N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a new cholinesterase and monoamine oxidase dual inhibitor

On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor.PostprintPostprintPeer reviewe

Medication use in pregnancy: a cross-sectional, multinational web-based study

Objectives: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. his study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants: Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of ute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than nonimmigrants. Conclusions: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used

Mean field approximation for noisy delay coupled excitable neurons

Mean field approximation of a large collection of FitzHugh-Nagumo excitable neurons with noise and all-to-all coupling with explicit time-delays, modelled by $N\gg 1$ stochastic delay-differential equations is derived. The resulting approximation contains only two deterministic delay-differential equations but provides excellent predictions concerning the stability and bifurcations of the averaged global variables of the exact large system.Comment: 15 pages, 3 figure

Mean field approximation of two coupled populations of excitable units

The analysis on stability and bifurcations in the macroscopic dynamics exhibited by the system of two coupled large populations comprised of $N$ stochastic excitable units each is performed by studying an approximate system, obtained by replacing each population with the corresponding mean-field model. In the exact system, one has the units within an ensemble communicating via the time-delayed linear couplings, whereas the inter-ensemble terms involve the nonlinear time-delayed interaction mediated by the appropriate global variables. The aim is to demonstrate that the bifurcations affecting the stability of the stationary state of the original system, governed by a set of 4N stochastic delay-differential equations for the microscopic dynamics, can accurately be reproduced by a flow containing just four deterministic delay-differential equations which describe the evolution of the mean-field based variables. In particular, the considered issues include determining the parameter domains where the stationary state is stable, the scenarios for the onset and the time-delay induced suppression of the collective mode, as well as the parameter domains admitting bistability between the equilibrium and the oscillatory state. We show how analytically tractable bifurcations occurring in the approximate model can be used to identify the characteristic mechanisms by which the stationary state is destabilized under different system configurations, like those with symmetrical or asymmetrical inter-population couplings.Comment: 5 figure

Reactive organoallyl species generated from aryl halides and allene: allylation of alpha,beta-unsaturated aldehydes and cyclic ketones employing Pd/In transmetallation processes

Allylation of α,β-unsaturated aldehydes and cyclic ketones promoted by Pd/In transmetallation processes has been studied. The unsaturated aldehydes underwent regioselective 1,2-addition to afford secondary homoally alcohols. The reactions have been performed using Pd(OAc)2/PPh3 as catalytic system and metallic indium affording the products in good yields. The same transformation with unsaturated ketones proved to be less efficient, while saturated cyclic ketones delivered generally excellent yields in the presence of CuI. In these latter processes the presence of a distal heteroatom influences the reaction rate

One-loop structure of the U(1) gauge model on the truncated Heisenberg space

We calculate divergent one-loop corrections to the propagators of the U(1) gauge theory on the truncated Heisenberg space, which is one of the extensions of the Grosse-Wulkenhaar model. The model is purely geometric, based on the Yang-Mills action; the corresponding gauge-fixed theory is BRST invariant. We quantize perturbatively and, along with the usual wave-function and mass renormalizations, we find divergent nonlocal terms of the $\Box^{-1}$ and $\Box^{-2}$ type. We discuss the meaning of these terms and possible improvements of the model.Comment: 29 page

Stereoselective synthesis of chiral β2,3-disubstituted-β-amino acid derivatives using Pd/In transmetallation cascade processes

A new, highly efficient synthesis of chiral β2,3-disubstituted-β-amino acid derivatives has been developed, based on an allylation procedure employing allene and a catalytic Pd/In bimetallic process

In silico methods in stability testing of hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network

This article presents the possibility of using of multiple regression analysis (MRA) and dynamic neural network (DNN) for prediction of stability of Hydrocortisone 100 mg (in a form of hydrocortisone sodium succinate) freeze-dried powder for injection packed into a dual chamber container. Degradation products of hydrocortisone sodium succinate: free hydrocortisone and related substances (impurities A, B, C, D and E; unspecified impurities and total impurities) were followed during stress and formal stability studies. All data obtained during stability studies were used for in silico modeling; multiple regression models and dynamic neural networks as well, in order to compare predicted and observed results. High values of coefficient of determination (0.950.99) were gained using MRA and DNN, so both methods are powerful tools for in silico stability studies, but superiority of DNN over mathematical modeling of degradation was also confirmed

Modified local diatomite as potential functional drug carrier - a model study for diclofenac sodium

Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (~373 mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8 h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8 h) and those containing physical mixture of the same composition (up to 45% after 8 h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favour the application of diatomite as a potential functional drug carrier

Self-reported perinatal depressive symptoms and postnatal symptom severity after treatment with antidepressants in pregnancy: a cross-sectional study in 12 European countries using the Edinburgh Postnatal Depression Scale

Purpose: To explore the prevalence of self-reported antenatal and postnatal depressive symptoms by severity across multiple countries and the association between antidepressant treatment in pregnancy and postnatal symptom severity. Patients and methods: Multinational web-based study in 12 European countries (n=8069). Uniform data collection was ensured via an electronic questionnaire. Pregnant women at any gestational week and mothers of children with less than one year of age, could participate. We used the Edinburgh Postnatal Depression Scale (EPDS) to measure prevalence of antenatal and postnatal depressive symptoms according to severity, which were corrected by survey-weight adjustment (descriptive analysis). Within mothers with a psychiatric disorder (n=173), we estimated the association between antidepressant treatment in pregnancy and postnatal depressive symptom severity, as standardized EPDS mean scores, via inverse probability of treatment weight (association analysis). Results: In the descriptive analysis (n=8069), the period prevalence of moderate to very severe depressive symptoms was higher in the Western and Eastern regions relative to the Northern, both in the ante- (6.8-7.5% vs 4.3%) and postnatal period (7.6% vs 4.7%). One in two mothers with psychiatric disorders used antidepressant in pregnancy (86 out of 173). In the association analysis, women medicated at any time during pregnancy (adjusted β: -0.34, 95% CI: -0.66, -0.02) had a significant postnatal symptom severity reduction compared with the nonmedicated counterpart. This effect was larger (β: -0.74, 95% CI: -1.24, -0.24) when the analysis was restricted to mothers within six months after childbirth. Conclusions: The prevalence of self-reported antenatal and postnatal depressive symptoms differs across European countries. Among women with psychiatric disorders, those who had been on treatment with antidepressants during pregnancy were less likely to report postnatal depressive symptoms, particularly within the six-month period after childbirth, compared to the nonmedicated counterpart