“OBJECTIVE: To evaluate the applicability of low-field int

“OBJECTIVE: To evaluate the applicability of low-field intraoperative magnetic resonance imaging (iMRI) during transsphenoidal surgery AZD3965 of pituitary macroadenomas.

METHODS: Fifty-five transsphenoidal surgeries were performed for macroadenomas (modified Hardy’s Grade II-IV) resections. All of the surgical processes were guided by real-time updated contrast T1-weighted coronal and sagittal images, which were acquired with 0.15 Tesla PoleStar N20 iMRI (Medtronic Navigation, Louisville, CO). The definitive

benefits as well as major drawbacks of low-field iMRI in transsphenoidal surgery were assessed with respect to intraoperative imaging, tumor resection control, comparison with early postoperative high-field magnetic resonance imaging, and follow-up outcomes.

RESULTS: Intraoperative imaging revealed residual tumor and guided extended tumor resection in 17 of 55 cases. As a result, the percentage of gross total removal

of macroadenomas increased from 58.2% to 83.6%. The accuracy of imaging evaluatin of low-field iMRI was 81.8%, compared with early postoperative high-field MRI (Correlation coefficient, 0.677; P < 0.001). A significantly lower accuracy was identified with low-field iMRI in 6 cases with cavernous sinus invasion (33.3%) in contrast to the 87.8% found with other sites (Fisher’s exact test, P < 0.001).

CONCLUSION: The PoleStar N20 low-field iMRI navigation system is a promising tool for safe, miniamlly invasive, endonasal, transsphenoidal pituitary macroadenomas resection. It enables neurosurgeons to control the extent of tumor resection, particularly for suprasellar tumors, ensuing surgical see more accuracy and safety, and leading to the decreased likelihood of repeat surgeries. However, this technology is still not satisfying in estimating the amount of the parasellar residual tumor invading into caverrnous

sinus, given the false or uncertain images generated by low-field iMRI selleck chemicals llc in this region, which are difficult to discriminate between tumor remnant and blood within the venous sinus.”
“Chronic kidney disease is often complicated by uremic cardiomyopathy that consists of left ventricular hypertrophy and interstitial fibrosis. It is thought that hypertension and volume overload are major causes of this disease, but here we sought to identify additional mechanisms using a mouse model of chronic renal insufficiency. Mice with a remnant kidney developed an elevated blood urea nitrogen by 1 week, as expected, and showed progressive cardiac hypertrophy and fibrosis at 4 and 8 weeks even though their blood pressures were not elevated nor did they show signs of volume overload. Cardiac extracellular signal-regulated kinase (ERK) was activated in the uremic animals at 8 weeks. There was also an increased phosphorylation of S6 kinase, which is often mediated by activation of the mammalian target of rapamycin (mTOR).

0%) patients Nine (26 5%) patients received reinjection due to i

0%) patients. Nine (26.5%) patients received reinjection due to inadequate obturation as judged by EUS. There were six episodes of rebleeding in three (8.8%) patients in the MUP group. The free-of-rebleeding rate for the MUP group was significantly higher than that for the control group (p < 0.05). The cumulative PD173074 survival for the MUP group was slightly better than that

for the control group but was not statistically significant. The patients’ compliance in both groups was similar. The endosonographers considered the performance of MUP sonography to be convenient. Conclusions. MUP sonography is useful for the evaluation of the adequacy of tissue adhesive obturation of gastric varices that may reduce the probability of rebleeding. 886″
“Objective. The use of nonanesthetist-administered propofol (NAAP) in GI endoscopy has long been controversial. In the setting of NAAP, acute situations can develop during endoscopy and thus training before starting with NAAPs is considered crucial. The aim was to evaluate a pilot study on crew resource management (CRM)-based training of teams of endoscopists and endoscopy nurses in NAAP in a full-scale hybrid simulation consisting of a full-scale human patient simulator and an endoscopy simulator. Our hypothesis was that the training would increase

the self-efficacy of the participants. Material AG14699 and methods. Four scenarios were created, each with typical side effects of propofol administration.

All scenarios included the need for prompt decision-making Bcl-w and treatment. Colonoscopy, gastroscopy or endoscopic retrograde cholangiopancreatography (ERCP) cases were assigned to the course participants in coherence with their main clinical expertise in order to facilitate situated and contextualized training. Twenty-one participants (ten doctors and eleven nurses) completed a questionnaire on self-efficacy before and after the course. A questionnaire regarding the quality and yield of the course was also completed. Results. For all participants, the self-efficacy score was 26.0 (24.0-28.0; interquartile range) before training and 30.0 (27.0-30.5) after training (p = 0.0003). The ten doctors had a self-efficacy score before training of 26.5 (25.0-29.5) and 30.0 (29.0-33.0) after (p = 0.0078). The eleven nurses scored 24.0 (22.0-26.0) before and 28.0 (27.0-30.0) after training (p = 0.0098). Conclusions. Systematic target focused scenario-based training with hybrid simulation of NAAP in endoscopy resulted in increased self-efficacy in both nurses and physicians.”
“RNA viruses show enormous capacity to evolve and adapt to new cellular and molecular contexts, a consequence of mutations arising from errors made by viral RNA-dependent RNA polymerase during replication. Sequence variation must occur, however, without compromising functions essential for the completion of the viral cycle.

(C) 2010 Elsevier Ireland Ltd All rights reserved “

(C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Generalized epilepsy with febrile seizures plus (GEES+) is an epileptic syndrome inherited in autosomal dominant mode. Of all the identified Selleckchem Bleomycin causative GEFS+ genes, voltage-gated sodium channel alpha 1 subunit gene (SCN1A) is the most clinically relevant one. We describe here the clinical and molecular characterization of a GEFS+ family. A novel heterozygous mutation c.5383G>A was revealed by direct sequencing of the SCN1A

gene for both affected and unaffected individuals. It is speculated that the function of the sodium channel could be compromised by the substitution of lysine for a highly conserved residue glutamic acid at position 1795 within the C-terminus of alpha 1 subunit. Our finding extends the spectrum of SCN1A mutations related to GEFS+ and further confirms the contribution of the sodium channel genes to the etiology of idiopathic epilepsies. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The activation IACS-10759 ic50 of microglia plays an important role in a variety of brain disorders by the excessive production of inflammatory mediators

such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokines. We investigated here whether pinoresinol isolated from the fruits of Forsythia koreana Nakai inhibits the inflammatory responses in LPS-activated microglia. Pinoresinol inhibited the production of NO, PGE(2), TNF-alpha, IL-1 beta and IL-6 in LPS-activated primary microglia. Also, pinoresinol attenuated mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in LPS-activation. However, most of these inhibitory effects of pinoresinol have been mediated by extracellular-signal-regulated kinase (ERK) 1/2 mitogen-activated

protein kinase (MAPK) phosphorylation and the NF-kappa B dependent. The results suggest that pinoresinol attenuates inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in brain disorders. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, Oxymatrine ipilimumab – which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response – administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma.


A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3: 1: 1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction).

Whereas the diagnosis is relatively easy to establish in the typi

Whereas the diagnosis is relatively easy to establish in the typical form and if the patient is seen early, the emergence of possible additional cognitive or psycho-behavioural disorders can lead to a misdiagnosis in favour of a frontotemporal selleck chemical dementia syndrome or even probable Alzheimer’s disease. (C) 2013 Elsevier Masson SAS. All rights reserved.”
“The last decade marked a turning point in the knowledge of frontotemporal lobar degenerations (FTLD). Major discoveries were made with the identification of TDP-43 and FUS, two novel key players in FTLD. The growing number of FTLD genes has considerably changed our clinical practice.

The high intrafamilial variability of phenotypes underlines the necessity of a careful interview GSK1120212 in vivo concerning the family history, regarding FTLD diseases, but also other neurodegenerative and extra-neurological disorders. Knowledge of the different genetic forms of FTLD and their associated phenotypes become essential to propose appropriate genetic diagnosis to the patients, and deliver accurate genetic counseling to their families. We propose an algorithm based on four criteria to help to pinpoint the genetic cause of FTLD: Presence of ALS in the patient or family; age at onset of FTLD; progranulin plasma level; and other

disorders present in the patient or family. Presence of ALS is strongly indicative of a C9ORF72 expansion; a very early age at onset (<50 years), parkinsonism and oculomotor dysfunction are indicative of MAPT mutations; whereas hallucinations, CBDS and PNFA are indicative of PGRN mutations. Selonsertib A C9ORF72 repeat expansion should be searched for therefore in patients with FTLD-ALS, followed by sequencing of exon 6 of TARDBP gene in negative cases. Since C9ORF72 expansions are as frequent as PGRN mutations in

patients with pure FTLD, both should be investigated, except in early familial FTLD (<50) where MAPT mutations should be searched for first. VCP, SQSTM1 and hnRNPA2B1 gene-sequencing could be proposed in patients or families presenting ‘multisystem proteinopathy’. The genes currently identified explain 50-60% of familial forms of FTLD. The identification of new FTLD genes involved remains a major challenge to gain further insight into the pathology and even better clarify the classification of FTLD in the future. (C) 2013 Published by Elsevier Masson SAS.”
“Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. Studies of other neurodegenerative diseases have shown imaging and biomarker evidence of disease onset many years prior to the development of symptoms.

CONCLUSION: If intraoperative electrical stimulation produces con

CONCLUSION: If intraoperative electrical stimulation produces contraction of the upper trapezius muscle, no repair is needed. In proximal injuries, the platysma motor Nec-1s nmr branch should be transferred to the accessory nerve; whereas

in paralysis distal to the sternocleidomastoid muscle, the accessory nerve should be explored and grafted.”
“Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide

at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable click here period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR-binding fiber protein eFT-508 even while CAR protein and mRNA levels

remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection.”
“BACKGROUND: Middle cerebral artery (MCA) aneurysms are often considered unsuitable for endovascular coiling because of unfavorable morphological features. With improvements in endovascular techniques, several series have detailed the results and complications of endovascular treatment of MCA aneurysms.

OBJECTIVE: We performed a systematic review of published series on endovascular treatment of MCA aneurysms including our experience.

METHODS: We conducted a computerized MEDLINE search of the literature on endovascular treatment of MCA aneurysms. Only studies examining a consecutive case series of MCA aneurysms were included. We then extracted information regarding intraprocedural complications, procedural mortality and morbidity, immediate and long-term angiographic outcomes, and re-treatment rate. Analysis was done including 40 MCA aneurysms treated at our institution.


Conclusions: The kidney sparing



Conclusions: The kidney sparing

approach rate in a community based health care system can approach rates at major academic centers. This practice pattern appears related to the addition of recent graduates and urological oncologists but also to a change in long-standing practice patterns of other community urologists. These data suggest that the use of kidney sparing approaches nationwide and the associated renal functional benefits may continue to increase.”
“T buy PLX4032 helper (Th) cell subsets secrete cytokines that regulate other immune cells. Interleukin (IL)-17 and IL-22 belong to a new class of cytokines with predominant effects on epithelial cells. Thus, these cytokines are key molecules in several disease processes. IL-17 and IL-22 are released by leukocytes find more such as Th and natural killer cell populations. Both IL-17 and IL-22 induce an innate immune response in epithelial cells, but their functional spectra are generally distinct. IL-17 induces

an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is protective/regenerative. This review juxtaposes IL-17 and IL-22 and describes overlaps and differences regarding their cellular sources, biochemical structure, signaling cascades in target cells, and function.”
“It is well established that under fasting conditions the expression of the orexigenic neuropeptide agouti-related peptide (AGRP) is up-regulated in the hypothalamic arcuate nucleus (ARC), while inconsistent data exist regarding fasting regulation of the anorexigenic neurohormone proopiomelanocortin (POMC). Inconsistencies might have methodological reasons, especially concerning neuromorphological and/or experimental (nutritional) specificity. We analyzed the expression of both neuropeptides in ARC neurons, using lasercapture microdissection (LMD) and real-time PCR in 12 h fasted vs. fed Wistar rats as well as after a standardized glucose load. i.e.. under clinically PKC412 cell line relevant conditions in terms of diagnosing glucose intolerance in the human. Under fasting conditions,

clear up-regulation of AGRP was observed, with increasing magnitude in ARC single neurons (SNP) as compared to ARC cell layers (+125% vs. +23%, resp.), closely correlated to hypoinsulinemia and hypoleptinemia. Surprisingly, in the fasting state POMC was not found to be down-regulated, neither in ARC cell layers nor in ARC single neurons (+9% vs. +6%). However, glucose-refeeding under diagnostically relevant conditions led to strong neuronal up-regulation of POMC expression in ARC SNP (+128%), and AGRP down-regulation (-50%). In conclusion, experimentally, topographically, and analytically specific and standardized conditions confirmed AGRP in ARC neurons as being neuronally up- and down-regulated, resp., depending on the general nutritional state, while POMC was found to be (up-) regulated only after peripheral glucose load.

008) and omega 3 fatty acids concentrations (p=0 031) Our result

008) and omega 3 fatty acids concentrations (p=0.031). Our results suggest that altered placental LCPUFA may result in altered membrane lipid fatty acid composition leading to increased release of sFlt-1 in circulation. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objectives: We have previously demonstrated that biventricular pacing increased cardiac output within 1 hour of weaning from cardiopulmonary bypass in selected patients. To assess the possible sustained benefit, we reviewed in the present study the effects of biventricular pacing on the mean arterial pressure after chest closure.

Methods: A total of 30 patients (mean Ispinesib datasheet ejection

fraction 35% +/- 15%, mean QRS 119 +/- 24 ms) underwent coronary bypass and/or valve surgery. The mean arterial pressure was maximized during biventricular pacing using atrioventricular delays of 90 to 270 ms and interventricular delays of +80 to -80 ms during 20-second intervals in random sequence. Optimized biventricular pacing was finally compared

with atrial pacing at a matched heart rate and to a sinus rhythm during 30-second intervals. Vasoactive medication and fluid infusion rates were held constant. The arterial pressure was digitized, recorded, and integrated. Statistical significance was assessed using linear mixed effects models and Bonferroni’s correction.

Results: Optimized atrioventricular delay, ranging from 90 to 270 ms, increased the mean arterial pressure 4% versus nominal and very selleck chemical 7% versus the worst (P<.001). Optimized interventricular delay increased pressure 3% versus nominal and 7% versus the worst. Optimized biventricular pacing increased the mean arterial pressure 4% versus sinus rhythm (78.5 +/- 2.4 vs 75.1 +/- 2.4 mm Hg; P=.002) and 3% versus atrial pacing (76.4 +/- 2.7 mm Hg; P=.017).

Conclusions: Temporary biventricular pacing improves the hemodynamics

after chest closure, with effects similar to those within 1 hour of bypass. Individualized optimization of atrioventricular delay is warranted, because the optimal delay was longer in 80% of our patients than the current recommendations for temporary postoperative pacing. (J Thorac Cardiovasc Surg 2012;144:1445-52)”
“Aim: Integrin alpha(v)beta(3) plays a significant role in angiogenesis during tumor growth and metastasis, and is a receptor for the extracellular matrix proteins with the exposed arginine(R)-glycine(G)-aspartic acid(D) tripeptide sequence. The over-expression of integrin alpha(v)beta(3) during tumor growth and metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid tumors. Considering the advantages of Lu-177 for targeted radiotherapy and enhanced tumor targeting capability of cyclic RGD peptide dimer, an attempt has been made to optimize the protocol for the preparation of clinical dose of Lu-177 labeled DOTA-E[c(RGDfK)](2) (E = Glutamic acid, f = phenyl alanine, K = lysine) as a potential agent for targeted tumor therapy.

In this review we discuss studies that have clarified nuclear siz

In this review we discuss studies that have clarified nuclear size control mechanisms and how these results have or will contribute to our understanding of the functional significance of nuclear size.”
“This study evaluated four fluorescent-protein conjugates to monitor microcirculatory variables MX69 price using the murine cremaster muscle and determined acute and long-term responses to repeated administration of FITC-BSA [conjugated at the University of Sheffield (UoS)] within a dorsal microcirculatory chamber (DMC) in rats. For analysis of the cremaster muscle, male C3H/HeN mice were anaesthetized, the cremaster muscle was exteriorized,

then TRITC-BSA, TRITC-dextran, FITC-BSA, FITC-BSA (UoS) or FITC-dextran (0.25 ml/100 g) were administered systemically. The microcirculation was viewed with epi-illumination every 10 min for 120 min. For analysis

of the DMC, male Wis tar rats were implanted with the chamber. Three weeks later, FITC-BSA (UoS) was administered systemically, and the microcirculation response was monitored using three different protocols. In addition, in vitro stability of fluorescent conjugates was measured over 8 h. With regard to the cremaster muscle, initially no differences in interstitial fluorescence or vessel diameter were observed between the four fluorescent conjugates. By the end of the study, interstitial fluorescence from TRITC-dextran, FITC-dextran and FITC-BSA (Sigma) was significantly (p < 0.05) increased compared to FITC-BSA (UoS). With regard to 5-Fluoracil in vitro the DMC, there was no interstitial fluorescence leakage after 180 min or 5 weeks despite repeated administration, but a significant (p < 0.05) leak was detected between 4 and 24 h. FITC-BSA (UoS) was the most stable fluorescent conjugate both in vitro and in vivo and was comparable with other conjugates for evaluating skeletal muscle microcirculation using fluorescent in vivo microscopy. Copyright (C) 2012 S. Karger AG, Basel”
“delta-subunit containing extrasynaptic GABA(A) receptors are

potential targets for modifying neuronal activity in a range of brain disorders. With the aim of gaining more insight in synaptic and extrasynaptic inhibition, we used a new positive modulator, AA29504, of ISRIB mw delta-subunit containing GABA(A) receptors in mouse neurons in vitro and in vivo. Whole-cell patch-clamp recordings were carried out in the dentate gyrus in mouse brain slices. In granule cells, AA29504 (1 mu M) caused a 4.2-fold potentiation of a tonic current induced by THIP (1 mu M), while interneurons showed a potentiation of 2.6-fold. Moreover, AA29504 (1 mu M) increased the amplitude and prolonged the decay of miniature inhibitory postsynaptic currents (mIPSCs) in granule cells, and this effect was abolished by Zn2+ (15 mu M). AA29504 (1 mu M) also induced a small tonic current (12.7 +/- 3.2 pA) per se, and when evaluated in a nominally GABA-free environment using Ca2+ imaging in cultured neurons, AA29504 showed GABA(A) receptor agonism in the absence of agonist.


A Selleck CBL0137 significant correlation was found in SP NIS patients

with lesional load (R = 0.43, P < 0.01) but not with parenchymal fractions as measures of brain atrophy. A slight increase in serum FGF-2 levels was also found in R-R MS patients during relapse with gadolinium enhancing lesions and in SP patients with disability progression. These findings support the implication of FGF-2 in the pathogenesis of NIS and concur with recent reports of the involvement of FGF receptor signalling in the disruption of myelin production in differentiated oligodendrocytes and in the loss of adult oligodendrocytes and myelin in vivo due to FGF-2. (c) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Reward-based associative learning is mediated by a distributed network of brain regions that are dependent on the dopaminergic system. Age-related changes in key regions of this system, the striatum and the prefrontal cortex, may adversely affect the ability to use reward information for the guidance of behavior. The present study investigated the effects of healthy aging on different components of reward learning, such as acquisition, reversal, effects of reward magnitude, and transfer find more of learning. A group of 30 young ( mean age = 24.2 yr) and a group of 30 older

subjects ( mean age = 64.1 yr) completed two probabilistic reward-based stimulus association learning tasks. Older subjects showed poorer overall acquisition and impaired reversal learning, as well as deficits in transfer learning. When only those subjects who showed evidence of significant learning were considered, younger subjects showed equivalently fast learning irrespective of reward magnitude, while learning curves in older subjects were steeper for second high compared to low

reward magnitudes. Acquired equivalence learning, which requires generalization across stimuli and transfer of learned contingencies to new stimuli, was mildly impaired in older subjects.”
“Disturbance of circadian gene regulation might contribute to behavioral and psychological symptoms in dementia patients. This study was to evaluate the CpG island methylation status on the circadian gene promoters in dementia patients. We conducted a set of methylation specific polymerase chain reaction (mPCR) followed by nucleotide sequencing to analyze the methylation status within the promoters of nine circadian-related genes, including PERI, PER2, PER3, CRY1, CRY2, CLOCK, BMAL1, TIM and CK1 epsilon, in the genomic DNA from the peripheral blood leukocytes of 80 dementia patients and 80 age- and gender-matched controls. A total of seven dementia patients (7/80) had CpG island methylation in the circadian genes and none of the controls had methylation. There were three and four patients had CpG island methylation on the promoters of PERI and CRY1, respectively.

This is the first psychopharmacologic study to compare different

This is the first psychopharmacologic study to compare different doses of oxytocin in the same subject, thus the significance of the opposing responses is unclear.”
“Objectives To establish whether long-term use of melatonin PD0332991 mouse influences pubertal development, sleep quality and mental health development in children as compared with the normal Dutch population of the same age.


This follow-up research study was conducted in children included in a previous melatonin dose-finding trial. Outcomes were measured using questionnaires (Strength and Difficulties Questionnaire (SDQ), Children’s Sleep Habits Questionnaire (CSHQ) and Tanner Stages) adopted for Dutch children. Mean duration of therapy, persistence of effect, adverse events and (other) reasons leading to cessation of therapy were additional objectives of this study.

Results Mean years of usage (n=51) was 3.1 years (min 1.0 year, max 4.6 years), mean dose 2.69 mg (min 0.3 mg, max 10 mg). Mean SDQ score, mean CSHQ score and Tanner Stages standard deviation scores did not differ in a statistically significant way from published scores of the general

Dutch population of the same age and sex.

Conclusions This follow-up study demonstrates that melatonin treatment in children can be sustained over a long period of time without substantial deviation of the development of children with respect to sleep quality, puberty development 4SC-202 concentration and mental health scores, as compared with the general Dutch population.”
“Rationale Cue-exposure therapy (CET) has been advocated as a potentially effective treatment of addictive behaviours. Strategies that enhance learning may improve the outcome of CET. D-cycloserine (DCS), a Pritelivir manufacturer partial N-methyl-D-aspartate receptor agonist, has been shown to facilitate extinction of learned fear in rats and augment exposure-based treatment in some anxiety

disorders in man.

Objective This double-blind placebo-controlled pilot study used a cue-exposure paradigm, salient for an individual’s alcohol drinking, to see if DCS would reduce cue-reactivity compared with placebo.

Methods Sixteen abstinent, alcohol-dependent individuals were randomised to receive either a single-dose (250 mg) DCS or placebo before CET sessions, separated by at least 1 week. Subjective responses were assessed using the Alcohol Urge Questionnaire (AUQ) and visual analogue scales. Cardiovascular responses were assessed using Finapres(C).

Results The cue-exposure paradigm significantly increased craving assessed with the AUQ during the first session. In subsequent sessions, the degree of craving was reduced. However, no significant difference was seen between the DCS and placebo groups in any outcome measure. The variability of responses between individuals was great with more than half the groups reporting no or very small changes in AUQ scores.

Conclusion This is the first human study to our knowledge to assess the efficacy of DCS in facilitating CET in alcohol dependence.