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- Lawlor, B., et al.
(author)
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NILVAD protocol: A European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease
- 2014
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In: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 4:10
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Journal article (peer-reviewed)abstract
- Introduction: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis: Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDSADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADASCog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDRsb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDRsb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination: The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peerreviewed journal. Trial registration number EUDRACT Reference Number: 201200276427.
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- Alam, Rauful, et al.
(author)
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Selective Formation of Adjacent Stereocenters by Allylboration of Ketones under Mild Neutral Conditions
- 2013
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In: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 15:10, s. 2546-2549
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Journal article (peer-reviewed)abstract
- Allylboronic acids readily react with a broad variety of ketones, affording homoallylic alcohols with adjacent quaternary and tertiary stereocenters. The reaction proceeds with very high anti stereoselectivity even if the substituents of the keto group have a similar size. a-Keto acids react with syn stereoselectivity probably due to the formation of acyl boronate intermediates. The allylation reactions proceed without added acids/bases under mild conditions. Because of this, many functionalities are tolerated even with in situ generated allylboronic acids.
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- Alam, Rauful, et al.
(author)
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Stereoselective allylboration of imines and indoles under mild conditions. An in situ E/Z isomerization of imines by allylboroxines
- 2014
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 5:7, s. 2732-2738
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Journal article (peer-reviewed)abstract
- Direct allylboration of various acyclic and cyclic aldimine, ketimine and indole substrates was performed using allylboronic acids. The reaction proceeds with very high anti-stereoselectivity for both E and Z imines. The allylboroxines formed by dehydration of allylboronic acids have a dual effect: promoting E/Z isomerization of aldimines and triggering the allylation by efficient electron withdrawal from the imine substrate.
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- Alam, Rauful, et al.
(author)
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Stereoselective intermolecular allylic C-H trifluoroacetoxylation of functionalized alkenes
- 2012
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:21, s. 8778-8781
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Journal article (peer-reviewed)abstract
- Pd-catalyzed allylic C-H trifluoroacetoxylation of substituted alkenes was performed using PhI(OCOCF3)(2) as the oxidant and acyloxy source. Trifluoroacetoxylation of monosubstituted cyclopentenes and cyclohexenes proceeds with excellent regio- and diastereoselectivity. Studies with one of the possible (eta(3)-allyl)Pd(II) intermediates suggest that the reaction proceeds via stereoselective formation of Pd(IV) intermediates and subsequent stereo- and regioselective reductive elimination of the product.
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- Das, Arindam, et al.
(author)
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Stereocontrol in Synthesis of Homoallylic Amines. Syn Selective Direct Allylation of Hydrazones with Allylboronic Acids
- 2014
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In: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 16:14, s. 3808-3811
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Journal article (peer-reviewed)abstract
- Allylboronic acids directly react with acyl hydrazones, affording homoallylic amine derivatives. The reaction proceeds with very high syn selectivity, which is the opposite of the stereochemistry observed for allylboration of imines. The reaction can be carried out with both aromatic and aliphatic acyl hydrazones. Based on our studies the excellent syn stereochemistry can be explained by chelation control of the acyl hydrazone and the B(OH)(2) moiety.
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- Ekbom, K, et al.
(author)
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Effects of midazolam and nitrous oxide on endocrine and metabolic measurements in children
- 2012
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In: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 77:5, s. 309-319
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Journal article (peer-reviewed)abstract
- <b><i>Objective:</i></b> Pain, stress as well as drugs may affect metabolic and endocrine measurements, especially in stressed children. The aim was to study how release of glucose and stress hormones are affected when procedural sedation with nitrous oxide or midazolam are used for establishing intravenous access in obese and lean children. <b><i>Methods:</i></b> In a prospective, double-blind, randomized study 90 children, 60 obese and 30 growth-retarded (GR), aged 5–18 years, with reported anxiety or difficulties connected with i.v. access, were randomized to 1 of 3 groups: oral midazolam (0.3 mg/kg, max. 15 mg), 50% nitrous oxide (N<sub>2</sub>O), and 10% N<sub>2</sub>O. In addition, all children received anesthesia cream (EMLA®) locally 1 h before i.v. access. Blood samples were drawn at 4 time points during 30 min after establishing venous access and, when feasible, after 24 h. The 24-hour sample was regarded as obtained during unstressed condition. The effect of procedural sedation was analyzed. Children’s evaluations of pain (Numeric Rating Scale) and procedure (Likert Scale) were correlated with mean values of cortisol and glucose after i.v. access. For the metabolic and hormone control measurements, 60 children aged 4–18 years (40 obese and 20 GR) served as controls. These children underwent a 24-hour blood sampling and did not receive sedation. The control samples were drawn 10–12 h after i.v. access. <b><i>Results:</i></b> After midazolam, significantly lower cortisol levels were found compared to both 50% N<sub>2</sub>O and 10% N<sub>2</sub>O and to unstressed controls. The growth hormone levels decreased with time in the midazolam group compared to 50 and 10% N<sub>2</sub>O, where the effect of time was reversed. Glucose levels among GR children increased from 0 to 30 min, whereas the opposite was found in obese children regardless of treatment. A post hoc analysis demonstrated significant correlations between children’s evaluations of the procedure and mean values of cortisol (r = –0.53), growth hormone (r = –0.52), and norepinephrine (r = –0.5) in children treated with a very low dose of N<sub>2</sub>O (10%). <b><i>Conclusions: </i></b>When sedation is insufficient during i.v. access, and blood sampling pain and stress affect hormone values, treatment with N<sub>2</sub>O or midazolam influence the glucose and stress hormone levels differently. These differences need to be accounted for when results are used for diagnosis and clinical decisions.
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