Acute desipramine restores presynaptic cortical defects in murine experimental autoimmune encephalomyelitis by suppressing central CCL5 overproduction

Background and Purpose

Altered glutamate exocytosis and cAMP production in cortical terminals of experimental autoimmune encephalomyelitis (EAE) mice occur at the early stage of disease (13 days post-immunization, d.p.i.). Neuronal defects were paralleled by overexpression of the central chemokine CCL5 (also known as RANTES), suggesting it has a role in presynaptic impairments. We propose that drugs able to restore CCL5 content to physiological levels could also restore presynaptic defects. Because of its efficacy in controlling CCL5 overexpression, desipramine (DMI) appeared to be a suitable candidate to test our hypothesis.

Experimental Approach

Control and EAE mice at 13 d.p.i. were acutely or chronically administered DMI and monitored for behaviour and clinical scores. Noradrenaline and glutamate release, cAMP, CCL5 and TNF-α production were quantified in cortical synaptosomes and homogenates. Peripheral cytokine production was also determined.

Key Results

Noradrenaline exocytosis and α₂-adrenoeceptor-mediated activity were unmodified in EAE mice at 13 d.p.i. when compared with control. Acute, but not chronic, DMI reduced CCL5 levels in cortical homogenates of EAE mice at 13 d.p.i., but did not affect peripheral IL-17 and TNF-α contents or CCL5 plasma levels. Acute DMI caused a long-lasting restoration of glutamate exocytosis, restored endogenous cAMP production and impeded the shift from inhibition to facilitation of the CCL5-mediated control of glutamate exocytosis. Finally, DMI ameliorated anxiety-related behaviour but not motor activity or severity of clinical signs.

Conclusions

We propose DMI as an add-on therapy to normalize neuropsychiatric symptoms in multiple sclerosis patients at the early stage of the disease.     

Dimensions and disorder specificity of impulsivity in pathological gambling

Impulsivity is a core characteristic of pathological gambling (PG), even though the underlying structure and disorder specificity is unclear. This study aimed to explore different dimensions of impulsivity in a clinical sample including PG. Furthermore, we aimed to test which alterations of the impulsivity-related dimensions are disorder specific for PG. Participants were individuals diagnosed with PG (n = 51) and two groups also characterized by various impulsive behaviors: an alcohol dependence (AD; n = 45) and a Gilles de la Tourette syndrome (GTS; n = 49) group. A healthy control (HC; n = 53) group was recruited as comparison group. A comprehensive assessment was used including impulsivity-related and antipodal parameters of the Stop Signal Task, Stroop Task, Tower of London Task, Card Playing Task, Iowa Gambling Task and the Barratt Impulsiveness Scale-11. Principal axis factor analysis revealed four impulsivity-related dimensions that were labeled ‘self-reported impulsivity’, ‘prepotent response impulsivity’, ‘choice impulsivity’ and ‘motor impulsivity’. The PG group scored significantly higher on all four dimensions compared to the HC group. In contrast, the PG group did not differ on any of the dimensions from the AD or the GTS group, except for ‘choice impulsivity’ where the PG group exhibited higher factor scores compared to the GTS group. Altogether, PG is associated with generally heightened impulsivity profiles compared to a HC group, which may be further used for intervention strategies. However, heightened scores in the impulsivity dimensions are not disorder specific for PG. Further research on shared or different underlying mechanisms of these overlapping impulsivity impairments is necessary.     

The first report on Amphipoda from Marian Cove,King George Island,Antarctic

This is a first account on amphipods from Marian Cove in Maxwell Bay, near the King Sejong Station, King George Island, the Antarctic. We have conducted a survey in 14 localities in the shallow sublittoral zone. A total of 22 amphipod species belonging to 12 families were identified. Six of these species were new for the whole Maxwell Bay. Our findings increase the amphipod fauna of Maxwell Bay from 55 to 61 species. The dominant species in the shallow sublittoral zone of Marian Cove were: Cheirimedon femoratus and Gondogeneia antarctica, followed by Bovallia gigantea, Orchomenella cf. ultima, Paradexamine fissicauda, Prostebbingia brevicornis, Pariphimedia integricauda, and Jassa wandeli.     

Recovery‐oriented policy and care systems in the UK and USA

The concept of recovery has been an influence on addicted individuals for many decades. But only in the past 15 years has the concept had a purchase in the world of public policy. In the USA, federal and state officials have promulgated policies intended to foster ‘recovery‐oriented systems of care’ and have ratified recovery‐supportive laws and regulations. Though of more recent vintage and therefore less developed, recovery policy initiatives are also being implemented in the UK. The present paper describes recovery‐oriented policy in both countries and highlights key evaluations of the recovery‐oriented interventions. [Humphreys K, Lembke A. Recovery‐oriented policy and care systems in the UK and USA. Drug Alcohol Rev 2014;33:13–18]     

Is there a problem with the status quo? Debating the need for standalone ethical guidelines for research with people who use alcohol and other drugs

In 2011, the Australian National Health and Medical Research Council (NHMRC) initiated an inquiry to determine whether there is a need for expanded ethical guidance in the form of a discrete guidance document for alcohol and other drug (AOD) research. An issues paper was developed to frame the inquiry. AOD researchers, Human Research Ethics Committees and others were invited to discuss whether there are distinctive ethical issues facing researchers and Human Research Ethics Committees in the AOD setting. Based on the public submissions, the NHMRC recommended that no AOD research‐specific guidance is required. The inquiry and the NHMRC decision were not widely publicized, and we feel there is a need for further discussion. In order to do so, we have analysed the public inquiry submissions and described the central themes. Few submissions in the inquiry explicitly agreed AOD research warrants a specific guidance framework. Most were concerned that the NHMRC issues paper unfairly targeted people who use drugs as complex research participants. The inquiry highlights tensions around research governance and ethics review boards dealing with illicit and stigmatised behaviours. While we agree that a specific guidance framework for AOD research is not needed and could potentially be harmful and restrictive, we are concerned that the wholesale rejection of a guidance framework has closed the door to much needed debate. There remains, we argue, a need for alternative strategies and tools to support ethical research, inform and streamline institutional ethics approval, and engage and protect participants. [Olsen A, Mooney‐Somers J. Is there a problem with the status quo? Debating the need for standalone ethical guidelines for research with people who use AODs. Drug Alcohol Rev 2014;33:637‐642]     

Review of the Applications of Biomedical Compositions Containing Hydroxyapatite and Collagen Modified by Bioactive Components

Regenerative medicine is becoming a rapidly evolving technique in today’s biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegradable, biocompatible, and correlated with macromolecules, which facilitates their incorporation into inorganic materials. This review article provides extensive knowledge on HAp and collagen-containing compositions modified with drugs, bioactive components, metals, and selected nanoparticles. Such compositions consisting of HAp and collagen modified with various additives are used in a variety of biomedical applications such as bone tissue engineering, vascular transplantation, cartilage, and other implantable biomedical devices.     

Research on Reduction of Selected Iron-Bearing Waste Materials

During the steel production process, nearly twice as many input materials are used as compared to finished products. This creates a large amount of post-production waste, including slag, dust, and sludge. New iron production technologies enable the reuse and recycling of metallurgical waste. This paper presents an investigation on the reduction of selected iron-bearing waste materials in a laboratory rotary furnace. Iron-bearing waste materials in the form of dust, scale, and sludge were obtained from several Polish metallurgical plants as research material. A chemical analysis made it possible to select samples with sufficiently high iron content for testing. The assumed iron content limit in waste materials was 40 wt.% Fe. A sieve analysis of the samples used in the subsequent stages of the research was also performed. The tests carried out with the use of a CO as a reducer, at a temperature of 1000 °C, allowed to obtain high levels of metallization of the samples for scale 91.6%, dust 66.9%, and sludge 97.3%. These results indicate that in the case of sludge and scale, the degree of metallization meets the requirements for charge materials used in both blast furnace (BF) and electric arc furnace (EAF) steelmaking processes, while in the case of reduced dust, this material can be used as enriched charge in the blast furnace process. Reduction studies were also carried out using a gas mixture of CO and H₂ (50 vol.% CO + 50 vol.% H₂). The introduction of hydrogen as a reducing agent in reduction processes meets the urgent need of reducing CO₂ emissions. The obtained results confirm the great importance and influence of the selection of the right amount of reducer on the achievement of a high degree of metallization and that these materials can be a valuable source of metallic charge for blast furnace and steelmaking processes. At an earlier stage of the established research program, experiments of the iron oxides reduction from iron-bearing waste materials in a stationary layer in a Tammann furnace were also conducted.