522 research outputs found
Cocaine self-administration in the mouse: A low-cost, chronic catheter preparation
Intravenous drug self-administration is the most valid animal model of human addiction because it allows volitional titration of the drug in the blood based on an individual’s motivational state together with the pharmacokinetic properties of the drug. Here we describe a reliable low-cost mouse self-administration catheter assembly and protocol that that can be used to assess a variety of drugs of abuse with a variety of protocols. We describe a method for intravenous catheter fabrication that allows for efficient and long-lasting intravenous drug delivery. The intravenous catheters remained intact and patent for several weeks allowing us to establish stable maintenance of cocaine acquisition. This was followed by a dose response study in the same mice. For collaborators interested in premade catheters for research please make a request at www.neuro-cloud.net/nature-precedings/pomerenze
High fidelity optogenetic control of individual prefrontal cortical pyramidal neurons in vivo
Precise spatial and temporal manipulation of neural activity in specific
genetically defined cell populations is now possible with the advent of
optogenetics. The emerging field of optogenetics consists of a set of
naturally-occurring and engineered light-sensitive membrane proteins that are
able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g.,
halorhodopsin, NpHR) neural activity. Here we demonstrate the technique and the
feasibility of using novel adeno-associated viral (AAV) tools to activate
(AAV-CaMKll{\alpha}-ChR2-eYFP) or silence (AAV-CaMKll{\alpha}-eNpHR3.0-eYFP)
neural activity of rat prefrontal cortical prelimbic (PL) pyramidal neurons in
vivo. In vivo single unit extracellular recording of ChR2-transduced pyramidal
neurons showed that delivery of brief (10 ms) blue (473 nm) light-pulse trains
up to 20 Hz via a custom fiber optic-coupled recording electrode (optrode)
induced spiking with high fidelity at 20 Hz for the duration of recording (up
to two hours in some cases). To silence spontaneously active neurons we
transduced them with the NpHR construct and administered continuous green (532
nm) light to completely inhibit action potential activity for up to 10 seconds
with 100% fidelity in most cases. These versatile photosensitive tools combined
with optrode recording methods provide experimental control over activity of
genetically defined neurons and can be used to investigate the functional
relationship between neural activity and complex cognitive behavior.Comment: 4 pages, 4 figures F1000Research articl
Cocaine self-administration in the mouse: A low- cost, chronic catheter preparation
Intravenous drug self-administration is the most valid animal model of human addiction because it allows volitional titration of the drug in the blood based on an individual’s motivational state together with the pharmacokinetic properties of the drug. Here we describe a reliable low-cost mouse self-administration catheter assembly and protocol that that can be used to assess a variety of drugs of abuse with a variety of protocols. We describe a method for intravenous catheter fabrication that allows for efficient and long-lasting intravenous drug delivery. The intravenous catheters remained intact and patent for several weeks allowing us to establish stable maintenance of cocaine acquisition. This was followed by a dose response study in the same mice. For collaborators interested in premade catheters for research please make a request at www.neuro-cloud.net/nature-precedings/pomerenze
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Novel measurements of refractive index, density and mid-infrared integrated band strengths for solid O2, N2O and NO2: N2O4 mixtures
We present novel measurements of the refractive index, density and integrated band strengths of mid-infrared features of solid N2O at 16 K and of NO2 and N2O4 in two frozen NO2: N2O4 mixtures deposited at 16 and 60 K. The refractive index and density measurements were performed also for frozen O2 deposited at 16 K. In this case, the integrated band strength values could not be determined since O2 is a homonuclear molecule and therefore its fundamental mode is not infrared active. The solid samples were analysed by infrared spectroscopy in the 8000÷800 cm-1 range. The sample thickness was measured by the interference curve obtained using a He-Ne laser operating at 543 nm. The refractive index at this laser wavelength was obtained, by numerical methods, from the measured amplitude of the interference curve. The density values were obtained using the Lorentz-Lorenz relation. Integrated band strength values were then obtained by a linear fit of the integrated band intensities plotted versus column density values. The astrophysical relevance of these novel measurements is briefly discusse
Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain
The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations
Mild N-Alkylation of Amines with Alcohols Catalyzed by Acetate Ruthenium Complexes
The formation of C-N bonds for the preparation of amines compounds is a reaction of high
relevance for the synthesis of bulk and fine chemicals (1). The preparation of several drug
molecules involves N-substitution transformations that are usually performed by reaction of
amines with alkylating agents or via reductive amination. In this context, the catalytic Nalkylation
of amines using environmentally friendly alcohols as alkylating reagents and
affording water as only byproduct, is an attractive atom-economic way for the C-N bond
formation (2,3).
We report here the straightforward synthesis of the carboxylate ruthenium complexes
of formula Ru(OAc)2(diphosphane)(CO)n (n = 0, 1). These compounds are efficient catalysts
for the N-alkylation of amines using primary alcohols under mild reaction conditions, with an
alcohol / amine molar ratio of 10-100. Evidence has been provided that in catalysis a
monohydride species is formed through an equilibrium reaction
Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy
NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity
Expanded Vandermonde powers and sum rules for the two-dimensional one-component plasma
The two-dimensional one-component plasma (2dOCP) is a system of mobile
particles of the same charge on a surface with a neutralising background.
The Boltzmann factor of the 2dOCP at temperature can be expressed as a
Vandermonde determinant to the power . Recent advances in
the theory of symmetric and anti-symmetric Jack polymonials provide an
efficient way to expand this power of the Vandermonde in their monomial basis,
allowing the computation of several thermodynamic and structural properties of
the 2dOCP for values up to 14 and equal to 4, 6 and 8. In this
work, we explore two applications of this formalism to study the moments of the
pair correlation function of the 2dOCP on a sphere, and the distribution of
radial linear statistics of the 2dOCP in the plane
Avaliação dos impactos econômico, social e ambiental do uso da alfafa em sistemas de produção de leite.
Foram avaliados os impactos econômico, social e ambiental do uso da alfafa na produção de leite. Compararam-se dois sistemas de produção: a) confinamento com fornecimento de silagem de milho (seca) e pastejo rotacionado de forrageira tropical (chuvas); b) pastejo rotacionado de alfafa e suplementação com silagem de milho (seca), e pastejo rotacionado de alfafa e de forrageira tropical (chuvas). Utilizou-se a metodologia do sistema Ambitec, composto por indicadores sociais e ambientais agrupados em planilhas eletrônicas. Na análise econômica calculou-se o custo operacional efetivo (COE), do custo operacional total (COT), do custo total de produção (CT) e do lucro operacional (LO). Utilizou-se a análise de probabilidade para avaliar o risco econômico da adoção da tecnologia, por meio de uma função de lucro operacional. Os coeficientes técnicos utilizados foram fornecidos por pesquisadores da Embrapa Pecuária Sudeste, com dados da unidade de demonstração da tecnologia, e por técnicos extensionistas e produtores rurais, com dados de propriedades dos Estados do PR e de SP. A tecnologia teve índice de 1,76 para o impacto social e índice de 0,43 para o impacto ambiental. O uso da alfafa reduziu em 40% o consumo de silagem de milho na estação seca e possibilitou a redução de 8% no teor de proteína bruta do concentrado, sem prejuízo da produção média das vacas em lactação (25 L/vaca.dia em ambos os sistemas). A introdução da alfafa na dieta (20% do consumo de matéria seca) reduziu em 9% e 7% o COE e o COT de produção de leite, respectivamente. Na análise de risco, o sistema sem alfafa teve LO de R/L 0,26)
The A.P.P.A.® Project: formulation, stability and quality study of a pediatric galenic preparation for the treatment of sickle cell disease at Saint Damien hospital in Haiti.
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