Although the process of reconstruction is identical for prokaryotic and eukaryotic metabolic networks, the authors emphasize that in eukaryotic systems, e.g., metabolism of higher plants, it is more challenging due to the size of genomes and cellular compartmentation [46]. Additional complexity arises from network gaps and mass-balance errors resulting from incomplete genome annotation and reaction stoichiometry errors which severely affect the Inhibitors,research,lifescience,medical predictive power of network models [47]. Beyond that, model

simulations provide only information about a steady state, i.e., a snapshot, of the system, which is pre-defined by the experimental design. Recently, in several studies genome-scale metabolic modeling in Arabidopsis

thaliana was applied to address questions like ATP demand for growth Inhibitors,research,lifescience,medical and maintenance [21], the metabolic activity of key enzymes responsible for the supply of redox equivalents in plastids during the photorespiratory cycle [48] or to predict the design of genetic manipulations that are expected to increase vitamin E content in metabolically engineered Inhibitors,research,lifescience,medical seed strains [49]. With respect to such comprehensive metabolic network simulations, quantitative measurement of metabolism is necessary to validate the output of such simulations, which can be accomplished applying bioanalytical Selleck GSK2656157 methods in metabolomics science [50]. Mass spectrometry is one of the crucial technologies in this field, Inhibitors,research,lifescience,medical and an overview of different techniques in context with their characteristic features has recently been presented [32]. A recent development is the use of two-dimensional gas chromatography coupled with fast acquisition rate time-of-flight mass spectrometry (GC x GC-TOF-MS). Inhibitors,research,lifescience,medical The coupling of two gas chromatography columns with different characteristics, for

example a hydrophobic and a polar column, increases the separation efficiency of a complex metabolomics sample. A complete strategy to perform a convenient data extraction and alignment using two-dimensional gas chromatography coupled with mass spectrometry (GC x GC-MS) technology is already available [51]. Another important extension of current metabolomics Cell press platforms for metabolomics is the integration of gas chromatography coupled to mass spectrometry (GC-MS) with liquid chromatography coupled to mass spectrometry (LC-MS) [52]. This approach enables the analysis of components of the primary metabolism by GC-MS, for example carbohydrates and amino acids, and higher molecular masses by LC-MS, e.g., secondary metabolites [53,54]. Beyond the development of techniques and new platforms, the improvement of databases, experimental standards and data compatibility among different laboratories is crucial for efficient metabolomics science [55].

Conclusion We tried to influence muscle hypertonia, defined clinically as resistance to passive movements of extremities or their parts. The Selleckchem PD 332991 author first refers to hypertonus of central origin which we tried to suppress by subarachnoidal application of phenol, and later on by low frequency electrostimulation according to Hufschmidt’s system. Positive effects on Parkinsonian rigidity and akinesia were found as well. The adapted technique was applied with good results even on retention and incontinence of urine. For the first time, a syndrome of transient painful

cramps of peripheral genesis was differentiated as a hereditary disease without the possibility of being improved. Inhibitors,research,lifescience,medical At the same time, we developed ischemic and hyperventilation tests for chronic tetany, applying them to different conditions. The resistance in dystrophic myotony was reduced by carbamazepine or Lignocaine with unchanged spontaneous EMG activity.

As early as 1982, we differentiated a patient with neuromyotonia, whose symptoms were reduced by carbamazepine; Inhibitors,research,lifescience,medical they then completely disappeared on corticosteroids. Patients with neuromyotonia kept appearing. We differentiated a new neurological symptom of subacute contracture Inhibitors,research,lifescience,medical of fingers that disappeared very quickly on ulnar nerve neurolysis. In three unrelated patients, we differentiated slowly progressive Inhibitors,research,lifescience,medical contracture of the spine with proximal myopathy, and, until then not described, a syndrome of hereditary progressive contracture of fingers accompanied by extreme muscle percussion symptom and special repetitive EMG activity. In one patient, with spinal MR pathology the frequent, very painful paroxysmal, generalised spasms disappeared fully on corticosteroids. All these significant results were the consequence of steady application Inhibitors,research,lifescience,medical of the basic rules cited above: watch, listen and use your own common sense

and experience; ask questions and compare!
Glycogenosis II (GSD II) is an autosomal recessive lysosomal storage disorder resulting from acid alpha-glucosidase deficiency, subsequent accumulation of glycogen in tissues, impairment Linifanib (ABT-869) of autophagic processes and progressive cardiac, motor and respiratory failure. The late-onset form is characterized by wide variability in residual enzyme activity, age of onset, rate of disease progression and phenotypical spectrum. Although the pathological process mainly affects the skeletal muscle, several other tissues may be involved in the course of the disease; therefore GSD II should be regarded as a multisystem disorder in which glycogen accumulation is present in skeletal and smooth muscle, heart, brain, liver, spleen, salivary glands, kidney and blood vessels. In this review, we briefly summarize the main non-muscle targets of the pathological process in late-onset GSD II.

The frontal cortex receives the largest portion of BG outputs (via the thalamus), suggesting a close collaboration between the BG and frontal cortex.23,24 DA acts not only on the PFC but

also on the BG. Importantly, the DA projections into the striatum (the input to the BG where cortical information converges) are much heavier than those to the PFC.25 Thus, DA teaching signals may play a stronger role in gating plasticity in the striatum in contrast to the PFC, where DA influence may be more subtle—shading, not gating, plasticity. This may explain our observation that during operant learning, learning-related changes in the striatum appear sooner and faster than those in the PFC.26 Thus, the trade-off Inhibitors,research,lifescience,medical between the advantages of slow plasticity versus fast plasticity may play out in interactions between the PFC and BG.27 The idea is that during learning, specific associations between cues and immediate actions are quickly acquired by the striatum, by virtue of its heavy inputs from midbrain DA neurons. The output of the basal ganglia trains the PFC26 where plasticity is “slower” (smaller changes Inhibitors,research,lifescience,medical in synaptic weights with each learning episode) because of the weaker DA influence. As a result, the PFC gradually builds up less error-prone, more elaborate, and generalized representations Inhibitors,research,lifescience,medical based on the patterns fed

to it by the BG. This may explain why the PFC and BG seem to operate based on different types of representational schemes.28 The fast striatal plasticity may be more suited for Inhibitors,research,lifescience,medical a quick stamping-in

of immediate, direct associations. But, as a consequence, the striatum learns complex behaviors in a piecemeal fashion, as a set of largely unconnected (cache) representations of which alternative was more successful at each decision Inhibitors,research,lifescience,medical point in the task.28 By contrast, the slow PFC plasticity may be suitable for building elaborate rule representations that gradually link in more information (ie, tree-like representations).28 The slow PFC plasticity may also find the commonalities and regularities among the simpler representations acquired by the striatum that are the basis for abstractions and general principles.29 In other words, the striatum learns the pieces of the Doramapimod puzzle while the PFC puts the puzzle together. 27 We recently witnessed this hand-off from the striatum to PFC as animals transitioned Thiamine-diphosphate kinase from simple, specific learning to more generalized, abstract representation.30 Each day, monkeys learned to associate two novel, abstract, dot-based categories with a right vs left saccade (Figure 3). At first, monkeys only saw a few examples of each category, and they could learn specific stimulus-response (S-R) associations by rote. But as more and more new category exemplars were added, the capacity to memorize specific S-R associations was exceeded. To solve the task, the monkeys then had to learn the categories, and extract the common essence that united exemplars from the same group.

2 The article by Hoebeke and colleagues reviews methods

for assessment of children with Romidepsin in vitro daytime urinary incontinence using evidence from the literature and assembling it in this standardized document.1 The article emphasizes the importance of taking an accurate medical history and questioning the child when possible. They suggest that, although experienced practitioners treating children with lower urinary tract dysfunction can usually diagnose their problems, others may prefer to use scoring systems such as that by Akbal and colleagues.3 A voiding diary of fluid intake and output during a 24-hour period as well as keeping track of urinary frequency and voided volumes can be useful. A similar chart should Inhibitors,research,lifescience,medical be kept for bowel habits. The physical examination should determine if bladder distension or fecal impaction Inhibitors,research,lifescience,medical is present. Also, neurologic testing will assess the integrity of sacral segments. Noninvasive testing includes a renal/bladder ultrasound and uroflow studies. The authors indicate that residual urine > 10% of the expected bladder capacity for age (in cc) is significant. The ultrasound also provides information on the presence of constipation. A bladder Inhibitors,research,lifescience,medical base impression and rectal width > 3 cm in the absence of an urge to have a bowel movement is a significant indicator of constipation. When there is significant

urinary frequency and irritative symptoms, a urinalysis is recommended not only to assess for Inhibitors,research,lifescience,medical urinary tract infection (UTI) but also for pH and calcium content because the group from Vanderbilt has reported hypercalciuria in a subgroup of dysfunctional voiding syndromes in childhood.4 The uroflowmetry measures the urinary stream during voiding and quantifies the volume voided over a unit of time.1 The

Inhibitors,research,lifescience,medical Qmax refers to the peak or maximal flow rate in milliliters per second and the Qave reflects average flow per unit of time. Generally, Qave is usually > 50% but < 85% of the Qmax value. The uroflow curve is normally bell shaped in all healthy children, but will change when the voided volume is < 50% of the expected bladder capacity for age. The authors note that the uroflow studies may help identify those who need video-urodynamic studies. The authors propose that patients with thick-walled Calpain bladders on ultrasound and obstructed flow patterns and dilated lower ureters may have reflux or poor compliance. These patients, in addition to those who have failed all conventional therapy, should undergo video-urodynamic studies. They stress in their article that the voiding cystourethrogram should not be part of the routine assessment of most children with urinary incontinence. Forthcoming reports from the ICCS will discuss effective treatments for daytime incontinence. The second article by Nevéus and colleagues discusses recommendations for treating children with monosymptomatic nocturnal enuresis (MNE).

Symptoms tend to resolve spontaneously around puberty. Myopathy often appears in adult life, long after liver symptoms have subsided. Adult-onset myopathies have been distinguished into two groups, distal and generalized (31). Patients with distal myopathy develop atrophy of leg and intrinsic hand muscles, often suggesting the diagnosis of motor neuron disease or peripheral #Sorafenib in vitro keyword# neuropathy (32). The course is slowly progressive and

the myopathy is rarely crippling. Patients with generalized myopathy are more severely affected and often suffer from respiratory distress (31, 33). Although debrancher works in parallel with myophosphorylase, the symptoms of debrancher deficiency are very Inhibitors,research,lifescience,medical different from those of McArdle disease and cramps and myoglobinuria are exceedingly

rare. One reason for this discrepancy may be that in McArdle disease glycogen cannot be broken down at all, whereas in GSD III, the most peripheral portions of normal glycogen can be utilized, as shown by lactate production in vitro (Fig. ​(Fig.4).4). However, for this minor “spare fuel” to work in vivo, one has to postulate a constant recycling of the peripheral chains between glycogen and PLD, while most of the stored glycogen in GSD Inhibitors,research,lifescience,medical III appears to be in the form of PLD. Figure 4 Comparative lactate production through anaerobic glycolysis in vitro by muscle homogenates from normal controls, 3 patients with debrancher deficiency (P1, P2, P3) and one patient with McArdle disease. A more important explanation for the fixed, and mostly distal, weakness is the simultaneous involvement of muscle and nerve, as clearly documented both electrophysiologically and by nerve Inhibitors,research,lifescience,medical biopsy (34, 35). Although the glycogenoses have been studied for almost one century (29), this Symposium documents how new enzyme defects are still

being discovered, clinical variants of known defects are being described, pathogenetic mechanisms are incompletely understood, molecular studies have not provided clear genotype/phenotype relationships, and therapy is still woefully inadequate. Clearly, much remains to be done. Acknowledgements Inhibitors,research,lifescience,medical Part of this work has been supported by a grant from the Muscular Dystrophy those Association.
Glycogen storage disease type II (GSD-II), also known as Pompe disease, or acid maltase deficiency (AMD), is an autosomal recessive genetic disorder that encompasses a range of clinical phenotypes, but myopathy is common to all. This “variable expressivity” manifests primarily as variances in age of onset of disease symptoms, as well which organs are pathologically involved. The most severe form of GSD-II is the infantile-onset form, and was originally described by Dr. Pompe. These severely affected infants may appear normal at birth, but soon develop generalized muscle weakness and cardiac myopathy manifesting initially as a hypertrophic cardiomyopathy.

A candidate mechanism in the development of substance dependence is the failure of top-down systems of self-regulation and effortful processing, particularly frontoparietal networks, to override subcortical

networks involved in habitual responses to reward cues, which are strengthened with accumulated exposure to drug cues and consumption (Koob 2006; Koob and Volkow 2010). Given the age range of our sample (ages 21–56), it is important to recognize that changes in FA and downstream changes in the function of neural networks may begin relatively early in the trajectory of problem drinking. Lower FA consistently Inhibitors,research,lifescience,medical showed significant correlations with greater BOLD activity in the thalamus, medial frontal gyrus, cingulate, and parahippocampal gyrus. One interpretation of this see more pattern is that individuals exhibit greater cue reactivity when bottom-up activity originating in the thalamus guides subsequent attentional orienting and salience attribution in the prefrontal cortex and limbic system. A great body of literature has demonstrated the role of prefrontal

cortex and cingulate Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical in affective and reward-related decision making (Bechara et al. 1998; Bechara 2004; Rogers et al. 2004; Cohen et al. 2005). Because participants were not engaged in a decision-making task, it remains unknown how increased cue reactivity might affect these processes. However, one hypothesis for future study is that lower integrity of frontoparietal white matter networks mediates the relationship between increased cue reactivity and alcohol urges. It should be noted that white matter fiber tracts are largely bidirectional Inhibitors,research,lifescience,medical and that analyses did not investigate the temporal sequence of activation. Thus, an alternative mechanism that might operate instead of or in conjunction with weakened top-down control over bottom-up response is alteration of the signal communicated upward from subcortical to cortical regions as a result of changes in white matter integrity, affecting the processing of cue-eliciting Inhibitors,research,lifescience,medical stimuli. A recent meta-analysis of alcohol cue reactivity found that heavy drinkers reliably showed increased activation in the right caudate, cingulate cortex, thalamus,

and ventromedial prefrontal cortex relative to control cue conditions (Schacht et al. 2013). However, alcohol-elicited activation in these areas was not significantly greater in heavy-drinking groups compared to control Cediranib (AZD2171) groups, suggesting that the incentive salience of alcohol cues may be comparable across groups (Schacht et al. 2013). Areas that did differentiate AUD and control groups were the bilateral precuneus, left posterior cingulate, and left superior temporal gyrus. The findings of the current study converge with the meta-analytic findings, which demonstrated the importance of cue-elicited activity in posterior regions such as the precuneus and posterior cingulate in differentiating alcohol dependent from healthy individuals and varying as a function of severity.

30,31 The major metabolic pathway in the production of glutamate is derived from glucose and the transamination of α-ketoglutarate; however, a small proportion of glutamate is formed directly from glutamine.Thc latter is actually synthesized in glia, via an active process (requiring adenosine triphosphate [ATP]), and is then transported to neurons where glutaminase is able to convert this precursor to glutamate (Figure 1). Following

release, the concentration of glutamate in the extracellular space is highly regulated and controlled, Inhibitors,research,lifescience,medical primarily by a sodium-dependent reuptake mechanism involving several transporter proteins. The major glutamate transporter proteins found in the CNS include excitatory amino acid transporters Inhibitors,research,lifescience,medical (EAATs): EAAT1 (or GLAST-1), EAAT2 (or GLT-1), and EAAT3 (or EAAC1), with EAAT2 being the most predominantly expressed form in the forebrain. Additionally, these transporters are differentially expressed in specific cell types,

with EAAT1 and EAAT2 being found primarily in glial cells, EAAT3 localized in neurons, and EAAT4 mainly localized in Inhibitors,research,lifescience,medical cerebellum. The physiological events regulating the activity of the glutamate transporters are not well understood, though there is evidence that phosphorylation of the transporters by protein kinases may differentially regulate glutamate transporters and therefore glutamate reuptake (discussed in reference 30). Glutamate concentrations Inhibitors,research,lifescience,medical have been shown to rise to excitotoxic levels within minutes following traumatic or ischemic injury, and there is evidence that the function of the glutamate transporters becomes impaired under these excitotoxic conditions.32 Moreover, microdialysis studies have shown that severe stress increases extracellular levels Inhibitors,research,lifescience,medical of glutamate in hippocampus, and NMDA glutamate

receptor antagonists attenuate stress-induced atrophy of CA3 pyramidal neurons. Figure 1. Glutamatergic system. This figure depicts the various regulatory processes involved in glutamatergic neurotransmission, as described in the text. In astrocytes, glutamine can undergo oxidation to yield a-ketoglutarate, which can also be transported to … Glutamate receptor subtypes: a focus on NMDA and AMPA receptors The many subtypes of glutamatergic Olopatadine receptors in the CNS can be classified into two major subtypes – the ionotropic and metabotropic receptors (Table I). The ionotropic glutamate receptor ion channels are assemblies of homooligomeric or hetero-oligomeric subunits integrated into the neuron’s membrane. Every channel is assembled of (most likely) four subunits associated into a selleckchem dimmer of dimers, as has been observed in cristallographie studies.33,34 Every subunit consists of an extracellular amino terminal and ligand-binding domain, three transmembrane domains and a re-entrant pore loop (located between the first and second transmembrane domains), and an intracellular carboxyl terminal domain.

Attitudes and beliefs about, medication, as well as satisfaction with medications, are also important covariates of nonadherence; an example of self-report measures addressing these construct is the Drug Attitude Inventory44 and the Brief Evaluation of Medications Attitudes and Beliefs.45 Another useful assessment, tool is the AIDS Clinical Trials Group’s Adherence Measure,“46 which includes a set of questions about

reasons for nonadherence. Gathering the individual’s perspective about what causes nonadherence behaviors can be essential to formulating an intervention strategy. Risk factors for nonadherence There are multiple and interacting risk factors for medication nonadherence, Inhibitors,research,lifescience,medical with Inhibitors,research,lifescience,medical no single profile for high risk for nonadherence. Conceptually, these can be divided into patient-related, medication-related, and providerrelated risk factors.47 Most research has been focused on patient-related risk factors.48 Among patient characteristics that appear to be risk factors for nonadherence, the strongest support appears to be for comorbid substance use, younger age, lower education level, and cognitive impairment. Additionally, attitudinal factors, particularly the denial of the need for medications/severity of the illness appear to

account for a substantial proportion of variance in adherence.49 In the Health Beliefs Model, an Inhibitors,research,lifescience,medical individual is likely to engage in a behavior, such as adherence, if they believe their condition is severe enough to warrant, treatment, if the perceived benefits of treatment outweigh the drawbacks, Inhibitors,research,lifescience,medical and if cues to action are provided to initiate and maintain the behavior. It is likely that these factors change over the course of the illness. In the early stages, acceptance of the illness is lower and avoidance coping is higher,50 potentially accounting for the relationship found between younger age and worse adherence. In our work with older adults, we have hypothesized that cognitive impairment and

increasing medication burden may heighten the buy Tyrphostin AG-1478 importance of cues to action in maintaining adherence.51 Medication-related risk factors are less clear, Inhibitors,research,lifescience,medical with some studies finding that higher rates of side effects, and greater medication burden (ie, more medication and/or more frequent, dosing) related to worse adherence whereas some have found no association or the inverse.52-53 Interestingly, in a large cross-national European survey, fears about future side Oxygenase effects (eg, fear of toxicity) or dependence on medication were more related to nonadherence than were experienced side effects, which were rarely endorsed a reason for stopping medications.54 Provider-related predictors of adherence include the quality of the therapeutic alliance and satisfaction with care provided.48 Factors involved in the alliance would include the degree of agreement between in terms of treatment outcomes and importance of side effects.

De plus, l’imagerie moléculaire permet la détection de modifications fonctionnelles précédant la pathologie manifeste, ce qui est particulièrement utile pour le diagnostic précoce et le traitement des troubles du SNC. Dans cet article, nous nous intéressons à la capacité de l’imagerie moléculaire d’informer sur le développement et l’évaluation des traitements dans son application aux troubles du SNC, en particulier pour la schizophrénie, la maladie de Parkinson, la dépression et la démence, troubles majeurs du SNC. Nous analysons également la possibilité de piloter le développement de nouveaux médicaments

des troubles du SNC par l’imagerie moléculaire. Introduction Molecular Inhibitors,research,lifescience,medical imaging techniques Inhibitors,research,lifescience,medical such as positron emission

tomography (PET) and single photon CX-4945 concentration emission computed tomography (SPECT) enable the in vivo characterization and measurement of biologic processes using high-affinity and high-specificity molecular probes.1 PET and SPECT use molecules labeled with a radionuclide that emits photons, known as a radiotracer or radioligand, that are detected in the scanner to provide data on the localization of the radiolabeled molecule in the tissue of interest. As such they provide a noninvasive means of visualizing, and characterizing physiological processes in vivo and the opportunity to make discoveries in the living, intact Inhibitors,research,lifescience,medical brain. The major

differences between PET and SPECT stem from the nature of the radionuclides used to label the tracer. The most commonly used radionuclides are 99mTc, 111In, 123I and 201T1 for SPECT, and 11C, 13N, 15O, and 18F for PET. The radionuclides used for SPECT have relatively long half-lives, in Inhibitors,research,lifescience,medical the range of hours, and emit a single photon. In contrast, those used in PET have Inhibitors,research,lifescience,medical shorter half-lives, in the range of minutes to just under 2 hours in the case of 18F, and emit a positron, which annihilates when it collides with nearby electrons to emit two photons. The difference in the nature tuclazepam of photon emission leads to differences in emission detectors and image construction — SPECT uses collimation and PET uses coincidence detection. The advantages and limitations of both techniques follow from these properties — as SPECT tracers have longer half-lives they do not need an on-site cyclotron and, multiple scans are possible from one synthesis; this means they are cheaper to make than PET tracers. However, PET uses radionuclides that tend to be easily combined with biological molecules, and has better resolution. Imaging in vivo can avoid the various potential biases or confounds of ex vivo studies, such as exposure to psychotropic drugs or mis-counting object fragments in a sectioned tissue volume2 whilst also enabling molecular alterations to be linked to clinical changes.

gov Identifiers: NCT00211744 and NCT00182520). Also for pregabalin, which can indirectly inhibit glutamate release via blockade of calcium channels, beneficial effects on OCD symptoms in combination with serotonergic antidepressants have been reported in case reports.69,70 A double-blind placebo-controlled study with pregablin in SSRI-refractory OCD is being conducted (ClinicalTrials.gov Identifier: NCT00994786). For augmentation of fluoxetine in a treatment refractory patient with glutamate modulator N-acetylcysteine, a marked decrease of OCD symptoms was observed.71 A doubleblind study

with this agent is currently recruiting patients with OCD (ClinicalTrials.gov Inhibitors,research,lifescience,medical Identifier: NCT00539513). Another interesting development with a glutamatergic agent involves D -cycloserine, a partial agonist at the NMDA receptor, which was found to facilitate fear extinction learning in preclinical and human studies when administered before or shortly after exposure to fearful cues.72

Inhibitors,research,lifescience,medical D-cycloserine augmentation of psychotherapy with exposure and response prevention in OCD has so far been investigated in three randomized, double-blind, placebo-controlled studies. A study with ten exposure sessions and drug intake 4 hours before each session failed to support the use of D-cycloserine Inhibitors,research,lifescience,medical (250 mg).73 In contrast, significantly greater decreases in obsession-related distress after four exposure sessions under D-cycloserine (125 mg, given 2 hours before each session) were reported.74

However, the placebo Inhibitors,research,lifescience,medical group tended to catch up after additional sessions. Both the number of therapy dropouts and the number of sessions needed to achieve “clinical milestones” were decreased by active treatment. In another study, OCD patients were reported to be significantly more improved under D-cycloserine at mid-treatment (ten behavior therapy sessions in total, dose of 100 mg 1 hour before each session), but not at later time points.75 Dosage and timing of D-cycloserine as well as the number of combined intervensions are critical parameters. So far, just a shortterm acceleration of response to exposure therapy under D-cycloserine was shown, Inhibitors,research,lifescience,medical but no significant differences in the further course due to floor effects of exposure therapy. Several antidepressants other than SSRIs or clomipramine have been Adenosine tested, as mentioned for noradrenergic tricyclics above. For the alpha-2 receptor and serotonin (5-HT)2/3 receptor antagonist mirtazapine an open trial Bcr-Abl inhibitor showed negative results.76 However, in a double -blind discontinuation period of 8 weeks (after an open trial) superiority of to placebo was demonstrated.77 Addition of mirtazapine to citalopram did not result in increased efficacy when compared with addition of placebo, but was associated with an accelerated onset of action in a single -blind study.78 Preclinical experiments suggest that blockade of 5-HT2C receptors may have an anticompulsive effect in OCD.