Introduction
Three generations of antipsychotics, all of which are based on the dopaminergic hypothesis of schizophrenia, are available for clinical use. Still, more than 66% of the patients ...diagnosed with schizophrenia spectrum disorders (SSD) could not achieve remission. Also, the glutamatergic hypothesis of schizophrenia is supported by translational models of this disease, even if the antipsychotics derived from this conceptual framework are not yet available on the market. However, the need for new pathogenesis models for schizophrenia and new generations of antipsychotics is acute, therefore, an exploration of the antipsychotics in the pipeline could be helpful in understanding the current stage of research in schizophrenia.
Objectives
To assess the evidence supporting the potential benefits of new antipsychotics in the pipeline.
Methods
A literature review was performed through the main electronic databases PubMed, Cochrane, Clarivate/Web Of Science, and EMBASE) and clinical trials repositories (US National Library of Medicine and World Health Organization Clinical Trials Registry Platform) using the search paradigm “antipsychotics” AND “schizophrenia” AND “non-dopaminergic” AND “non-glutamatergic”. All papers published between January 2010 and September 2022 were included.
Results
Xanomeline/trospium (xanomeline is a muscarinic M1/M4 receptor agonist at the central nervous system, while trospium limits its peripheral effects) was efficient for schizophrenia in one phase III clinical trial. Pimavanserin (a selective 5HT2A inverse agonist and antagonist) was efficient in improving negative symptoms of schizophrenia in a phase II trial. Roluperidone (a 5HT2A and σ2 receptor antagonist) has been associated with favorable results in phase III clinical trials, mainly on negative symptoms of schizophrenia. SEP-363856 is a TAAR-1 agonist and 5HT1A agonist, currently explored in phase III clinical trials for schizophrenia. MK-8189 is a phosphodiesterase 10A inhibitor, investigated in phase III clinical trials for schizophrenia.
Conclusions
Based on the retrieved data in the literature, multiple mechanisms, other than glutamatergic and dopaminergic pathways, are currently being investigated, and many of the antipsychotics based on these mechanisms are in the advanced stage of research. This is important not only for the clinical need to find more efficient and tolerable drugs for patients with schizophrenia but also because they may shed new light on the pathogenesis of this disease.
Disclosure of Interest
None Declared
Assessing the possible biological effects of exposure to low doses of ionizing radiation (IR) is one of the prime challenges in radiation protection, especially in medical imaging. Today, ...radiobiological data on cone beam CT (CBCT) related biological effects are scarce. In children and adults, the induction of DNA double strand breaks (DSBs) in buccal mucosa cells and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and antioxidant capacity in saliva samples after CBCT examination were examined. No DNA DSBs induction was observed in children nor adults. In children only, an increase in 8-oxo-dG levels was observed 30 minutes after CBCT. At the same time an increase in antioxidant capacity was observed in children, whereas a decrease was observed in adults. Our data indicate that children and adults react differently to IR doses associated with CBCT. Fully understanding these differences could lead to an optimal use of CBCT in different age categories as well as improved radiation protection guidelines.
Cone beam CT (CBCT) for dentomaxillofacial paediatric assessment has been widely used despite the uncertainties of the risks of the low-dose radiation exposures. The aim of this work was to ...investigate the clinical performance of different CBCT acquisition protocols towards the optimization of paediatric exposures. Custom-made anthropomorphic phantoms were scanned using a CBCT unit in six protocols. CT slices were blinded, randomized and presented to three observers, who scored the image quality using a 4-point scale along with their level of confidence. Sharpness level was also measured using a test object containing an air/PMMA e,dge. The effective dose was calculated by means of a customized Monte Carlo (MC) framework using previously validated paediatric voxels models. The results have shown that the protocols set with smaller voxel size (180 µm), even when decreasing exposure parameters (kVp and mAs), showed high image quality scores and increased sharpness. The MC analysis showed a gradual decrease in effective dose when exposures parameters were reduced, with an emphasis on an average reduction of 45% for the protocol that combined 70 kVp, 16 mAs and 180 µm voxel size. In contrast, both "ultra-low dose" protocols that combined a larger voxel size (400 µm) with lower mAs (7.4 mAs) demonstrated the lowest scores with high levels of confidence unsuitable for an anatomical approach. In conclusion, a significant decrease in the effective dose can be achieved while maintaining the image quality required for paediatric CBCT.
Introduction
Mindfulness-based cognitive therapy (MBCT) is a third wave cognitive-behavioral therapy (CBT) that incorporates meditation exercises in the classical, structured intervention. ...Mindfulness has been associated with psychological well-being, and certain symptoms that occur in major depressive disorder (MDD), e.g. worries, ruminations, ideas of incapacity or self-devaluation, are considered potential targets for MBCT.
Objectives
To evaluate the current level of evidence for the MCBT efficacy in MDD.
Methods
A literature serach was performed in the main electronic databases, targeting clinical trials that evaluated in a randomized manner the efficacy of MCBT versus active comparators or placebo in patients with MDD.
Results
MBCT was efficient in a 10-week randomized controlled trial (RCT) versus standard treatment, and it decreased ruminations, increased patients quality of life, mindfulness abilities, and self-compassion. In another randomized, 8-week RCT, MBCT prevented relapses in MDD, with similar rates when compared to psychoeducation and standard treatment. A 26-month follow-up study evidenced the persistence of symptoms improvement detected after 12 months of the trial, when compared to active control group and treatment as usual. MCBT was compared to cognitive therapy in a randomized 8-week trial, and both treatments had similar efficacy in MDD relapse prevention.
Conclusions
MCBT may be an useful adjuvant to the current treatment in acute MDD, but it may also decrease the risk of relapse after psychotherapy termination.
Objective and design
β-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB
2
) receptor and exerts anti-inflammatory effects. In this study, we investigated the ...anti-inflammatory effect of BCP and another CB
2
agonist, GP1a in inflammatory experimental model induced by
Mycobacterium bovis
(BCG).
Methods
C57Bl/6 mice were pretreated orally with BCP (0.5–50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB
2
agonists on neutrophils function was evaluated in vitro.
Results
β-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B
4
(LTB
4
), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB
4
and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB
4
-induced actin polymerization.
Conclusion
These results suggest that the CB
2
receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.
A series of twenty-one quinoline derivatives have been synthesized and evaluated against
Mycobacterium tuberculosis. Three compounds exhibited a significant activity (2.5
μg/mL), which can be ...compared with that of the first line drugs, ethambutol (3.12
μg/mL) and rifampicin (2.0
μg/mL).
A series of twenty-one 7-chloro-4-quinolinylhydrazones (
3a–
u) have been synthesized and evaluated for their in vitro antibacterial activity against
Mycobacterium tuberculosis H
37Rv. The compounds
3f,
3i and
3o were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity (2.5
μg/mL), which can be compared with that of the first line drugs, ethambutol (3.12
μg/mL) and rifampicin (2.0
μg/mL). These results can be considered an important start point for the rational design of new leads for anti-TB compounds.
The present study was carried out to investigate the anti-inflammatory effect of the hexane extract of the leaves from
Clusia nemorosa
G. Mey, called HECn, using carrageenan-induced mice pleurisy and ...cotton pellet-induced mice granuloma. Additionally, the ability of HECn to affect both neutrophil migration as viability was investigated by use of the Boyden chamber assay and flow cytometry, respectively. The HECn significantly inhibited exudation, total leukocytes and neutrophils influx, as well as TNFα levels in carrageenan-induced pleurisy. However, the extract not suppressed the granulomatous tissue formation in the cotton pellet-induced granuloma test. Experiments performed
in vitro
revealed that HECn on human neutrophils inhibited a dose-dependent manner the CXCL1-induced neutrophil chemotaxis. Furthermore, HECn also inhibited the chemoattraction of human neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet activating factor (PAF) in a Boyden chamber. However, this same treatment not was able to induce apoptosis. The results obtained in this study showed that the extract from leaves of
C. nemorosa
possess a potent inhibitory activity in acute model of inflammation, being the effects mediated, in part, by inhibition of neutrophil responsiveness. These results indicate that
C. nemorosa
could be a good source for anti-inflammatory compounds.
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