Anxiolytic and anti-stress effects of acute administration of acetyl-L-carnitine in zebrafish

Studies have suggested that oxidative stress may contribute to the pathogenesis of mental disorders. In this context, molecules with antioxidant activity may be promising agents in the treatment of these deleterious conditions. Acetyl-L-carnitine (ALC) is a multi-target molecule that modulates the uptake of acetyl-CoA into the mitochondria during fatty acid oxidation, acetylcholine production, protein, and membrane phospholipid synthesis, capable of promoting neurogenesis in case of neuronal death. Moreover, neurochemical effects of ALC include modulation of brain energy and synaptic transmission of multiple neurotransmitters, including expression of type 2 metabotropic glutamate (mGlu2) receptors. The aim of this study was to investigate the effects of ALC in zebrafish by examining behavioral and biochemical parameters relevant to anxiety and mood disorders in zebrafish. ALC presented anxiolytic effects in both novel tank and light/dark tests and prevented the anxiety-like behavior induced by an acute stressor (net chasing). Furthermore, ALC was able to prevent the lipid peroxidation induced by acute stress in the zebrafish brain. The data presented here warrant further investigation of ALC as a potential agent in the treatment of neuropsychiatric disorders. Its good tolerability also subsidizes the additional studies necessary to assess its therapeutic potential in clinical settings

Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications

Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

<p>Abstract</p> <p>Background</p> <p>Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.</p> <p>Methods</p> <p>We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.</p> <p>Results</p> <p>The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.</p> <p>Conclusion</p> <p>We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.</p

Effects of N-acetylcysteine on amphetamine-induced sensitization in mice

Objective: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. Methods: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. Results: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Conclusion: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification

Validation of the Spanish Version of the ICECAP-O for Nursing Home Residents with Dementia

Background Measurement of health-related quality of life (HRQoL) is important for a chronic disease, such as dementia, which impairs the quality of life of affected patients in addition to their length of life. This is important in the context of economic evaluations when interventions do not (only) affect HRQoL and these other factors also affect overall quality of life. Objective To validate the Spanish translation of the ICECAP-O's capability to measure Health-related quality of life in elderly with dementia who live in nursing homes. Method Cross-sectional study. For 217 residents living in 8 Spanish nursing homes, questionnaires were completed by nursing professionals serving as proxy respondents. We analyzed the internal consistency and other psychometric properties. We investigated the convergent validity of the ICECAP-O with other HRQoL instruments, the EQ-5D extended with a cognitive dimension (EQ-5D+C), the Alzheimer's Disease Related Quality of Life (ADRQL) measures, and the Barthel Index measure of activities of daily living (ADL). Results The ICECAP-O presents satisfactory internal consistency (alpha 0.820). The factorial analysis indicated a structure of five principal dimensions that explain 66.57% of the total variance. Convergent validity between the ICECAP-O, EQ-5D+C, ADRQL, and Barthel Index scores was moderate to good (with correlations of 0.62, 0.61, and 0.68, respectively), but differed between dimensions of the instruments. Discriminant validity was confirmed by finding differences in ICECAP-O scores between subgroups based on ADL scores (0.70 low, 0.59 medium, and 0.39 high level care), dementia severity (0.72 mild, 0.63 medium, and 0.50 severe), and ages (0.59 below 75 years and 0.84 above 75 years). Conclusions This study presented the first use of a Spanish version of the ICECAP-O. The results indicate that the ICECAP-O appears to be a reliable Health-related quality of life measurement instrument showing good convergent and discriminant validity for people with dementia

The SAGEX Review on Scattering Amplitudes

This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.Comment: 15 pages, overview articl

Leaching material from Antarctic seaweeds and penguin guano affects cloud-relevant aerosol production

Within the Southern Ocean, the greatest warming is occurring on the Antarctic Peninsula (AP) where clear cryospheric and biological consequences are being observed. Antarctic coastal systems harbour a high diversity of marine and terrestrial ecosystems heavily influenced by Antarctic seaweeds (benthonic macroalgae) and bird colonies (mainly penguins). Primary sea spray aerosols (SSA) formed by the outburst of bubbles via the sea-surface microlayer depend on the organic composition of the sea water surface. In order to gain insight into the influence of ocean biology and bio-geochemistry on atmospheric aerosol, we performed in situ laboratory aerosol bubble chamber experiments to study the effect of different leachates of biogenic material - obtained from common Antarctic seaweeds as well as penguin guano - on primary SSA. The addition of different leachate materials on a seawater sample showed a dichotomous effect depending on the leachate material added - either suppressing (up to 52%) or enhancing (22–88%) aerosol particle production. We found high ice nucleating particle number concentrations resulting from addition of guano leachate material. Given the evolution of upper marine polar coastal ecosystems in the AP, further studies on ocean-atmosphere coupling are needed in order to represent the currently poorly understood climate feedback processes.The study was further supported by the Spanish Ministry of Economy through project PI-ICE (no. CTM 2017–89117-R) and the Ramon y Cajal fellowship (no. RYC-2012-11922). This work acknowledges the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S). The National Centre for Atmospheric Science (NCAS) Birmingham group is funded by the UK Natural Environment Research Council. We gratefully acknowledge the funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Projektnummer 268020496–TRR 172) within the Transregional Collaborative Research Center “ArctiC Amplification: Climate Relevant Atmospheric and SurfaCe Processes, and Feedback Mechanisms (AC)3” in subproject B04.Peer reviewe

sodC-Based Real-Time PCR for Detection of Neisseria meningitidis

Real-time PCR (rt-PCR) is a widely used molecular method for detection of Neisseria meningitidis (Nm). Several rt-PCR assays for Nm target the capsule transport gene, ctrA. However, over 16% of meningococcal carriage isolates lack ctrA, rendering this target gene ineffective at identification of this sub-population of meningococcal isolates. The Cu-Zn superoxide dismutase gene, sodC, is found in Nm but not in other Neisseria species. To better identify Nm, regardless of capsule genotype or expression status, a sodC-based TaqMan rt-PCR assay was developed and validated. Standard curves revealed an average lower limit of detection of 73 genomes per reaction at cycle threshold (Ct) value of 35, with 100% average reaction efficiency and an average R2 of 0.9925. 99.7% (624/626) of Nm isolates tested were sodC-positive, with a range of average Ct values from 13.0 to 29.5. The mean sodC Ct value of these Nm isolates was 17.6±2.2 (±SD). Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative Nm isolates, and 98.9% (176/178) of these were detected by sodC rt-PCR. The assay was 100% specific, with all 244 non-Nm isolates testing negative. Of 157 clinical specimens tested, sodC detected 25/157 Nm or 4 additional specimens compared to ctrA and 24 more than culture. Among 582 carriage specimens, sodC detected Nm in 1 more than ctrA and in 4 more than culture. This sodC rt-PCR assay is a highly sensitive and specific method for detection of Nm, especially in carriage studies where many meningococcal isolates lack capsule genes