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At least 451 records · Page 25Linked to original sources
PubMed2005

Discovery of ligands by a combination of computational and NMR-based screening: RNA as an example target.

NMR for screening of knowledge-based focused libraries of compounds provides an efficient, cost-effective method to develop promising drug leads that target functionally important RNA structures. A knowledge-based focused library may be constructed from virtual (i.e., computational) screening of commercial or proprietary databases of available compounds for binding to the three-dimensional structure of a selected RNA target. Alternatively, the library may be constructed from compounds with properties deemed desirable, e.g., molecular moiety commonly found in drugs or known to bind RNA. The library ideally should be composed of small water-soluble, nonpeptide, nonnucleotide organic compounds. Various simple, robust NMR experiments are described that enable experimental screening of such a library for binding to a selected RNA structure. Some of the NMR experiments enable rapid mapping of the interaction site on the RNA to verify that the targeted structure is hit rather than the double helical region or a commonly occurring tetraloop. Other experiments enable elucidation of the ligand's binding moiety. Of course, any compounds thus identified should represent promising scaffolds suitable for easy chemical modification to enhance their pharmaceutical properties for subsequent drug development.

Computational Biology↗
PubMedDate not supplied

Solution- and solid-phase parallel synthesis of 4-alkoxy-substituted pyrimidines with high molecular diversity.

A simple and straightforward methodology toward the synthesis of novel 2,6-disubstituted-4-alkoxypyrimidine derivatives of type 16 and 19 has been developed. This methodology, initially developed in solution, can be perfectly adapted to the solid support under analogous conditions, taking full advantage of automated parallel synthesis systems. This successful methodology benefits from the key role played by the thioether linkage placed at the 2-position in 3, 9, or 13 in a double manner: on one side, the steric effect exerted by the thioether linkage is likely to be responsible for the very high observed selectivity toward the formation of the O-alkylation products. On the other side, this sulfur linkage can serve not only as a robust point of attachment for the heterocycle, stable to a number of reaction conditions, but also as a means of introducing a new element of diversity through activation to the corresponding sulfone (safety-catch linker concept) and subsequent ipso-substitution reaction with a variety of different N-nucleophiles.

Journal Article↗
PubMed2005

Molecular applications of the intermediate Hamiltonian Fock-space coupled-cluster method for calculation of excitation energies.

The intermediate Hamiltonian Fock-space coupled-cluster (FS-CC) method with singles and doubles is applied to calculate vertical excitation energies (EEs) for some molecular systems. The calculations are performed for several small molecules, such as H2O, N2, and CO, and for larger systems, such as C2H4, C4H6, and C6H6. Due to the intermediate Hamiltonian formulation, which provides a robust computational scheme for solving the FS-CC equations, and the efficient factorization strategy, relatively large basis sets and model spaces are employed permitting a comparison of the calculated vertical EEs with the experimental data.

Journal Article↗
PubMed2006

Customised birthweight: coefficients for an Australian population and validation of the model.

BACKGROUND: Published birthweight references in Australia do not fully take into account constitutional factors that influence birthweight and therefore may not provide an accurate reference to identify the infant with abnormal growth. Furthermore, studies in other regions that have derived adjusted (customised) birthweight references have applied untested assumptions in the statistical modelling. AIMS: To validate the customised birthweight model and to produce a reference set of coefficients for estimating a customised birthweight that may be useful for maternity care in Australia and for future research. METHODS: De-identified data were extracted from the clinical database for all births at the Mater Mother's Hospital, Brisbane, Australia, between January 1997 and June 2005. Births with missing data for the variables under study were excluded. In addition the following were excluded: multiple pregnancies, births less than 37 completed week's gestation, stillbirths, and major congenital abnormalities. Multivariate analysis was undertaken. A double cross-validation procedure was used to validate the model. RESULTS: The study of 42,206 births demonstrated that, for statistical purposes, birthweight is normally distributed. Coefficients for the derivation of customised birthweight in an Australian population were developed and the statistical model is demonstrably robust. CONCLUSIONS: This study provides empirical data as to the robustness of the model to determine customised birthweight. Further research is required to define where normal physiology ends and pathology begins, and which segments of the population should be included in the construction of a customised birthweight standard.

Australia↗
PubMed1998

Neuroendocrine and hypothermic effects of 5-HT1A receptor stimulation with ipsapirone in healthy men: a placebo-controlled study.

The neuroendocrine effects of 5-hydroxytryptamine-1A (5-HT1A) receptor stimulation remain uncertain in humans, in respect to both anterior and posterior pituitary hormone release. This is important because these endocrine responses are often used as indications of 5-HT1A receptor sensitivity. The link between receptor stimulation and subsequent hormone release is more direct with posterior pituitary hormones because there is no intermediate hypothalamic peptide in the pathway. Theoretically, therefore, posterior pituitary hormones should be more valid indicators of central 5-HT1A receptor sensitivity. We used the 5-HT1A receptor partial agonist ipsapirone (20 mg) as an oral serotonergic challenge drug in a random-order, double-blind placebo-controlled study of 12 healthy men. Blood sampling occurred at 30 min intervals up to 180 min after the administration of drug or placebo. Ipsapirone caused clear and significant elevations in adrenocorticotrophin (ACTH), cortisol (CORT), prolactin (PRL), and growth hormone (GH) release. Peak hormone and ipsapirone blood levels both occurred at 60 min after ipsapirone administration. Release of the posterior pituitary hormone oxytocin was also stimulated, but less robustly and with more baseline variation. Temperature fell significantly more after ipsapirone than placebo. These results contrast with previous studies, which found no effect of ipsapirone on PRL and GH release in humans, but are in accordance with data using other 5-HT1A agonist drugs. The presence of an oxytocin response to ipsapirone suggests that oxytocin is a potential marker for serotonergic function in neuroendocrine challenge studies, but this awaits further study.

Administration, Oral↗
PubMed2004

Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder.

BACKGROUND: Tryptophan depletion studies have suggested that central serotonin (5-hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion, could reverse the therapeutic effect of the SSRIs in social anxiety disorder (SAD) patients. METHODS: Fourteen patients with SAD who showed sustained clinical improvement with SSRI treatment underwent tryptophan depletion in a double-blind, placebo-controlled, crossover design, over 2 days 1 week apart. At the peak time of depletion, the participants also underwent three behavioral challenges: autobiographical script, verbal task, and neutral script. Psychological outcome was assessed with the Spielberger State Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring anxiety, depression, and somatic symptoms. RESULTS: Anxiety was significantly increased on the depletion day compared with the control day, both on the STAI Form Y-1 and composite VAS score. Furthermore, there was a significant depletion x time interaction, explained mainly by the anxiogenic effect of the autobiographical script. In contrast, the verbal and the neutral tasks failed to differentiate between depletion and placebo. CONCLUSIONS: Tryptophan depletion induced significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script. This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task.

Adult↗
PubMed2004

Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol: a double-blind and randomized study.

RATIONALE: There are few data from systematic, double-blind clinical trials that have compared the effect of the typical and the atypical antipsychotics on serum prolactin (PRL) levels in patients with schizophrenia. OBJECTIVES: The goal of this study was to compare the effect of risperidone and haloperidol on serum PRL and investigate the relationship between serum PRL levels and clinical response in patients with schizophrenia. METHODS: Seventy-eight inpatients with a diagnosis of schizophrenia (according to DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol after a 2-week washout period, using a randomized, double-blind design. Clinical efficacy was determined using the positive and negative syndrome scale (PANSS). Their serum PRL was assayed by means of radioimmunometric assay (RIA) between pre-treatment and post-treatment, and compared with 30 sex-matched and age-matched normal subjects. RESULTS: Both risperidone and haloperidol treatment significantly increased serum PRL levels in drug-free chronic schizophrenia patients (both P<0.001). Hyperprolactinemia induced by risperidone 6 mg/kg was comparable to levels produced by haloperidol 20 mg/day. Considering dose-adjusted serum PRL levels, risperidone treatment induced a significant elevation of PRL levels compared with haloperidol treatment at the haloperidol equivalent (P<0.001). Change in PRL levels at pre-treatment and post-treatment were related to positive symptom improvement seen in the risperidone group (r=0.51, P=0.016), but not in the haloperidol group (P>0.05). Female patients showed both a higher baseline and post-treatment PRL level and a greater increase in PRL than men (all P<0.05). CONCLUSIONS: Risperidone is associated with a robust effect on prolactin secretion in contrast to the conventional antipsychotic haloperidol. Prolactin monitoring during risperidone treatment should be performed.

Adult↗
PubMed2004

Ape1 abasic endonuclease activity is regulated by magnesium and potassium concentrations and is robust on alternative DNA structures.

Abasic lesions are common mutagenic or cytotoxic DNA damages. Ape1 is the major human apurinic/apyrimidinic (AP) endonuclease and initiates repair of abasic sites by catalyzing strand cleavage at the lesion. I show here that Ape1 single-stranded (ss) AP site incision activity prefers 0.5 mM or 2 mM MgCl(2) and low concentrations (< or =50 mM) of KCl, whereas its double-stranded (ds) activity favors 10 mM MgCl(2) and 50 mM KCl or 2 mM MgCl(2) and 200 mM KCl. Both activities favor a pH between 7.0 and 7.5, suggesting a common catalytic mechanism. In conditions designed to mimic the intracellular environment (pH 7.2; 100 mM KCl; 1 mM MgCl(2)), Ape1 ssAP site incision activity is either about fivefold more active or approximately 20-fold less efficient than its ds activity, depending on the oligonucleotide employed. Secondary structure predictions suggest a role for the DNA conformational state in determining the effectiveness of Ape1. Ape1 complex stability in the presence of EDTA (non-incising conditions) is significantly weaker for ssDNA than dsDNA, regardless of the AP substrate. Duplexes where the AP site is positioned opposite the 3' terminus of a complementary primer strand are incised with an efficiency similar (less than twofold difference) to that of the ssAP substrate alone. Moreover, Ape1 cleaved AP sites in fork-like and bubble DNA structures with an efficiency that is identical or up to sevenfold higher than ssAP-DNA. The findings here suggest that Ape1 ssAP and dsAP endonuclease activities are regulated by sequence context and the relative concentrations of certain chemical elements in vivo, and that Ape1 incision activity occurs on complex replication, recombination, and/or transcription DNA intermediates.

DNA↗
PubMed2001

Treating the substance-abusing suicidal patient.

Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population. Indeed, suicidality (ideation or behavior) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse. Consequently, to date, little is known about the optimal treatment of this population. The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s. This study involved 12 patients, all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt. The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms (including suicidal ideations) and level of drinking. However, substantial residual depressive symptoms and drinking persisted at the end of the trial. Also, because no placebo control group was utilized, the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect. To date, only one double-blind, placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients. The study involved 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. The results of that double-blind, placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. To date, no other double-blind, placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings. Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients.

Adult↗
PubMed2001

Brachyury (T) gene expression and notochord development in Oikopleura longicauda (Appendicularia, Urochordata).

Appendicularia (Larvacea) is a subgroup of Urochordata (Tunicata) comprised of holoplanktonic organisms that retain their tailed architecture throughout their life history, while other tunicates, including ascidians and doliolids, resorb the tail after metamorphosis. In order to investigate the characteristics of the appendicularian unresorbed notochord, we isolated a partial genomic clone and a full-length cDNA sequence homologous to the mouse Brachyury (T) gene from the appendicularian Oikopleura longicauda. Brachyury is known to be predominantly expressed in the notochord cells and plays an important role in their differentiation in other chordates. While phylogenetic analysis robustly supports the orthology of the isolated Brachyury gene, the exon-intron organization found in the genomic clone was distinct from that well-conserved among other T-box genes. In addition to a detailed observation of notochord development in living specimens, whole-mount double in situ hybridization was carried out using a Brachyury probe along with a muscle actin probe. The Brachyury transcripts were found in the notochord of the tailbud embryos and persisted into later stages. The present study highlights characteristics of notochord development in the appendicularian. Furthermore, these results provide basic knowledge for comprehensive understanding of the cellular- and molecular-based mechanisms needed to build the characteristic cytoarchitecture of notochord that varies among tunicate species.

Amino Acid Sequence↗
PubMed1996

Enhanced response to repeated d-amphetamine challenge: evidence for behavioral sensitization in humans.

Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent, enduring, and progressively more robust behavioral response. This process serves as an important model of neural plasticity and has also been proposed as a model for a variety of psychiatric syndromes; however, there are no published controlled studies of behavioral sensitization in human subjects. The authors report results from a double-blind, placebo-controlled study of repeated d-amphetamine challenges in a sample of normal human volunteers. Eleven consecutively recruited normal volunteers participated in this 4-day protocol. Each subject received two daily doses of d-amphetamine (0.25 mg/kg) separated by 48 hours that alternated with two daily doses of matched placebo. Symptoms (activity/energy level, mood, rate, and amount of speech) and eye-blink rates were measured hourly for 5 hours following drug administration. All four measures demonstrated significantly enhanced increases following the second amphetamine dose as compared to the first amphetamine dose and both placebo conditions. These findings suggest that behavioral sensitization is measurable in human subjects.

Administration, Oral↗
PubMed2006

Infliximab use in luminal Crohn's disease.

Infliximab has been available in the United States and Europe for more than 6 years, and its use has revolutionized the care of patients who have CD. It is used effectively for both the induction and maintenance of remission in patients who have CD and is efficacious in patients who have steroid-dependent/refractory CD and those who have fistulizing CD. Clinical trials and practice have shown infliximab to be safe, effective, and generally well tolerated. The ACCENT I and ACCENT II trials defined the best dosing and schedule regimens for its administration. With up to 30% of patients not responding to infliximab therapy, much attention has been devoted to identifying risk factors that could allow optimization of response rates. Parsi and colleagues and Arnott and colleagues demonstrated that nonsmoking and the concurrent use of immunomodulators are predictors of response to infliximab. Research has also focused on identifying biologic and immunologic markers that may correlate with response to infliximab. To date, N0D2/CARD15, anti-Saccharomyces cerevisiae antibody (ASCA), and antineutrophil cytoplasmic antibody (ANCA) have not been shown to be predictive of outcome with infliximab treatment for CD. Gene polymorphisms also are being studies with the hope that knowing the patient's genotype may help predict the course or severity of the disease, including the presence of extraintestinal manifestations, response to treatments, and susceptibility to toxicities. No single variable, however, has been consistently demonstrated to be a predictor of response to infliximab. The formation of ATIs in a small number of patients creates a clinical dilemma. ATIs have been associated with an attenuated response or loss of response to the medication over time and the development of both acute and delayed infusion reactions that occasionally are severe enough to lead to discontinuation of the medication. In such patients physicians are often left to ponder what therapy to try next. Adalimumab, a fully human monoclonal antibody used for treating rheumatologic conditions, has been investigated as an alternate treatment for patients who have CD who, after initially responding to infliximab, experience intolerance or loss of efficacy. Two studies have examined the use of adalimumab in patients who have active CD who had lost response to or developed intolerance to infliximab. In both these studies adalimumab was well tolerated and seemed to be a clinically beneficial option for such patients. Confirmation of these findings with ongoing randomized, double-blind, placebo-controlled trials is needed, however. The limits of conventional treatment for CD can be seen as a positive evolutionary force favoring the development and use of advanced therapies. The acceptance of antimetabolites began with data published a quarter-century ago and became robust in the past 5 to 10 years. Biologic therapy has become the standard of care at a far faster rate. The success seen with infliximab has broadened the acceptance of biologic therapy among professional peers, patients, and pharmaceutical developers. The lessons learned in the years since infliximab's arrival show the importance of long-term data in revealing important toxicities and best practices for maintenance. Tempered by this experience, the short cycle from concept to drug production possible with biologic therapies should bring even more advanced treatments to patients quickly while investigators work to find a cure.

Anti-Inflammatory Agents↗
PubMed2004

Dissecting nonverbal auditory cortex asymmetry: an fMRI study.

The purpose of this study was to find a robust nonverbal paradigm to obtain reliable, reproducible auditory activation and characterize the nonverbal activation of the auditory cortex in regard to the Brodmann regions. The extent of localization and lateralization of activation was investigated utilizing functional magnetic resonance (fMR). Two tasks were used: monotonous repetitive stimuli of "double octaves" (DO) consisting of alternating four A with four C piano notes and a variated string of "sequential notes" (SN), which was a fast nonrepetitive sequence of piano notes. Eleven volunteers were investigated. The activation periods had a duration of 30 s, and presented every 30 s. All subjects demonstrated fMRI signal activity in the superior temporal gyrus (STG) involving the primary and secondary auditory cortex except one subject who showed no activation with the DO stimulus. SN elicited more activation than DO (p =<.03). The bulk activation for SN and DO was slightly greater in the right hemisphere, although the primary auditory area (Brodmann's 41) was better activated on the left p =<.001. Brodmann's area 22 was most frequently right-side dominant (p =.015, p =.017 for DO and SN, respectively). These findings appear to have implications in the examination of preverbal subjects.

Acoustic Stimulation↗
PubMed2004

Real-time PCR genotyping using displacing probes.

Simple and reliable genotyping technology is a key to success for high-throughput genetic screening in the post-genome era. Here we have developed a new real-time PCR genotyping approach that uses displacement hybridization-based probes: displacing probes. The specificity of displacing probes could be simply assessed through denaturation analysis before genotyping was implemented, and the probes designed with maximal specificity also showed the greatest detection sensitivity. The ease in design, the simple single-dye labeling chemistry and the capability to adopt degenerated negative strands for point mutation genotyping make the displacing probes both cost effective and easy to use. The feasibility of this method was first tested by detecting the C282Y mutation in the human hemochromatosis gene. The robustness of this approach was then validated by simultaneous genotyping of five different types of mutation in the human beta-globin gene. Sixty-two human genomic DNA samples with nine known genotypes were accurately detected, 32 random clinical samples were successfully screened and 114 double-blind DNA samples were all correctly genotyped. The combined merits of reliability, flexibility and simplicity should make this method suitable for routine clinical testing and large-scale genetic screening.

Amino Acid Substitution↗
PubMed2000

Spatiotemporal stability of one-way open coupled nonlinear systems

The present paper investigates the spatiotemporal stability of homogeneous solutions in one-way open coupled nonlinear systems. We show that the H(infinity) norm concept, which has been used as an important index in the field of robust control theory, allows us to grasp the mechanism of spatial instability in coupled systems. Spatial instability occurs only when the H(infinity) norm of the transfer function of each site is greater than 1. It is shown that numerical simulations for one-way open coupled double scroll circuits are in good agreement with our theoretical results.

Journal Article↗
PubMed2006

A population coding account for systematic variation in saccadic dead time.

During movement programming, there is a point in time at which the movement system is committed to executing an action with certain parameters even though new information may render this action obsolete. For saccades programmed to a visual target this period is termed the dead time. Using a double-step paradigm, we examined potential variability in the dead time with variations in overall saccade latency and spatiotemporal configuration of two sequential targets. In experiment 1, we varied overall saccade latency by manipulating the presence or absence of a central fixation point. Despite a large and robust gap effect, decreasing the saccade latency in this way did not alter the dead time. In experiment 2, we varied the separation between the two targets. The dead time increased with separation up to a point and then leveled off. A stochastic accumulator model of the oculomotor decision mechanism accounts comprehensively for our findings. The model predicts a gap effect through changes in baseline activity without producing variations in the dead time. Variations in dead time with separation between the two target locations are a natural consequence of the population coding assumption in the model.

Action Potentials↗
PubMed2006

Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial.

The aim was to evaluate the efficacy and safety of two recombinant factor VIIa (rFVIIa) dose regimens for treating haemarthroses in patients with congenital haemophilia A or B and inhibitors. This was a multicentre, randomised, cross-over, double-blind trial. Patients were randomly allocated to treat a first joint bleeding episode with one 270 microg/kg rFVIIa dose followed by two doses of placebo at 3-hour intervals and a second joint bleed with three single doses of 90 microg/kg rFVIIa at 3-hour intervals, or vice versa. Efficacy was evaluated using a novel and robust treatment response-rating scale based on patient-assessment of pain and joint mobility. Outcome was rated at different timepoints, and an effective or ineffective treatment response was determined. Treatment "preference" was defined as effective treatment with one regimen and ineffective with the other. Patients with equally effective or ineffective treatments had no "preference". Treatment was rated as effective for 65% of patients using the 270 microg/kg dose versus 70% for the 90 microg/kg x 3 regimen. An equal "preference" was noted for the two regimens (21% for each; p = 0.637); most patients (58%) had no "preference". 37/42 bleeding episodes (88%) were successfully treated with rFVIIa; additional haemostatic medications were administered for five episodes. No safety issues were identified. Administration of rFVIIa as a single 270 microg/kg dose to treat haemarthroses in patients with haemophilia and inhibitors was at least as efficacious and safe as the 90 microg/kg x 3 regimen.

Adolescent↗
PubMed2002

SSRI treatment of borderline personality disorder: a randomized, placebo-controlled clinical trial for female patients with borderline personality disorder.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are recommended for treatment of affect lability, impulsivity, and aggression in patients with borderline personality disorder. This recommendation is based on positive findings in at least 10 open studies and one small double-blind study of SSRIs for patients with borderline personality disorder and one study of impulsive aggressive patients with different personality disorders. A randomized, placebo-controlled SSRI study with borderline personality disorder patients, however, provided inconclusive results because of a large response to placebo. It was, therefore, decided to conduct a new randomized trial with a larger study group. METHOD: A double-blind, placebo-controlled, randomized trial using the SSRI fluvoxamine for 6 weeks followed by a blind half-crossover for 6 weeks and an open follow-up for another 12 weeks was conducted with 38 nonschizophrenic, nonbipolar female patients with borderline personality disorder. The outcome measures were the rapid mood shift, impulsivity, and aggression subscales from the Borderline Personality Disorder Severity Index. RESULTS: Fluvoxamine but not placebo produced a robust and long-lasting reduction in the scores on the subscale for rapid mood shifts. In contrast, no difference between the fluvoxamine and placebo groups was observed in the effect on the impulsivity and aggression scores. CONCLUSIONS: In this study, fluvoxamine significantly improved rapid mood shifts in female borderline patients, but not impulsivity and aggression. This latter finding may be due to gender-specific differences in impulsivity and aggression.

Adolescent↗