Adrian; Chabrot, Pascal; Cassagnes, Lucie; Buc, Emmanuel; Pezet, Denis; Boyer, Louis

    2011-10-15

    Introduction: The purpose of this study was to evaluate our experience with initial percutaneous transluminal angioplasty (PTA) {+-} stenting as valuable options in the acute setting. Methods: Between 2003 and 2008, eight patients with abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA {+-} stenting. We retrospectively assessed clinical and radiological findings and their management. Seven patients presented thrombosis of the superior mesenteric artery, and in one patient both mesenteric arteries were occluded. All patients underwent initial PTA and stenting, except one who had balloon PTA alone. One patient was treated by additional in situ thrombolysis. Results: Technical success was obtained in all patients. Three patients required subsequent surgery (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score {>=}4, and severe radiologic findings. Satisfactory arterial patency was observed after a follow-up of 15 (range, 11-17) months in five patients who did not require subsequent surgery, four of whom had abdominal guarding but no severe CT scan findings. One patient had an ileocecal stenosis 60 days after the procedure. Conclusions: Initial PTA {+-} stenting is a valuable alternative to surgery for patients with thrombotic AMI even for those with clinical peritoneal irritation signs and/or severe radiologic findings. Early surgery is indicated if clinical condition does not improve after PTA. The decision of a subsequent surgery must be lead by early clinical status reevaluation. In case of underlying atherosclerotic lesion, stenting should be performed after initial balloon dilatation.

  6. Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine.

    PubMed

    Golub, Mari S; Bulleri, Alicia M; Hogrefe, Casey E; Sherwood, Richard J

    2015-10-01

    Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25-39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs.

  7. World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Yoon, Sang-In; Park, Dong-Hyuk; Kang, Shin-Hyuk; Park, Jung-Yul; Chung, Yong-Gu

    2016-01-01

    When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment. PMID:27867928

  8. The pros and cons of endovascular and open surgical treatments for patients with acute limb ischemia.

    PubMed

    Branco, B C; Montero-Baker, M F; Mills, J L

    2015-06-01

    The present review addresses the pros and cons of the current, wide variety of therapeutic options available for the treatment of acute limb ischemia (ALI). Despite five prospective randomized controlled trials comparing catheter directed thrombolysis and open surgical revascularization, no single treatment strategy can yet be considered optimal for patients with ALI. This report includes 20 years of published data to evaluate the efficacy and safety profile of thrombolytic agents and adjunctive endovascular techniques when compared to open surgical revascularization.

  9. Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis

    PubMed Central

    Brouwer, Matthijs C.; Tunkel, Allan R.; van de Beek, Diederik

    2010-01-01

    Summary: The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease. PMID:20610819

  10. [Extended hemoperfusion in the treatment of acute carbamazepine intoxication].

    PubMed

    Peces, R; Azorín, S; Peces, C; Selgas, R

    2010-01-01

    Carbamazepine is used in the treatment of epilepsy, and also prescribed in neuralgic pain syndromes, and certain affective disorders. Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, arrhythmia, hemodynamic instability and death. The drug's relatively high molecular weight, elevated volume of distribution and intense protein-binding render it difficult to extracorporeal removal, but published experience with hemoperfusion or hemodialysis present variable results. We describe a case report involving carbamazepine intoxication who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of carbamazepine was reduced with rapid lowering of carbamazepine levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, extended charcoal hemoperfusion should be considered for serious carbamazepine intoxication because free as well as bound drug fractions are eliminated via this technique.

  11. [Hemoperfusion in the treatment of acute valproic acid intoxication].

    PubMed

    Peces, R; Fernández, E J; Sánchez, R J; Peces, C; Montero, A; Selgas, R

    2007-01-01

    Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. Valproic acid intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, pancytopenia, hemodynamic instability and death. The drug's relatively low molecular weight, small volume of distribution and saturable protein-binding render it potentially amenable to exracorporeal removal (hemodialysis, hemoperfusion or hemofiltration ), but published experience is scarce. We describe a case report involving valproic acid intoxication with ingestion of ethanol, who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of valproic acid was reduced with rapid lowering of valproic acid levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, charcoal hemoperfusion should be considered for serious valproic acid intoxication because free as well as bound drug fractions are eliminated via this technique.

  12. Interventional treatment for symptomatic acute-subacute portal and superior mesenteric vein thrombosis

    PubMed Central

    Liu, Feng-Yong; Wang, Mao-Qiang; Fan, Qing-Sheng; Duan, Feng; Wang, Zhi-Jun; Song, Peng

    2009-01-01

    AIM: To summarize our methods and experience with interventional treatment for symptomatic acute-subacute portal vein and superior mesenteric vein thrombosis (PV-SMV) thrombosis. METHODS: Forty-six patients (30 males, 16 females, aged 17-68 years) with symptomatic acute-subacute portal and superior mesenteric vein thrombosis were accurately diagnosed with Doppler ultrasound scans, computed tomography and magnetic resonance imaging. They were treated with interventional therapy, including direct thrombolysis (26 cases through a transjugular intrahepatic portosystemic shunt; 6 through percutaneous transhepatic portal vein cannulation) and indirect thrombolysis (10 through the femoral artery to superior mesenteric artery catheterization; 4 through the radial artery to superior mesenteric artery catheterization). RESULTS: The blood reperfusion of PV-SMV was achieved completely or partially in 34 patients 3-13 d after thrombolysis. In 11 patients there was no PV-SMV blood reperfusion but the number of collateral vessels increased significantly. Symptoms in these 45 patients were improved dramatically without severe operational complications. In 1 patient, the thrombi did not respond to the interventional treatment and resulted in intestinal necrosis, which required surgical treatment. In 3 patients with interventional treatment, thrombi re-formed 1, 3 and 4 mo after treatment. In these 3 patients, indirect PV-SMV thrombolysis was performed again and was successful. CONCLUSION: Interventional treatment, including direct or indirect PV-SMV thrombolysis, is a safe and effective method for patients with symptomatic acute-subacute PV-SMV thrombosis. PMID:19859995

  13. Rapid Response to Treatment for Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  14. Medical treatment of acute poisoning with organophosphorus and carbamate pesticides.

    PubMed

    Jokanović, Milan

    2009-10-28

    Organophosphorus compounds (OPs) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OP can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the nervous systems. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OP. They act by reactivation of AChE inhibited by OP. However, they differ in their activity in poisoning with pesticides and warfare nerve agents and there is still no universal broad-spectrum oxime capable of protecting against all known OP. In spite of enormous efforts devoted to development of new pyridinium oximes as potential antidotes against poisoning with OP only four compounds so far have found its application in human medicine. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans. In this article the available data related to medical treatment of poisoning with OP pesticides are reviewed and the current recommendations are presented.

  15. Advances in medical revascularisation treatments in acute ischemic stroke.

    PubMed

    Asadi, H; Yan, B; Dowling, R; Wong, S; Mitchell, P

    2014-01-01

    Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials.

  16. Extreme Response Style in Recurrent and Chronically Depressed Patients: Change with Antidepressant Administration and Stability during Continuation Treatment

    ERIC Educational Resources Information Center

    Peterson, Timothy J.; Feldman, Greg; Harley, Rebecca; Fresco, David M.; Graves, Lesley; Holmes, Avram; Bogdan, Ryan; Papakostas, George I.; Bohn, Laurie; Lury, R. Alana; Fava, Maurizio; Segal, Zindel V.

    2007-01-01

    The authors examined extreme response style in recurrently and chronically depressed patients, assessing its role in therapeutic outcome. During the acute phase, outpatients with major depressive disorder (N = 384) were treated with fluoxetine for 8 weeks. Remitted patients (n = 132) entered a continuation phase during which their fluoxetine dose…

  17. Treatment of acute cerebral ischemia using animal models: a meta-analysis

    PubMed Central

    Wang, Peng-Fei; Zhou, Yu; Fang, Huang; Lin, Sen; Wang, Yan-Chun; Liu, Yong; Xia, Jun; Eslick, Guy D.; Yang, Qing-Wu

    2015-01-01

    Background There are numerous potential treatments assessed for acute cerebral ischemia using animal models. This study aimed to assess the effect of these treatments in terms of infarct size and neurobehavioral change. This meta-analysis was conducted to determine if any of these treatments provide a superior benefit so that they might be used on humans. Methods A systematic search was conducted using several electronic databases for controlled animal studies using only nonsurgical interventions for acute cerebral ischemia. A random-effects model was used. Results After an extensive literature search, 145 studies were included in the analysis. These studies included 1408 treated animals and 1362 control animals. Treatments that had the most significant effect on neurobehavioral scales included insulin, various antagonists, including N-methyl-D-aspartate (NMDA) receptor antagonist ACEA1021, calmodulin antagonist DY-9760e, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist YM872, and antiviral agents. Treatments providing the greatest effect on infarct size included statins, sphingosine-1-phosphate agonist (fingolimod), alcohol, angiotensin, and leukotrienes. Treatments offering the greatest reduction in brain water content included various agonists, including sphingosine-1-phosphate agonist fingolimod, statins, and peroxisome proliferator-activated receptor gamma (PPAR-γ). Treatment groups with more than one study all had high heterogeneity (I2 > 80%), however, using meta-regression we determined several sources of heterogeneity including sample size of the treatment and control groups, the occlusion time, but not the year when the study was conducted. Conclusions Some treatments stand out when compared to others for acute cerebral ischemia in animals. Greater replication of treatment studies is required before any treatments are selected for future human trials. PMID:28123790

  18. Group vs. Individual Treatment for Acute Insomnia: A Pilot Study Evaluating a “One-Shot” Treatment Strategy

    PubMed Central

    Boullin, Pam; Ellwood, Christina; Ellis, Jason G.

    2016-01-01

    Background: Despite undeniable evidence for the efficacy and effectiveness of Cognitive Behaviour Therapy for Insomnia (CBT-I), the potential for its widespread dissemination and implementation has yet to be realised. A suggested reason for this is that traditional CBT-I is considered too burdensome for deployment, in its current form, within the context of where it would be most beneficial—Primary Care. One strategy, aimed to address this, has been to develop briefer versions of CBT-I, whilst another has been to deliver CBT-I in a group format. An alternative has been to attempt to address insomnia during its acute phase with a view to circumventing its progression to chronic insomnia. The aim of the present study was to compare a brief version of CBT-I (one-shot) when delivered individually or in groups to those with acute insomnia. Method: Twenty-eight individuals with acute insomnia (i.e., meeting full DSM-5 criteria for insomnia disorder for less than three months) self-assigned to either a group or individual treatment arm. Treatment consisted of a single one-hour session accompanied by a self-help pamphlet. Subjects completed measures of insomnia severity, anxiety and depression pre-treatment and at one-month post-treatment. Additionally, daily sleep diaries were compared between pre-treatment and at the one-month follow up. Results: There were no significant between group differences in treatment outcome on any sleep or mood measures although those in the group treatment arm were less adherent than those who received individual treatment. Furthermore, the combined (group and individual treatment arms) pre-post test effect size on insomnia symptoms, using the Insomnia Severity Index, was large (d = 2.27). Discussion: It appears that group treatment is as efficacious as individual treatment within the context of a “one shot” intervention for individuals with acute insomnia. The results are discussed with a view to integrating one-shot CBT-I in Primary

  19. Treatment Strategies for Acute Ischemic Stroke Caused by Carotid Artery Occlusion

    PubMed Central

    Li, Wei; Yin, Qin; Xu, Gelin; Liu, Xinfeng

    2016-01-01

    Background: Acute ischemic stroke caused by internal carotid artery (ICA) occlusion usually has a poor prognosis, especially the T occlusion cases without functional collaterals. The efficacy of intravenous (IV) or intra-arterial (IA) thrombolysis with recombinant tissue plasminogen activator (rt-PA) remains ambiguous in these patients. Eendovascular recanalization of the occluded carotid has been attempted in recent years as a potential strategy. However, the different etiologies of ICA occlusion pose a significant challenge to neurointerventionists. Recently, several endovascular evolvements have been reported in treating carotid occlusion-related stroke. This review summarizes the current status of treatment for acute ICA occlusion. PMID:27781043

  20. [Use of xenogenic lyophilized hepatocytes in the treatment of acute and chronic liver diseases].

    PubMed

    Musselius, S G; Vasina, N V; Gladskikh, L V

    1998-01-01

    Therapeutic effect of lyophilized xenogenic hepatocytes was demonstrated on 30 dogs with acute hepatic failure and on white mice. The major biochemical values were corrected and the yeast fermentation test showed biological activity of isolated hepatocytes. Clinically, lyophilized hepatocytes were used in the treatment of patients with acute hepatic failure: orally in 47 and for extracorporeal dialysis in 8. The therapeutic effect of lyophilized hepatocytes is based on active detoxication and hemostasis correction. Clinical, laboratory, and instrumental studies showed improvement of the clinical status, decreased encephalopathy, and accelerated repair processes in the liver. Addition of lyophilized hepatocytes to combined therapy decreased the mortality by 2.5 times.

  1. Acupuncture Treatment for Acute Ankle Injury in the Emergency Department: A Preliminary Case Report.

    PubMed

    Tantivesruangdet, Nopmanee

    2016-02-01

    Acupuncture is an ancient medical treatment that is increasingly attracting the interest of the public. It is a complementary therapy that is widely used for management of pain, especially chronic discomfort caused by migraine, low-back pain and osteoarthritis of the knee(¹⁻³). The evidence base for the effectiveness of acupuncture and its clinical applications is controversial, and although its efficacy and safety in the management of acute pain have been demonstrated, the quality of this modality is still questionable. The present study reports a case of acute ankle injury, which was treated with acupuncture. A 33-year-old man presented with acute twisted ankle injury. He had pain with swelling around the ankle, and he was experiencing difficulty in walking. His clinical diagnosis was acute ankle sprain with severe pain. Several drug treatments are used for pain control, but in this case, we used acupuncture. After treatment, his pain diminished significantly with a decrease in VAS pain level from 8 to 4 in 20 minutes. At follow-up after one month, we found no skin infection in this case.

  2. Treatment Result in the Initial Stage of Kanazawa Mobile Embolectomy Team for Acute Ischemic Stroke

    PubMed Central

    UCHIYAMA, Naoyuki; MISAKI, Kouichi; MOHRI, Masanao; KAMIDE, Tomoya; HIROTA, Yuichi; HIGASHI, Ryo; MINAMIDE, Hisato; KOHDA, Yukihiko; ASAHI, Takashi; SHOIN, Katsuo; IWATO, Masayuki; KITA, Daisuke; HAMADA, Yoshitaka; YOSHIDA, Yuya; NAKADA, Mitsutoshi

    2016-01-01

    Five recent multicenter randomized controlled trials (RCTs) have clearly shown the superiority of mechanical thrombectomy in large vessel occlusion acute ischemic stroke compared to systemic thrombolysis. Although 14 hospitals in Ishikawa prefecture have uninterrupted availability of systemic thrombolysis, mechanical thrombectomy is not available at all of these hospitals. Therefore, we established a Kanazawa mobile embolectomy team (KMET), which could travel to these hospitals and perform the acute reperfusion therapy. In this article, we report early treatment outcomes and validate the effectiveness of a network between affiliated hospitals and KMET. Between January 2014 and December 2015, 48 patients, aged 45–92 years (mean: 73.0 years), underwent acute reperfusion therapy provided by KMET in 10 affiliated hospitals of Kanazawa University Hospital. The pre-treatment NIHSS scores ranged from 5 to 39 (mean: 19.1). ASPECTS+W ranged from 1 to 11 (mean: 7.3). Successful revascularization, defined as thrombolysis in cerebral infarction (TICI) 2b or 3, was achieved in 38/48 cases (80%), and a good outcome, defined as modified Rankin Scale (mRS) score from 0 to 2 at 90 days after the treatment, was achieved in 24/48 cases (50%). There were two cases of intracranial bleeding (4%). Mean time from onset to recanalization was 297 min. These results, which are similar to those of five previous RCTs, suggest that a collaborative network between affiliated hospitals and KMET is effective for acute reperfusion therapy in local areas wherein experienced neuroendovascular specialists are insufficient. PMID:27725522

  3. Can the use of low-dose dopamine for treatment of acute renal failure be justified?

    PubMed

    Burton, C J; Tomson, C R

    1999-05-01

    The use of dopamine for the prevention and treatment of acute renal failure is widespread. Its use is based on physiology suggesting selective renal vasodilation when it is infused at low dose. This article reviews the available data on the clinical use of dopamine. When used to prevent acute renal failure in high-risk treatments there is no evidence of benefit of dopamine but, given the low incidence of significant renal failure, the studies are underp