The main advantage of cytometry over immunohistochemical analysis

The main advantage of cytometry over immunohistochemical analysis in the initial diagnosis is speed, and may be helpful when the material for immunohistochemical analysis is not available, such as in the case of fine-needle aspiration (9). ALCL is a T-cell lymphoma immunophenotypically characterized by positive CD30 staining in a membranous and Golgi zone pattern. Ganetespib supplier Approximately 60-85% ALCL cases are Inhibitors,research,lifescience,medical positive for ALK protein. The translocation

[2;5] between the ALK gene on chromosome 5 is the most common cytogenetic abnormality that leads to upregulation of ALK protein. The majority of ALC cases will show one or more

T-cell-associated antigens. However, there are cases of ALCL that are negative for all T-cell markers and they are known as null-cell type. The optimal treatment is not yet defined due to the low incidence of this disease. Surgery, radiotherapy and chemotherapy were all reported Inhibitors,research,lifescience,medical as treatment modalities alone or in combination Inhibitors,research,lifescience,medical (11). Only 17 patients, including our case, have been surgically treated. The importance of surgical resection for a cure or for a reduction of tumor burden cannot be assessed by this limited series. Whether or not systemic treatment with chemotherapy will give comparable results Inhibitors,research,lifescience,medical to surgery in resectable cases is also not currently known. Pescovitz et al. (10) noted that the disease-free survival rate for 5 patients

treated with resection and combined chemotherapy was 80%, compared with 54% survival for chemotherapy alone. But Page et al. (7) reported complete remission in 83.3% of 24 cases evaluated with combination chemotherapy. Five year cause specific and failure free survival rates were 87.1% and 70.1% respectively. Outcomes are poorer in patients with AIDS, and in those with coexisting liver disease. Currently, the most common Inhibitors,research,lifescience,medical treatment of PHL involves combination chemotherapy CHOP. Rituximab, an anti CD 20 monoclonal antibody, is added to this chemotherapy regimen if the histology confirms that the lymphoma PAK6 is CD 20 antigen positive. Massive liver infiltration, high index of proliferation, advanced age, elevated LDH levels, cirrhosis and increased levels of β2-microglobulin are the worst prognosis factors (12). This is, to our knowledge, the first reported case of primary hepatic anaplastic large cell Ki-1 non-hodgkin lymphoma in a setting of adult celiac disease. The only link between both diseases is a markedly increased incidence of gastrointestinal T-cell lymphoma in celiac disease.

The fungicidal/fungistatic natures of the extracts were determine

The fungicidal/fungistatic natures of the extracts were determined as described by Thompson.9 The inhibited fungal discs from the extract treated dishes were sub-cultured in a fresh medium, and revival of their growth indicated fungistatic effect, while absence of any growth indicated fungicidal effect. Experimental Animals In this study, 72 Swiss albino mice (36 males and 36 females; 7–8 weeks old; 20–) and 50 Wistar albino

rats (25 males and 25 females; Inhibitors,research,lifescience,medical 6–8 weeks old; 120–) were used. They were bred in the animal house of the Department of Biochemistry, University of Dschang, Cameroon. The animals were housed two or three per cage in elevated wire mesh cages, and were provided with standard animal food, grower’s mash (Grand Cereals LTD, Jos-Nigeria) and water ad libitum. Acute Toxicity Study This study Inhibitors,research,lifescience,medical was carried out on Swiss albino mice (males and females) as described by Emerson and co-workers.10 A total of 72 mice, 6-8 weeks old were used. The mice of each sex were divided

into 6 subgroups of 6 animals each. Stock solution of crude extract (0.8 g/ml) was prepared using 1% aqueous solution of DMSO. Mice in subgroup 1 (control) Inhibitors,research,lifescience,medical were given (oral gavage) 1% aqueous solution of DMSO (1 ml per BW) while those of subgroups 2, 3, 4, 5 and 6 were administrated 2, 8, 16, 24

and 28 g/kg BW of crude extract, respectively. All the animals were fasted for 18 hours prior to the extract administration. After a single dose administration, Inhibitors,research,lifescience,medical the animals were observed for the first 3 hours for behavioral changes.11 Deaths were counted Inhibitors,research,lifescience,medical for the first 48 hours. The survived mice were closely observed for two weeks, and were monitored daily for behavioral changes, signs of toxicity and the latency of death. The median lethal dose (LD50) was determined by calculation.12 XAV-939 in vitro Sub-Acute Toxicity Study Fifty Wistar albino rats (25 males and 25 females) were used. Animals of each sex were divided into 5 subgroups of 5 animals each. They were kept under the same conditions as described above. about Rats in subgroup 1 (control) were given daily administration of 1% DMSO (1.5 ml per BW) by oral gavage, while those of subgroups 2, 3, 4 and 5 were given 25, 50, 100 and 200 mg/kg BW of the crude extract, respectively for four weeks. All animals were provided with food and water ad libitum. They were then observed for physiological and behavioral changes. Body Weight Trend The body weight of each rat was determined during the acclimatization period, once before the commencement of vehicle or extract administration, once every day during the administration period, and once on the day of the sacrifice.

Whereas, in Japan, ECT was first administered unmodified in 1939

Whereas, in Japan, ECT was first administered unmodified in 1939 and modified 1958 (Chanpattana et al. 2005a), but even so the practice of unmodified ECT in Japan in the 1990s is still profuse (Motohashi et al. 2004; Chanpattana et al. 2005a). In Europe, USA, and Australia/New Zealand, practice was almost entirely

modified ECT and even in Hungary (Gazdag et al. 2004a) anesthesia was obligatory. In several countries, Inhibitors,research,lifescience,medical Chuvash Republic, Russia, Spain, and Japan, the practice of modified ECT was sometimes without muscle relaxants (Ishimoto et al. 2000; Bertolin-Guillen et al. 2006; Golenkov et al. 2010), and even assistants were used to restrain see more extreme motion from the convulsions in Japan (Ishimoto et al. 2000). The unusual practice of muscle relaxants without anesthesia is also undertaken in a few Asian institutions (Chanpattana et al. 2010), and availability and recruitment of anesthesiologists pointed out as a problem

both in Inhibitors,research,lifescience,medical Asia and Europe (Duffett and Lelliott 1998; Motohashi et al. 2004; Schweder et al. 2011b). On the other hand, Wales has no shortage of anesthesiologists Inhibitors,research,lifescience,medical (Duffett et al. 1999). Preferred placement of electrodes worldwide (approximately 80%) is BL, as it was from the very beginning (Cerletti and Bini 1938), except for Australia, New Zealand (O’Dea et al. 1991), Norway (Schweder et al. 2011b), Vienna (Tauscher et al. 1997), Munich (Baghai Inhibitors,research,lifescience,medical et al. 2005), and the Netherlands (van Waarde et al. 2009) where UL is the first choice, but they also use both types. Brief-pulse wave current devices appear widespread world widely. Many countries (Scandinavia, Australia, and New Zealand) adhere to brief-pulse wave and UL electrode placement as first choice (Fink 2001; Rose et al. 2003; Shorter 2009), no doubt due to the reported trade-off effect between effectiveness and memory impairment (The UK ECT Review Group 2003), but switch to BL when the clinical response is judged as too poor. In spite of sine-wave current being declared unjustified

by guidelines today (American Psychiatric Inhibitors,research,lifescience,medical Association 2001), it still occurs in Europe (14–52%) (Muller et al. 1998; Gazdag et al. 2004a, 2009a; Nelson 2005; Bertolin-Guillen et al. 2006; Sienaert et al. 2006), Asia (30–58%) (Chanpattana et al. 2005a, b, 2010), and PDK4 USA (2%) (Prudic et al. 2001). Previous literature indicates a predominance of patients receiving ECT in Western countries to be elderly female with affective disorder (unipolar/bipolar depression) (Reid et al. 1998; Glen and Scott 1999; Fergusson et al. 2003; Baghai et al. 2005; Moksnes et al. 2006), as is also confirmed by this review, and also in Hong Kong (Chung et al. 2009). Except for age being younger, female and depression predominance was also the case for Saudi Arabia (Alhamad 1999) and Pakistan (Naqvi and Khan 2005).

This clearly explains why the distance between species cannot be

This clearly explains why the distance between species cannot be measured only by sequence comparisons. Based on such calculations we can indeed conclude that we are closer to chimpanzees than to mice (we know this from other physical traits), but this does not mean that we are 98.77% chimpanzee and 80% mouse. An important message here is Inhibitors,research,lifescience,medical that what counts is not the number of mutations, but where they occur – where they hit the genome. Mutations in regulatory domains are not identical, in term of consequences, to mutations in coding sequences. Their effects will vary depending

on the type of gene under their control; for example a developmental gene or a gene encoding a protein of little physiological importance, eg, eye color. Also in the case of coding sequences, some mutations can have important evolutionary consequences, as will be illustrated in the case of FoxP2, a transcription factor that Inhibitors,research,lifescience,medical may have played a role in the evolution of animal behavior and INCB28060 cell line communication.12 Finally, it must be underlined that, also for coding sequences, some mutations are silent and others possibly dramatic, depending on the similarities or differences between the normal amino acid and the new Inhibitors,research,lifescience,medical one

resulting from the mutation. Technically speaking, some substitutions are synonymous and others nonsynonymous. Point mutations accounting for the 1.23% difference are not the end of the story If one considers the genetic diversity of our species, and its approximate date of appearance (200 000 years ago, more or less), it can be deduced that the founding population was composed of

approximately 10 000 individuals. The fact that we have the same number of genes as the chimpanzees from whom we separated 7 million Inhibitors,research,lifescience,medical years ago leads to the conclusion that mutations in regulatory domains have been decisive. For example, a mutation in a gene regulating the division of neural stem cells in a given region of the brain neuroepithelium will specifically modify the size of this region.10,13 The conclusion is evident: the famous 1.23% implies Inhibitors,research,lifescience,medical sequences of considerable qualitative importance, including regulatory elements of isothipendyl developmental genes, with potentially spectacular effects on the morphology and physiology of the organisms. Most importantly, the differences are not limited to the 1.23% of point mutations, as one must add all genomic deletions and insertions, plus the duplications that modify gene dosage. Given the size of the human genome, 1.23% translates into 30 million point mutations (a number not to be underestimated), to which one should add duplications, insertions, and deletions (between man and chimpanzee, gene copy numbers differ by more than 6%). Taken together, mutations, duplications, insertions, and deletions modify the global chromatin structure, and thus the regulation of gene expression.

Through venous approach via right

Through venous approach via right femoral vein, 7 French guiding catheter click here passed right atrium and innominate vein approaching to LSVC. The proximal and distal part of the LSVC were measured 9.8 and 9.6 mm, respectively by angiography (Fig. 3). The abnormal connection between LSVC and LSPV was closed

using the Amplatzer® Vascular Plug II (diameter = 12 mm; St. Jude Medical, St. Paul, MN, USA) (Fig. 4). After checked up size of PFO by sizing balloon, transcatheter PFO Inhibitors,research,lifescience,medical closure with Amplatzer® PFO occluder (diameter = 25 mm; St. Jude Medical, St. Paul, MN, USA) was also performed (Fig. 5). Follow-up echocardiogram showed complete occlusion of flow through the LSVC and PFO. Fig. 3 Angiogram. Abnormal connection of LSVC to left atrium was shown on angiogram. LSVC: left superior vena cava, LUPV: left upper pulmonary vein. Fig. 4 Abnormal drainage of left superior vena cava and left upper pulmonary vein was closed using the Amplatzer® vascular plug II. Fig. 5 Transcatheter PFO

closure with Amplatzer® PFO occluder. PFO: patent foramen ovale. Discussion Inhibitors,research,lifescience,medical In recent years, transthoracic echocardiogram (TTE) or transesophageal echocardiography in patients who have had TIA or stroke has become a routine assessment. Inhibitors,research,lifescience,medical A contrast echocardiography is usually performed by injecting microbubbles through the peripheral intravenous (IV) line, and acted the Valsalva maneuver to determine the presence of right-to-left shunting across the PFO. In our patient, the IV line was first started on the right arm and the contrast echocardiography was performed,

which proved the presence of PFO. On contrast echo conducted on Rt. Inhibitors,research,lifescience,medical arm, the enhancement was seen at not only Rt. side of heart, but also Lt. side. On careful review by an experienced doctor, small Inhibitors,research,lifescience,medical amount of direct flow into the LA was recognized. Another IV line was started on the left arm of the patient. The contrast echo was done as a same way on Lt. arm. On repeated contrast echocardiography, massive amount of microbubbles draining straight to LA was detected. Heart CT was performed to determine the precise LSVC drainage, resulting persistent LSVC persistent LSVC connection to LSPV was diagnosed. Incidence of persistent LSVC is 0.5% of the general population and increased to 4.3% in patients with congenital heart disease.6),7) Persistent LSVC draining into the coronary sinus and MRIP the right atrium is of no hemodynamic significance. But persistent LSVC draining directly or through an unroofed coronary sinus into the left atrium represents the same risks as all other lesions with right-to-left shunt and forms a substrate for paradoxical embolism. If complications related to the right-to-left shunt occur, correction is indicated.8) In this case of our patient, relatively young age at the time of stroke development probably indicates that both PFO and persistent LSVC was the cause of paradoxical embolism.

This was attributable in subsequent analyses to possibly higher<

This was attributable in subsequent analyses to possibly higher

doses of aspirin used in North America. Thus, the FDA issued a “Boxed Warning” indicating that aspirin daily maintenance doses of >100 mg decrease the effectiveness of ticagrelor. The FDA also cautioned against its use in patients with active bleeding or a history of intracranial hemorrhage and advocated a Risk Evaluation and Mitigation Strategy, a plan to help ensure that the benefits of ticagrelor outweigh its risks. Ticagrelor was incorporated into Inhibitors,research,lifescience,medical the 2011 ESC guidelines for ACS,9 which recommended the use of an oral P2Y12 inhibitor (prasugrel or ticagrelor) as a second-line agent in preference to clopidogrel and intravenous GP IIb/IIIa inhibitors (in contradistinction to the ACCF/AHA guidelines). It is important

to note that the 2012 ACCF/AAHA guidelines update did not endorse one antiplatelet over the other, but rather advocated the use of clopidogrel, Inhibitors,research,lifescience,medical prasugrel (after coronary angiography is done and patients are RG7422 purchase referred to PCI), ticagrelor, or an intravenous glycoprotein (GP) IIb/IIIa inhibitor as a second-line antiplatelet therapy that should be added to aspirin background therapy. Higher-Dose Regimen of Clopidogrel Inhibitors,research,lifescience,medical The guideline proposed the use of a higher-dose regimen of clopidogrel (600-mg loading dose, followed by a 150-mg daily dose for 6 days and a 75-mg daily dose thereafter) as a reasonable strategy in UA/NSTEMI patients undergoing PCI (Table I).1 This was based on the PCI cohort substudy from the CURRENT-OASIS 7 trial, which included a total Inhibitors,research,lifescience,medical of 17,232 patients (69% of the overall CURRENT population) and in which double dosing of clopidogrel was associated with a 15% statistically significant lower 30-day composite of CV death, MI, or stroke

as well as lower subacute ST rates.6 Inhibitors,research,lifescience,medical This was, however, associated with increased major and severe bleeding (CURRENT study definition) and the need for blood transfusion. also It is important to note that the findings of this prespecified short-term subgroup analysis are derived from a larger trial that did not meet its primary outcome; there was no benefit associated with the higher-dose regimen of clopidogrel in the overall CURRENT cohort, which included PCI- and medially-managed UA/NSTEMI patients, and as such its findings should be interpreted with caution. Role of Genotyping and Platelet Aggregation Assays The 2012 guidelines advocated the use of platelet function testing in UA/NSTEMI patients treated with a thienopyridine or genotype testing in those treated with clopidogrel in particular, provided the results of either testing alter patients’ medical management (Table 1).

All patients were descended from at least two generations of Cauc

All patients were descended from at least two generations of Caucasians, and were interviewed by trained psychiatrists or psychologists using the French version of the Diagnostic Interview for Genetic Studies (DIGS) or the Mini International Neuropsychiatric Interview (MINI) (Nurnberger et al. 1994; Preisig et al. 1999). Almost all bipolar

patients were diagnosed as BD-I, except for subjects identified as BP-II (98% of BP-I). Controls were recruited from blood donors in Geneva Inhibitors,research,lifescience,medical Hospitals (Geneva, Switzerland) and met the criteria of the DIGS questionnaire for their inclusion. The mean age (±SD) was 35 ± 10, 42 ± 11, and 44 ± 12 years, for SZ, BD, and Controls, respectively. Inhibitors,research,lifescience,medical The female composition was 40%, 50%, and 44%, for SZ, BD, and Controls, respectively. Table 1 Demographic data Genotyping DNA was extracted from peripheral blood leukocytes by using of the Nucleon BACC 2 kit (Amersham Biosciences, GE Healthcare, Glatbrugg, Switzerland). The -432C>T (rs3813065) was genotyped by restriction find more digestion with the enzyme SwaI as described by Stopkova et al. (2004). The dinucleotide repeat polymorphism was identified Inhibitors,research,lifescience,medical by the UCSC genome browser (March 2006). This microsatellite is located on chromosome 18,

between 939, 492, 926–939, 492, 962 bp. This genetic variant was amplified by polymerase chain reaction (PCR) on a 96-well plate thermal cycler (Biometra, Goettingen, Germany). The following primers were used: 5′-ACCTTTTCCTACTTCAATTCACA-3′ type forward and 5′-TCCTAGAGAAGAGGTATGATGATGG-3′ Inhibitors,research,lifescience,medical type reverse. PCR reaction was carried out with 100 ng of genomic DNA using Hot Star Taq DNA polymerase (Eurobio, Brunschwig, Basel, Switzerland) in a 25 mL reaction mix containing 1× buffer (Tris-Cl, KCl, (NH4)2SO4, 15 mM MgCl2; pH 8.7), 0.10 mM dNTPs, 0.03 mM MgCl2,

0.02 mM of each primer, 1U Taq polymerase. Amplification conditions were as follows: 95°C for 5 Inhibitors,research,lifescience,medical min, 25 cycles of 92°C for 30 sec, 60°C for 30 sec, and 72°C for 30 sec. PCR products were analyzed by electrophoresis on a 10% polyacrylamide gel at 250 V for 150 min and visualized with ethidium bromide. Allele (CA)11 was 88 bp, allele (CA)12 was 90 bp, allele (CA)13 was 92 bp, allele (CA)14 was 94 bp, allele (CA)16 was 98 bp, allele (CA)17 was 100 bp, and allele (CA)18 was 102 bp. The Oxymatrine SNP rs8095411 was identified by the Ensembl data bank and explored by high-resolution melt (HRM) assay using a Rotor-Gene 6000 instrument (Corbett Life Science, Australia). Amplicon sequence was analyzed by the Poland melting software program to predict melting behavior ( The secondary structures were checked by DINAMelt ( = DINAMelt/Two-state-folding). The following primers were used: 5′-GAGCCTGCAAAAACTCAACA-3′ type forward and 5′-AACCCAGCTGTCAGGGAATA-3′ type reverse.

It is likely not to change our understanding, and may be an imped

It is likely not to change our understanding, and may be an impediment to better identification of subjects and treatments. An example of an essentialist identification is Hepatitis B or C. Here, there is no

link to symptoms or signs – just to the cause. The doctor’s skill then consists in identifying the causal disease and prescribing the appropriate treatment. This concept of disease is not yet applicable Inhibitors,research,lifescience,medical in a broad sense to psychiatry, because much less is known, and causation is likely to be multifactorial. However, as evidence of causation develops, an essentialist mentality can move the field forward. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) points out that “there is no assumption that each category of mental disorder is a completely discrete entity with absolute boundaries dividing it from other Inhibitors,research,lifescience,medical mental disorders or from no mental disorder” (p 21),10 but the mere fact that a diagnostic concept is listed, official,

and provided with a precise definition makes Inhibitors,research,lifescience,medical it appear robust and specific. Definitions are stated to become codified and reified without an examination of the fundamental validity. Robins and Guze11 proposed formal criteria for establishing the validity of psychiatric diagnoses; however few of the entities in DSM meet these criteria. As Kendell and others have pointed out, it is likely that the concept of a nominalist description of disease in the psychiatric context as a distinct entity may not be relevant.6 One of the hallmarks for symptom- and course-based identification is to demonstrate points of nonoverlap between similar syndromes.9,11 The points of rarity between psychiatric diseases defined Inhibitors,research,lifescience,medical in a nominalist tradition are not as distinct as one would like. On the other hand, an essentialist classification

may be very relevant. We have recently noted a Inhibitors,research,lifescience,medical system for defining a condition as a disease. Criteria for defining disease The first and obvious criterion is that the condition should be one that leads to a risk for adverse outcomes – either mortality or Sepantronium Bromide cell line functional impairment.12 The second is where an identifiable characteristic genetic or environmental factor or pathology can be much clearly defined. This characteristic should separate the entity from similar entities, in terms of at least one of the following criteria: Clinical symptoms Course and outcome Familial pattern Treatment response. The differentiation should be clinically significant. Clinical significance may have to be adjudicated by collective groups. Trie failure to separate may change over time as additional information is developed, and may go through a stage where the characteristic is considered as a subentity.12,13 Is the time right to ask whether there are potential essentialist conditions relevant to depression? I think it is, and I would like to introduce the notion of two such categories.

23,24 In short, the reduced emotional responsiveness of individua

23,24 In short, the reduced emotional responsiveness of individuals with elevated

psychopathic traits could be a secondary consequence of heightened top-down attentional control to non-emotional stimulus features.25 In recent studies in adults with psychopathy, Newman and colleagues manipulated attention either towards the threat-relevant component of a stimulus array or away Inhibitors,research,lifescience,medical from this component and examined fear-potentiated startle (FPS).3,4 In each of these studies, psychopathy scores were significantly inversely related to FPS under conditions that required participants to focus on a threat-irrelevant dimension of stimuli. In contrast, psychopathy scores were unrelated to FPS when attention was focused on the threat-relevant dimension. These studies provide important support for the suggestion that it is an attentional abnormality, rather than a problem in emotional responding, that is central

to an understanding of psychopathy. Given the literature on the interaction of top-down attentional Inhibitors,research,lifescience,medical control and emotional responding,23,24 these data should suggest that psychopathy is related to enhanced recruitment of regions implicated in top-down attentional control (ie, dorsomedial and lateral frontal and parietal cortices26). The stronger these Inhibitors,research,lifescience,medical are recruited (as a function of psychopathy), the stronger the priming of threat irrelevant stimulus dimensions, the weaker the representation of threat relevant stimulus dimensions following Caspase inhibitor representational competition, and the weaker the emotional response. However, there are at least five reasons to be cautious. Inhibitors,research,lifescience,medical First, while these are correlational studies within a forensic sample, and thus studies where IQ could not be matched across groups, it remains critical to show that IQ did not correlate with psychopathy level. Otherwise the results might reflect the influence of IQ rather than psychopathy. However, Inhibitors,research,lifescience,medical this matching was not done. Second, only the individuals with psychopathy showed an impact of the attentional manipulation. Individuals low in psychopathy showed no differentiation in their fear-potentiated startle as a function of whether attention was directed ADAMTS5 towards

or away from threat-relevant stimulus features. It is currently unclear why this paradigm contrasts with other work showing that manipulations of attention do have an impact on emotional responding in healthy individuals.23,24 Third, while superior recruitment of top-down attentional control systems would result in reduced emotional responses to emotional stimuli that are not the focus of attention, there are no indications of increased recruitment of such systems in the studies showing reduced amygdala responses to emotional stimuli in adults with psychopathy. Fourth, several studies have shown reduced FPS in individuals with psychopathy to environmental threats in the absence of task demands to attend to other stimulus features.

However, there are some clear indications how certain

However, there are some clear indications how certain receptor actions might be involved in both the beneficial and adverse effects of these drugs, as well as some intriguing potential mechanisms as yet inadequately explored. Effects on bipolar symptoms The neuronal dysfunction that underlies mania and manic episodes remain obscure, even more so that the psychosis of schizophrenia. Inhibitors,research,lifescience,medical It is generally considered that the primary SGC-CBP30 cost antipsychotic mechanism

in schizophrenia involves antagonist action at the dopamine D2 receptor; occupancy of this receptor in the striatum correlates best with relief of positive symptoms of the disease [Agid et al. 2007]. Given the similar efficacy of the atypical antipsychotic drugs in treating mania, an efficacy extending to the conventional antipsychotic haloperidol, which is especially effective Inhibitors,research,lifescience,medical [Tohen and Vieta, 2009; Cipriani et al. 2011], it seems likely that this mechanism

also underlies the anti-manic effect of all antipsychotic drugs. Mania is not inevitably psychosis, although it can develop psychotic features, and this suggests that the effects of the drugs are not solely ‘antipsychotic’ but are, using an outmoded description, ‘major tranquillizers’. Current hypotheses of antipsychotic action address the role of dopamine hyperfunction Inhibitors,research,lifescience,medical in the aberrant attribution of salience model of psychosis [Kapur, 2003]. Whether this salience dysregulation syndrome can extend to include mania is unclear [van Os, 2009]. However, of the other subjective effects of antipsychotic-induced dopamine blockade, a reduction in motivational drive [Henry et al. 2006; Mavrikaki et al. 2010] is one consequence Inhibitors,research,lifescience,medical that could result in attenuation of manic behaviour. Whatever the neuropsychological mechanism, the efficacy of the relatively selective high activity Inhibitors,research,lifescience,medical D2 antagonist haloperidol indicates that dopamine

D2 antagonism alone, or partial agonism/antagonism in the case of aripirazole, is a sufficient pharmacological mechanism for the relief of acute mania common to all antipsychotic drugs. The role, if any, of the D3 receptor no in these processes is as yet unclear, and we still have no clear understanding of the influence of the relatively higher affinities for this dopamine D2-like receptor subtype shown by asenapine and ziprasidone. What is likely to differentiate the antipsychotics in the treatment of bipolar disorder will therefore relate not solely to antimanic effects but also to other aspects of treatment relating to symptom relief and side effects. The other side of the bipolar disorder coin is depression. Of the atypicals, quetiapine is licensed for bipolar depression, while others including asenapine [Szegedi et al. 2011], have demonstrated the improvement of depressive symptoms in patients with manic episodes.