Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Cancer Chemotherapy and Pharmacology - Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of...     

Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus

The thymoma prone BUF/Mna (B) rat is a useful model for Studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at al stages of life. A locus, Ten-1 , which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the bus, (B×(B×MITE)F1) BC rats were generated by crossing the B strain with the Inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargements were found In genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11 , and D1Mit6 , by X^2-test and Student's t -test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1 , in this region. Paradoxically, a suppressive locus, Tsu-1 , to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT D3Mit16 , and D3Mit13 . By analyses of mapmaker/exp and mapmaker/qtl, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.     

Application of Microalgal Physiological Response as Biomarker for Evaluating the Toxicity of the Textile Dye Alizarin Red S

Textile dyes are becoming a growing threat to the environment. This report presents the findings of the study on the toxicity of the textile dye Alizarin Red S on two freshwater microalgae. The acute toxicity assay revealed that 96-h EC₅₀ values of Chlorella vulgaris and Spirulina platensis were 29.81 mg/L and 18.94 mg/L respectively. The pigments chlorophyll-a, b and carotenoids in C. vulgaris on 96-h exposure to the dye were 2.91, 3.29 and 3.01 times lower in analogy to control whereas Spirulina platensis showed 2.89and 2.56 fold decrease in chlorophyll-a and carotenoid content than control. After the test period of 96-h with dye, the protein content of C. vulgaris and S. platensis were 2.33 and 1.77 times lower compared to the control. The growth inhibition rate, pigment as well as the protein content declined in compliance with the rise in dye concentration, which anticipate paradigm about the toxic effects of the textile dye.

     

Impact Assessment on the Aquatic Ecosystem in the Vicinity of an Operating Nuclear Power Plant at the Kalpakkam Coastal Site

An inherent problem in electricity generation is that much of the heat produced cannot be converted into electricity and is dissipated in nearby heat sinks, such as lakes, rivers and oceans. In India, such heat rejection to water bodies is governed by legislation from ministry of environment and forests and central and state pollution control boards. New standards for thermal discharge issued by MoE&F in 1998 seem to be very stringent. But in the absence of relevant data for Indian sites appear to be somewhat justified. In order to make a realistic assessment of the impact of thermal discharge on aquatic ecosystems, the Department of Atomic Energy initiated the first major thermal ecological study in the country at two of its operating nuclear power plants, one at a coastal site in Kalpakkam and the other on the banks of river Kali at Kaiga. The 5 years duration co-ordinated research project involved researchers from eight different universities and national laboratories and experts from NIO, NIOT, CECRI, BARC, NPCIL and MoE&F. In view of the fact that the most of the forthcoming nuclear power plants in the country are coastally located, this article discusses the findings of Thermal Ecological Study at Kalpakkam. A major achievement of the study was to map the precise boundaries of the small mixing zone, the region of confluence of the heated water with the recipient water body, wherein the thermal plume effected a ∆T of only 3–5 °C due to rapid inundation and mixing with turbulent sea water. This caused a limited impact on the growth and distribution of the relatively sedentary benthic flora and fauna, though none of the motile forms, including fishes, were affected. Beyond the mixing zone, the life appeared to be as near normal as possible. No change in any physico-chemical parameter was noticed, except for a small expected decrease in dissolved oxygen at the discharge point. At Kalpakkam, position of the mixing zone shifts periodically due to formation of a natural sand bar by sea currents. This allows restoration of parameters, especially temperature to more conducive values and results in recolonization of the previously impacted sites. An ecologically encouraging finding of the study was that the impact was restricted in space and reversible in time. The data generated are expected to aid regulatory agencies in formulation of more appropriate stipulations for thermal discharge and also guide power industry to design eco-friendly technologies in future.

     

Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery*

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD).

Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded.

Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD.

Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.     

Criteria for Emergency Brain MRI During Stroke-Alert

ObjectivesIntravenous (IV) tissue plasminogen activator (tPA) should be given to patients with acute ischemic stroke (AIS) and avoided in stroke mimics (SM). Select use of emergency brain magnetic resonance imaging (eMRI-brain) in stroke-alerts aids diagnosis, but accepted utilization criteria for eMRI-brain do not currently exist. We developed criteria for eMRI-brain and report the yield of eMRI-brain in stroke-alert patients.Materials and MethodsWe developed three history-based criteria for performing eMRI-brain during stroke-alerts: (1) history of previous similar deficits, (2) change in consciousness at onset of symptoms, (3) symptom presentation consistent with migraine aura. We then performed a retrospective chart review of patients who presented as a stroke-alert over a 5-year period and determined how these criteria affected administration of IV tPA to AIS and SM patients.ResultsAmong 3,512 stroke-alerts, 230 (8.1%) patients met our criteria for eMRI-brain exams: 217 (92.6%) had SM and 17 (7.4%) had AIS. Our IV tPA decision-making analysis showed that based on eMRI-brain IV tPA was less frequently administered to SM patients (PCC-0.841, p=0.036) with less failures to administer IV tPA to patients with AIS (PCC -0.907, p-value=0.013, Pearson correlation coefficient). No patients became ineligible for IV tPA due to MRI-related time delays.ConclusionsOur history based criteria for performing eMRI-brain during stroke-alerts show a high yield of stroke mimics. Selective eMRI-brain improves decision-making accuracy regarding IV tPA administration.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.