Allodynic behavior was present 4 days after injury and for up to 5 weeks later (experiment duration). The intracisternal and intraperitoneal administration of bromocriptine (D2R-agonist) decreased allodynic behavior in the lesioned

animals. Furthermore, the injection of bromocriptine intracisternally, after that of systemic sulpiride, had no effect on the allodynia observed, revealing the clear implication Inhibitors,research,lifescience,medical of D2R receptors locally in allodynic behavior. Hence, the antiallodynic effect of bromocriptine was inhibited by D2-type receptor antagonist sulpiride. This result clearly demonstrated the implication of dopamine in trigeminal pain. To support the implication of a segmental mechanism in the neuropathic pain symptom Inhibitors,research,lifescience,medical observed in DA depleted animals, the expressions of PKCγ, which reveal central sensitization (Malmberg et al. 1997), and those of pERK1/2, which constitute a molecular hallmark of pain sensation (Ji et al. 1999), were explored in the MDH. In this study, we highlight significant upregulation in the expression of both PKCγ and pERK1/2 in the MDH of 6-OHDA-lesioned rats when compared to shams. Moreover, the number of pERK1/2-positive cells

was significantly higher in the ipsilateral MDH of the stimulated orofacial region when compared to the contralateral nonstimulated region. pERK1/2 was also expressed by cells of lamina I which normally Inhibitors,research,lifescience,medical convey Tofacitinib baldness nociceptive stimuli. Moreover, these markers were present in distinct cell subtypes. The segmental implication of D2R is also highlighted by the administration of bromocriptine which decreased the Inhibitors,research,lifescience,medical number of pERK1/2 cells and the expression of PKCγ within the Inhibitors,research,lifescience,medical MDH. The present data provided clear evidence of the implication of the dopaminergic nigrostriatal circuitry in the DMA observed in DA-depleted rats and demonstrated for the first time that nonnoxious stimulus can trigger noxious response in rats with a bilateral

nigrostriatal pathway lesion. However, we do not exclude the participation of the VTA (mesolimbic and mesocortical pathways; Magnusson and Fisher 2000; Wood 2006; Sogabe et al. 2013) in the DMA as our lesion targeted also this structure. Dopamine Brefeldin_A and nociception Rats with a bilateral dopaminergic nigrostriatal lesion demonstrated a significant decrease in TH labeling in the VTA, the striatum, and the SNc. Also noted was a significant decrease in the number of TH-positive cells within the SNc, as reported previously (Paillé et al. 2007; Ouachikh et al. 2013; Zengin-Toktas et al. 2013). The bilateral dopamine-depleted animals presented a severe body movement alteration (rotarod) when compared to the controls. These rats were able to move (Paillé et al. 2007; Ouachikh et al. 2013; Zengin-Toktas et al. 2013) and perform all the movements required for the Vos test.

45 Expression of an IGF-1R dominant negative mutant in Ewing’s sarcoma cells

markedly decreased proliferation and induced apoptosis. When cells expressing a dominant negative IGF-1R were injected into nude mice, the tumor formation and metastatic abilities of the Ewing’s sarcoma cells were reduced, and survival of the mice increased.46 In addition, other variations of dominant negative mutations of the IGF-1R in mice blocked the growth Inhibitors,research,lifescience,medical of the lung this research cancer cell line.47 IGF-1R over-expressed in a variety of primary cancers increased tumor growth and also increased nodal metastases.48 Altogether, these studies suggest that IGF-1 signaling through the IGF-1R plays critical roles in tumor growth, metastasis, and inhibition of pro-apoptotic factors. INSULIN

RECEPTOR Similar to the IGF-1R involvement in tumor development, studies involving the insulin receptors indicated a connection between insulin receptors and cancer. Higher levels of IR expression were found in human breast Inhibitors,research,lifescience,medical cancer than in normal breast tissue.49 Other studies find more demonstrated that the IR is over-expressed in malignancies such as cancer of Inhibitors,research,lifescience,medical the thyroid, colon, lung, ovary, and sarcomas.50–52 Analysis of five types of human adenocarcinoma (breast, colon, pancreas, lung, and kidney) yielded evidence of higher levels of IR on the endothelium cells. This evidence connects IR over-expression to angiogenesis.53 Inhibitors,research,lifescience,medical Moreover, in-vitro angiogenesis assays that tested various commercially available insulin compounds demonstrated that insulin has the potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC).53 Similar results were obtained from down-regulation

of IR using shRNA. Thus IR inhibition in cancer cell lines (LCC6 and T47D) causes reduced Akt activation by insulin, with no involvement of the IGF-1R. When the cells were transplanted into mice, reduced growth, angiogenesis, and lymphangiogenesis were detected, and Inhibitors,research,lifescience,medical reduced expression of hypoxia-inducible factor-1-α(HIF1-α), and vascular endothelia growth factor-A (VEGF-A), and VEGF-D were measured.54 Met-1 breast cancer cells that over-express the viral oncogene PyVmT Anacetrapib (polyoma virus middle T antigen) show interaction of IGF-1R and IR with the PyVmT that increased with IGF-1 and insulin presence. The interactions enhanced tyrosine phosphorylation of PyVmT and raised recruitment of Src and PLCγ1 to PyVmT. Src and PLCγ1 play a role in tumorigenesis. In this setting Met-1 cells demonstrated increased proliferation, survival, migration, and invasion. Also, Met-1 cells with dysfunction of IR and IGF-1R that were transplanted into the hyperinsulinemic MKR (unique transgenic model of T2D) mice lost the ability to initiate tumor growth.

Introduction The antipsychotic drugs are a widely used pharmacotherapy, estimated in year 2000 as prescribed to 1.2% of the adult non-institutionalized European population [Alonso et al. 2004], a figure that is very likely to have increased in the past decade. While the largest proportion #selleck chemicals randurls[1|1|,|CHEM1|]# of these prescriptions is likely to have been for schizophrenia and related disorders, some may be used in treating, often with little in the way Inhibitors,research,lifescience,medical of an evidence base, a variety of behavioural problems in childhood and in the elderly. Antipsychotics have also been made available in the past

decade to people with bipolar disorder, and are now a first-line treatment for mania. The most recent meta-analysis concluded that antipsychotic medication is, overall, significantly more effective than mood stabilizers in the treatment of acute mania [Cipriani et al. 2011]. This important study, employing a multiple-treatments Inhibitors,research,lifescience,medical meta-analysis, showed haloperidol to be significantly more effective than most other drugs including

lithium and the atypical Inhibitors,research,lifescience,medical antipsychotics, other than risperidone and olanzapine. Furthermore, all antipsychotics had higher acceptability than lithium and several other mood stabilizers. The aim of this article is to review the clinical pharmacology of the antipsychotic drugs, relating receptor actions to their therapeutic and adverse effects. While the major emphasis will be on the consequences Inhibitors,research,lifescience,medical of the use of the newer atypical antipsychotics in the treatment of bipolar disorder, there will be a particular focus on the most recently available of these, asenapine. As a pharmacological review, this article does not make recommendations regarding the value of prescribing particular drugs in any clinical situation, for which the reader is referred to evidence-based guidelines such as those published by the Inhibitors,research,lifescience,medical BAP [Goodwin

and Consensus Group of the British Association for Psychopharmacology, 2009]. Comparative receptor pharmacology of asenapine Asenapine is the latest addition to Brefeldin_A the antipsychotic drugs available for the treatment of mania in bipolar disorder in Europe and which include aripiprazole, olanzapine, quetiapine, risperidone and, in some countries, ziprasidone. Hereinafter this group of drugs will be referred to as the atypicals, although there are other drugs not specifically licensed for the treatment of bipolar disorder, notably clozapine and selleck chemicals Olaparib amisulpride, which are considered atypical antipsychotics. Clozapine, licensed solely for treatment-resistant schizophrenia, will occasionally be referred to in this review as it is sometimes considered the archetypal atypical and has some pharmacology in common with asenapine. Originally developed by Organon (as Org5222), asenapine is described as a tetracyclic antipsychotic, reflecting its core molecular structure.

Second, although not all trials have been positive, there is compelling evidence that psychotherapies can be beneficial in augmenting standard pharmacotherapy in bipolar disorder in terms of symptom reduction, episode prophylaxis, and improvement of adherence and psychosocial functioning. Third, there is some evidence, rather surprisingly, that these interventions are better at delaying the onset, of mania than in addressing the active symptoms of depression (the STEP-BD study targeting bipolar depression is a notable Inhibitors,research,lifescience,medical exception). The next, evolution of clinical research on psychotherapy for bipolar

disorder would need to address: (i) which intervention works best for which patients; (ii) how these interventions Inhibitors,research,lifescience,medical can be made available outside of academic medical centers; and (iii) what the essential ingredients of

psychotherapy for bipolar disorder are. Bipolar disorder is an enormously heterogeneous condition, and it is highly selleck chemicals JQ1 likely that therapies would need to target subgroups of people with bipolar Inhibitors,research,lifescience,medical disorder to be adequately personalized. Presently, there are few evidence-based moderators or mediators of treatment selleckchem Nutlin-3a effectiveness in bipolar disorder. In their negative trial of CBT for bipolar disorder, Scott et al20 found that individuals with fewer previous episodes appeared to derive benefit from treatment, whereas those who had more episodes did not. Although these kinds of mediators require replication over multiple Inhibitors,research,lifescience,medical studies, it. will be important to understand who will and who might not benefit, from augmentation with psychotherapy. In addition

to clinical variables that might moderate outcome, whether and how interventions are accepted and experienced in different ethnic groups deserves study. In psychosocial interventions for other conditions, major efforts have been undertaken to adapt psychosocial treatments to culture-based preferences Inhibitors,research,lifescience,medical and values. There are also efforts under way to modify the above intervention modalities to address subgroups Entinostat of people with bipolar disorder, such as those with chronic physical illnesses.32 In addition, understanding how these interventions can be successfully transported to community settings is a needed next step. While approximately half of the STEPBD sample had attended counseling or psychotherapy in the community prior to their enrolment,33 it is doubtful that many have access to the evidence -based psychotlierapies described above. It is also unlikely, due to financing and staffing limitations, that 20-session packages, as implemented in the research studies cited above, will be feasible in many settings.

556). Table 2. Variation in CTO use by London borough and ethnicity. selleck bio Statutory reasons and conditions Statutory reasons for CTO initiation and kinase inhibitor 17-DMAG commonly stated conditions of CTOs are detailed in Table 3. Rarer conditions included a requirement to meet with a housing officer, eat lunch twice a week at an eating disorders clinic, attend drug counselling/rehabilitation/occupational therapy, and taking medication in front of staff. Medication At time of CTO initiation, 193 patients (99%) were prescribed an antipsychotic, and first-generation (typical) antipsychotic LAIs were most commonly used (see Table 3). Regarding antipsychotic doses, the

mean %BNF was 61.6% (SD 37.1, range 2.5–183.3%). Of the total sample 7.2% Inhibitors,research,lifescience,medical had antipsychotic (combined) doses exceeding 100% BNF limits and 9.7% were prescribed two antipsychotics.

The most commonly prescribed Inhibitors,research,lifescience,medical LAIs were risperidone LAI, pipothiazine palmitate and flupenthixol decanoate. Of those with a diagnosis of schizophrenia, 88/138 (63.8%) were prescribed an LAI. SOAD involvement Only 136 (69.7%) patients received SOAD certification within 6 months (see Table 3). Completion rates of SOAD certification within the required time-frame (usually 1 month) did not improve over the study duration: Q1, 16/64 (25.0%); Q2, 9/62 (14.5%); Q3, 3/39 (7.7%); Q4, 1/30 (3.3%); total, 29/195 (14.9%). The mean time from CTO onset to SOAD certification was 66.6 days (SD 40.8, range 1–175 days, N = 136); Inhibitors,research,lifescience,medical for those with a standard 1 month time requirement the mean was 67.4 days

(SD 41.4, range 1–175 Inhibitors,research,lifescience,medical days, N = 120). Discussion Strengths, weaknesses and principal findings This is the largest reported study on CTOs in England and Wales to date and comprised all 195 patients commenced on a CTO within the first year of legislation in a large mental health trust. A key strength of this study is that it used a systematic sampling strategy which included all patients, thus avoiding sampling bias. Weaknesses of this study include lack of detail regarding education, length of contact with psychiatric services, number of prior psychiatric hospital admissions (compulsory Inhibitors,research,lifescience,medical or voluntary) and duration of index admission (leading to CTO) and lack of a matched comparison group. We did not aim to definitively address the question of whether or not CTOs are beneficial or efficacious, which requires an RCT [Burns and Dawson, 2009; Churchill et al. 2007]; rather, we aimed to investigate how CTOs Drug_discovery are being used with particular regard to medication use. Key findings included the considerable variability in CTO use across the four boroughs which the Trust serves. Over half of the patients were of black ethnic origin which is more than twice that suggested by the population census data for the four boroughs (13.3–25.9%) [Office for National Statistics, 2001]. Further, common CTO conditions included clinical assessment, medication adherence, specified place of residence and access to residence.

159-161 Interestingly, it has been shown that miRNAs are endogenously expressed in plasma and their expression profile is similar in blood cells.162 More interestingly, under healthy conditions, these miRNAs are stably expressed in blood cells; however, under pathological conditions, the profile of miRNAs changes significantly, suggesting the possibility that peripheral miRNAs can be used as a reliable biomarker under http://www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html disease conditions. Although the source Inhibitors,research,lifescience,medical of miRNAs in peripheral cells is not clear, it has been shown that miRNAs can be released actively or passively from tissues

into the circulating blood.162,163 The actively secreted miRNAs are enclosed in exosomes164 and protected by RNA binding proteins including NPM1,165 HDL,166 or Argonaute2.167 Therefore, measuring miRNAs in blood cells is highly reproducible. Interestingly, it has been shown that exosomes containing miRNAs are excreted physiologically in response to stress or brain injury, suggesting Inhibitors,research,lifescience,medical that these miRNAs can be ideal biomarker candidates.168-170 Exosomal miRNAs are processed by the same

machinery used in miRNA biogenesis and thus have widespread consequences within the cell by inhibiting the expression of Inhibitors,research,lifescience,medical target protein-coding genes.169 Over the past several years, attempts have been put forward towards developing circulating miRNAs as a potential biomarker for many diseases. These include Inhibitors,research,lifescience,medical cancer and cardiovascular, inflammatory, and neurodegenerative diseases.128,171-173 In cancer patients, miRNAs have not only been shown to be www.selleckchem.com/products/mek162.html useful indicators of various types of cancer, but based on miRNA profiling, it can be shown which patient group responds better to a particular treatment regimen.125 In neurological disorders, there is a significant correlation between circulating miRNAs and brain disease and injury.174 For example, miR-9 is decreased in blood cells, and in the cortex and hippocampus Inhibitors,research,lifescience,medical of Alzheimer’s disease patients.175 Similarly, circulating

miR-34 serves as a novel biomarker for Huntington’s disease.176 Identifying biomarkers in these diseases has been a challenging Drug_discovery task due to the heterogeneity and complex nature of psychiatric illnesses. Nonetheless, emerging studies provide evidence that miRNAs can be used successfully as biomarkers in these illnesses. For example, in schizophrenia patients, several circulating miRNAs (miR-181b, miR-219-2-3p, miR-1308, let-7g, and miR-195) have been identified as potential disease biomarkers.177 Plasma miR-134 levels in drug-free, 2-week medicated, and 4-week medicated bipolar mania patients were significantly decreased when compared with controls, and its level increased following medication.

66 This position tracking technique has since been interleaved within real-time imaging sequences to automatically move the image plane position to the selleck catalog catheter tip location during device manipulation.61,67 While a single tracking coil is sufficient to simply shift the image position, multiple tracking points are needed to maximize visualization of the device body or to orient imaging relative to the catheter tip direction. Multicoil designs and tracking algorithms have been developed to reduce the need for separate Inhibitors,research,lifescience,medical matching

circuits in space-constrained catheter lumens.68,69 Other magnetic field and electric field-based position finding techniques have been developed for medical device tracking that could also be used for catheter tracking in the MRI scanner.70–72 Some of these systems generate Inhibitors,research,lifescience,medical both position and orientation information for each sensor assembly.72,73 These systems may provide more accurate and catheter space-efficient options for device tracking. They can also reduce the performance penalty and avoid the scanner-specific complexities associated with interleaving tracking and real-time imaging sequences. Inhibitors,research,lifescience,medical An alternative technique for device visualization uses non-slice-selective imaging to produce an effect similar to projection

X-ray fluoroscopy.74,75 The non-slice-selective catheter imaging plane can be intersected with slice-selective images containing the target anatomy to assist guidance of the catheter tip. This technique

may be used to provide a “fluoroscopy” view of devices Inhibitors,research,lifescience,medical using a number of catheter antenna designs 69,76–78 (Figure 3A). Another factor that affects device navigation in the MRI environment is the physical constraint of performing procedures near and within the narrow MRI bore. The availability of shorter, wider-bore, high-field MRI scanners is making this less of an issue. Remote catheter steering is also gaining interest in the EP field to facilitate point-by-point electrical mapping of the selleck chemicals Nintedanib cardiac chambers and assist stable device placement during ablation.79,80 Inhibitors,research,lifescience,medical Some of these techniques may be amenable to use in the MRI environment. A robotic catheter manipulation system that uses steerable sheaths with multiple pull wires was recently used to perform atrial fibrillation ablation in patients.81 A magnetic remote steering technique AV-951 has also been described that utilizes the torque generated by current-carrying coils in the static MRI magnetic field to deflect a catheter tip.82,83 3-D ANATOMY AND INTRACARDIAC ELECTROGRAM VISUALIZATION The ability to generate real-time images with arbitrary orientations in addition to anatomically detailed 3-D images with flexible tissue contrast makes CMR well suited for navigating complex arrhythmia anatomy and delineating complex ablation patterns. This flexibility also introduces the potential for disorientation and information overload.

Mandard tumour regression grade, originally described for oesophageal cancer, is the most commonly used (51). It consists of five different grades based on ratio of fibrosis to tumours. We identified, for the first time, a group of genes that can be used as markers to quantify tumour response following neoadjuvant therapy in rectal cancer patients. Conclusions The list of the genes identified in this study could serve as molecular Inhibitors,research,lifescience,medical markers to complement existing histopathological factors in screening, diagnosis, follow up and therapeutic strategies for individualised care of patients (Figures 7,​,88). Figure 7 Potential biomarker for CRC. Genes identified in the study as potential biomarket

for CRC screening, diagnosis and disease progression Figure 8 Correlation gene expression and CRC management stratigies Acknowledgements

We would like to thank Inhibitors,research,lifescience,medical the National Breast Cancer Research Institute (NBCRI) for their financial support of the study. Disclosure: The authors declare no conflict of interest.
Surgical resection is the only curative option for liver metastases from colorectal cancer (CRLM); however, the incidence of unresectable CRLM remains high (1). Recently, systemic chemotherapy for unresectable metastatic colorectal cancer has remarkably progressed. In a retrospective analysis, more than 12% of cases of initially unresectable CRLM converted Inhibitors,research,lifescience,medical to resectable status after the patients showed responses to chemotherapy and were reported to show a good 5-year survival rate of more than 30% (2). Surgical procedures such as two-staged hepatectomy have also been developed for such cases (3,4). On the other hand, neoadjuvant chemotherapy followed by hepatic resection for initially resectable CRLM Inhibitors,research,lifescience,medical has also been suggested to be effective (5). Histopathological tumor regression due to preoperative

chemotherapy has recently been recognized Inhibitors,research,lifescience,medical to be an important indicator of a significantly better prognosis in patients with CRLM (6). In addition, a pathological CYC202 complete response to preoperative chemotherapy was associated with a 5-year survival of 75% in patients with CRLM compared to 33% in patients with a minor pathological response (7). However, Adam et al. (8) showed that the incidence of pathological complete responses (pCRs) is insufficient, at approximately 4%, and 71% of the CRLM measured less than 3.0 cm in diameter in cases of pCR. Smaller liver deposits may be associated with Anacetrapib a higher incidence of pCR due to preoperative chemotherapy. We herein report the case of a patient with synchronous solitary liver metastasis from sigmoid colon cancer. The maximum diameter of the liver deposit was 5.7 cm and its grade was therefore H2 selleckchem Brefeldin A according to the Japanese classification (9). A pCR was detected after the patient underwent deferred hepatic resection after neoadjuvant chemotherapy consisting of capecitabine, oxaliplatin and bevacizumab (XELOX + Bev).

This was recently selleck catalog noticed in the CORRECT trial, comparing regorafinib – an oral multikinase inhibitor of angiogenic, oncogenic, and stromal kinases – to best supportive care in mCRC patients, who had progressed after all approved standard therapies (7). Noteworthy response rate was only 1%, but despite lack of tumor regression, Inhibitors,research,lifescience,medical disease-control was seen in almost half of patients, and this translated into a significantly prolongation of median PFS

(1.7 to 1.9 months; HR 0.49) and OS (5.0 to 6.4 months; HR 0.77). In the Franck et al. study, PFS was 2.1 Axitinib VEGFR inhibitor months and OS 6.8 months, which are almost identical to the CORRECT study. It can therefore not be excluded that treatment with Inhibitors,research,lifescience,medical lapatinib may cause stabilisation of disease with prolongation of life without objective response according to RECIST in a selected group of patients. There has been great progress in understanding of and treatment of mCRC in recent years. However our knowledge on the mechanisms contributing to disease progression and resistance to therapy are still sparse, and decisions on treatment strategy in later lines are most often based on the profile in the primary tumor. In breast cancer it has been demonstrated that there might be discordance in the molecular Inhibitors,research,lifescience,medical profile of the primary and metastases with potential implications

for therapy (8). It is therefore very important that clinical studies – also in late lines of therapy – are combined with translational studies including re-biopsy of metastases resulting in new important knowledge which are the basis for further personalized Inhibitors,research,lifescience,medical treatment in patients with mCRC. Footnotes No potential conflict of interest.
In the year 2010, the incidence of newly diagnosed pancreatic cancer in USA was 43,140 and deaths attributable to pancreatic cancer were 18,770 (1). Among recently diagnosed pancreatic cancer patients, 65-70% will have advanced disease (stage

III-IV) at initial presentation. Advanced pancreatic cancer has a very poor prognosis, Inhibitors,research,lifescience,medical with a median survival of 2-6 months for stage IV disease and 6-11 months for stage III disease. AV-951 Overall, the 5-year survival among these patients is only 5-7% and the majority of patients survive less than 1-2 years. Even among patients who undergo surgery with curative-intent, >90% develops disease progression within 12-18 months. This poor prognosis is attributable to late stage presentation, lack of effective treatments, early recurrence and absence of clinically useful biomarker(s) which can detect pancreatic cancer in its precursor form(s) or earliest stages (2-4). A wide-variety of tumor markers derived from serum, pancreatic tissue, pancreatic juice, saliva and/or stool has been proposed for early diagnosis as well as to predict prognosis in pancreatic cancer patients.

71 Although not previously examined in TD studies, a SNP in RGS2 (rs4606) has been associated with extrapyramidal symptoms in two studies.74,75 Although a third study was negative, this regulator of intracellular dopamine signaling merits additional research.76 http://www.selleckchem.com/products/FTY720.html prolactin elevation While prolactin #protein inhibitors randurls[1|1|,|CHEM1|]# elevation has also not been

widely studied across most of the genes listed in Table I, there have been seven published studies examining DRD2 TaqlA.77-83 As displayed in Table II, these studies have yielded mixed results across Inhibitors,research,lifescience,medical a variety of APDs. Notably, the three positive studies all reported that the Al allele was associated with increased risk for hyperprolactinemia, and a fourth study demonstrated the same effect in females only. This is the opposite allele that Inhibitors,research,lifescience,medical was associated with TD, which may reflect the fact that prolactin response is mediated via the tuberoinfundibular pathway (hypothalamus and pituitary).84 Table II. List of studies of the Taq1A polymorphism (rs1800497) from the ANKK1/DRD2 locus in association with antipsychotic drug-related Inhibitors,research,lifescience,medical prolactin levels. Weight gain It has been suggested that increased 5-HT binding profiles may account for the increased liability to weight gain observed in the second-generation antipsychotics.85 A survey of the literature of the regulation of feeding behavior

points to a major role for 5-HT, with both animal and human investigations showing, in general, that increasing 5-HT results in decreased feeding, with the reverse also true.86

Pharmacologic agonists of 5-HT2C lead to decreased feeding in animals87 it is logical to speculate that 5-HT2C antagonists, including most secondgeneration antipsychotics, might Inhibitors,research,lifescience,medical lead to increased food intake. Perhaps Inhibitors,research,lifescience,medical the best evidence for a specific role of serotonin-related genetic factors in antipsychotic-induced weight gain is provided by studies of the promoter region polymorphism, -759 T/C (rs3813929), in the HTR2C gene (on the X chromosome). Reynolds and colleagues88 studied 123 adult drug-naïve Han Chinese SCZ patients treated primarily with risperidone or chlorpromazine. Subjects with the T allele at this locus gained significantly less weight than subjects with the C allele in short-term (6- and 10-week) treatment; none of the 27 subjects with the T allele met criteria for severe (>7%) weight gain after 6 weeks, as compared AV-951 with 28% of the 96 subjects without the T allele. Two studies89,90 also reported an association of the T allele to reduced weight gain in a small samples of clozapinetreated patients, although this effect was only significant in males in one of these. Ellingrod and colleagues91 reported that the T allele is associated with less weight gain in Caucasian patients treated with olanzapine, and Templeman et al92 reported the same for weight gain associated with a mixed group of antipsychotics in a small Spanish first-episode cohort.