Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

<p><b>Background and Purpose:</b> The study aim was to assess the effects of magnesium sulfate (MgSO4) administration on white matter damage in vivo in spontaneously hypertensive rats.</p> <p><b>Methods:</b> The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO4 was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.</p> <p><b>Results:</b> ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO4 did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm3; interquartile range, 1.3 to 3.8, vs 1.6 mm3 and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm3 and 0.2 to 0.9 vs 0.3 mm3 and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO4 in both cylinder (left forelimb use, P<0.01 and both-forelimb use, P<0.03 vs vehicle) and walking-ladder (right hindlimb score, P<0.02 vs vehicle) tests.</p> <p><b>Conclusions:</b> ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO4 did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.</p&gt

Disappearance of Azoxystrobin and difenoconazole in green beans cultivated in Souss Massa valley (Morocco)

A study was undertaken to evaluate the degradation behavior and residue levels of azoxystrobin and difenoconazole in Belma green beans variety grown in an experimental plastic greenhouse. The measurements were made over a 3 week period in which up to two successive treatments with azoxystrobin and a 5 week period in which up to two successive treatments with difenoconazole were carried out. Residue levels of dicofol and difenoconazole were determined by Gas chromatography with electron capture detection (GC-ECD), liquid-liquid extraction (LLE), solid phase extraction (SPE) and high-performance liquid chromatography (HPLC). During the study, residue levels in the plantation ranged between 0.35 and 0.01 mg/kg for azoxystrobin and between 0.25 and 0.01 mg/kg for difenoconazole. The residual concentrations after the preharvest intervals (PHI) were below the legal limits

Comparative study of inhibitory efficacy of methionine and its derivatives in acidic medium by mild steel

Corrosion inhibition effect of L-Methionine (MT1), L-Methionine sulfoxide (MT2) and L-Methionine sulfone (MT3) on mild steel corrosion in 1M HCl solution was studied by using weight loss, electrochemical polarization and electrochemical impedance spectroscopy (EIS) techniques. The experimental results showed that the inhibitory efficiency of the three aminoacids improves with the increase of concentration to reach the maximum value of 95.20% for MT1, 94.14% for MT2 and 88.92% for MT3 for a concentration of 10-3M, which translates that the surface covered by the inhibitor increases with the concentration. The effect of temperature on the corrosion rate was investigated and some thermodynamic parameters were calculated. Polarization studies show that three studied inhibitors suggested that three inhibitors control the anodic as well as cathodic reactions and act as mixed type in nature. The results show that MT1, MT2 and MT3 are good inhibitors, and the adsorption of each inhibitor on mild steel surface obeys Flory-Huggins and Langmuir, with a better fit of the Langmuir isotherm through mixed adsorption (physisorption as well as chemisorption) process. In addition, the quantum approach based on density functional theory (DFT), monte Carlo (MC) and molecular dynamics (MD) simulations was confirmed the reactivity of the studied compound towards the corrosion process

Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat

Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs-VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke

Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: an update

Interleukin-1 receptor antagonist (IL-1 RA) is an anti-inflammatory protein used clinically to treat rheumatoid arthritis and is considered a promising candidate therapy for stroke. Here, we sought to update the existing systematic review and meta-analysis of IL-1 RA in models of ischaemic stroke, published in 2009, to assess efficacy, the range of circumstances in which efficacy has been tested and whether the data appear to be confounded due to reported study quality and publication bias. We included 25 sources of data, 11 of which were additional to the original review. Overall, IL-1 RA reduced infarct volume by 36.2 % (95 % confidence interval 31.6–40.7, n = 76 comparisons from 1283 animals). Assessments for publication bias suggest 30 theoretically missing studies which reduce efficacy to 21.9 % (17.3–26.4). Efficacy was higher where IL-1 RA was administered directly into the ventricles rather than peripherally, and studies not reporting allocation concealment during the induction of ischaemia reported larger treatment effects. The preclinical data supporting IL-1 RA as a candidate therapy for ischaemic stroke have improved. The reporting of measures to reduce the risk of bias has improved substantially in this update, and studies now include the use of animals with relevant co-morbidities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12975-016-0489-z) contains supplementary material, which is available to authorized users

Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization

Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century