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

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

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

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$/L 0,26 (19,2$/L 0,26)

Infrared, UV/VIS and Raman Spectroscopy of Comet Wild-2 Samples Returned by the Stardust Mission

Results from the preliminary examination of Stardust samples obtained using various spectroscopic methods will be presented

Ion irradiation of N2O ices and NO2:N2O4 ice mixtures: first steps to understand the evolution of molecules with the N−O bond in space

Astronomical observations towards star forming regions have revealed the presence of molecules with the N-O bond such as NO, N2O, and HNO. These species are considered potential precursors of prebiotic molecules. Thus understanding nitrogen and oxygen chemistry may help us to better understand the origin and evolution of prebiotic molecules in space. However, species with the N−O bond are poorly studied and laboratory works on the effects induced on them by solar wind and galactic cosmic rays are still scarce. For this, we wanted to study the effects of ion bombardment on molecules with the N−O bond. We focus here on N2O ices and NO2:N2O4 = 1:1 ice mixtures (at 16 and 50/60 K) irradiated with 200 keV protons. Infrared transmission spectroscopy (8000−500 cm-¹; 1.25−20 μm) was used to analyze the samples. Irradiation of N2O ices and NO2:N2O4 ice mixtures produces comparable effects independent of the irradiation temperature, NO being the main product. Moreover, we show that the maximum amount of N2O and N2O4 destroyed by irradiation, at the highest dose reached in our experiments, is equal to about 98 and 70%, respectively. The dose range covered in the experiments has been compared with the astrophysical timescale of surface processing in space, showing that irradiation of N2O and NO2:N2O4 mixtures can produce, within 10⁵−10⁸ years, amounts of solid NO ice detectable towards star forming regions by the James Webb Space Telescope