Lundstedt T.,AcurePharma AB |
Hedenstrom M.,Umeå University |
Soeria-Atmadja D.,National Food Administration |
Hammerling U.,National Food Administration |
And 3 more authors.
Chemometrics and Intelligent Laboratory Systems | Year: 2010
Functional foods are foods or dietary ingredients that provide a health benefit beyond basic nutrition. A new legislation, known as the Nutrition and Health Claims Regulation, defines the legal framework for such claims within the European Union. Any claim about the nutritional or physiological effects of a product must be scientifically demonstrated. In this study, we have focused on the exploration of metabonomics as a complementary profiling technology to establish monitoring/data analysis procedures of randomized nutritional trials. More specifically, a combined intake of soybean and grapefruit in a human intervention study was analyzed with respect to both pharmacological and physiological effects. Resulting multivariate models showed a diet-induced decrease of lactate, cholesterols and triglycerides. The most drastically elevated metabolite, myo-inositol, was found to accompany a marked reduction of triglyceride levels. Suggestively, this is due to the biotransformation of myo-inositol to phosphatidylinositol, which results in a decrease of available precursors to form triglycerides. Strong inter-subject variation was present that required special attention. Dynamic modelling of collected time series data that provided the opportunity to identify slow, medium or fast responders as well as groups of subjects showing different response profiles, was also highlighted in the study. The applied strategy of time series data has proven to be a powerful complement to randomized nutritional studies adopting a clinical trial design. © 2010 Elsevier B.V.
Tian Z.R.,University of Arkansas |
Sharma A.,Uppsala University |
Nozari A.,Massachusetts General Hospital |
Subramaniam R.,University of Arkansas |
And 3 more authors.
CNS and Neurological Disorders - Drug Targets | Year: 2012
Spinal cord injury (SCI) is a serious clinical situation for which no suitable drug therapy exists. SCI often results in paraplegia or quadriplegia and, apart from the personal trauma leads to huge costs to society for rehabilitation or day-to-day life support. Sensory motor dysfunction following SCI is mainly a consequence of the slowly progressing cord pathology after primary injury that worsens over tine. Thus, almost all sensory and motor nerve control and pathways passing through spinal cord and reflexes are compromised in SCI patients. As a result their peripheral nervous system, autonomic nervous function and central nervous system regulations are adversely affected. Experiments carried out in our laboratory show that various therapeutic agents, if given within 10 to 30 minutes after primary SCI could correct morphological changes to a certain extent. In these rat models of SCI reduction in cord pathology, e.g., bloodspinal cord barrier (BSCB) breakdown, edema formation and cell injury by the neuroprotective agents that also limited sensory motor dysfunction and improved functional behavior. However, these drugs if given beyond 30 minutes after SCI showed a markedly reduced neuroprotective efficacy. Thus, new strategies are needed to enhance neuroprotection in SCI to prevent structural and functional changes over longer periods of time. To that end our laboratory has initiated a series of investigations in which nanowired delivery of various neurotherapeutic agents are applied after different time periods of SCI, that resulted in a much better outcome than with the parent compounds under identical conditions. The superior neuroprotective activity of nanowired compound delivery could be due to a reduced metabolism of active compounds in the central nervous system (CNS) or by sustained release of the drug for longer times. In addition, nanowired drugs may penetrate the CNS faster and could reach widespread areas once entering the spinal cord. Thus, nanowired drug delivery to treat SCI may have potential therapeutic value. These aspects of nanowired drug delivery to enhance neuroprotection in SCI are discussed in this review based on our own investigations. © 2012 Bentham Science Publishers.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 16.16M | Year: 2013
Recently intense research identified around 4,000 single nucleotide polymorphisms (SNPs) associated with human age related diseases such as metabolic disorders. Despite their highly significant association to pathology, the functional role of these genetic variants is, in most cases, yet to be elucidated. The evolutionary distance of most animal models from humans represents a major limitation for the functional validation of these SNPs. To overcome these difficulties, HUMAN will generate mouse models carrying human hepatocytes or pancreatic cells from either primary cells (hepatocytes) or induced pluripotent stem cells (iPSCs). This innovative approach offers the unique possibility of studying function of genetic risk variants associated with metabolic diseases in an integrated living system (the mouse body), but within human-derived organs, i.e. liver and pancreas. iPSCs used to generate hepatocytes and cells will derive from extreme phenotypes, i.e. patients affected by severe metabolic diseases such as type 2 diabetes (T2D) or subjects selected for exceptional healthy longevity (subjects over 105 years and offspring of nonagenarian sibships) all fully clinically and metabolically characterised and genotyped; they will be selected according to the best combination of risk and protective alleles. We will test the effect of different nutritional regimes (e.g. high fat diet, caloric restriction), to disentangle the complex molecular mechanisms and circuitry across organs (e.g. hypothalamus-liver axis) which lead to pathology. HUMAN associates a core of outstanding basic research institutions to leading European biotech SMEs, and has the capability to produce at least 500 humanised mice. HUMAN will generate iPSCs biobanks and comprehensively manage all associated information. HUMAN is uniquely situated to drive innovation towards a better knowledge of the genetic basis of human metabolic diseases, thereby contributing to healthier aging of European citizens.
Akesson L.,Lund University |
Trygg J.,Umeå University |
Fuller J.M.,University of Washington |
Madsen R.,Umeå University |
And 10 more authors.
Metabolomics | Year: 2011
The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes. © 2011 Springer Science+Business Media, LLC.
Aksjonova K.,Latvian Institute of Organic Synthesis |
Belyakov S.,Latvian Institute of Organic Synthesis |
Liepinsh E.,Latvian Institute of Organic Synthesis |
Boman A.,AcurePharma AB |
And 3 more authors.
Synthesis (Germany) | Year: 2012
2-Substituted 3-chlorobenzaldehydes were prepared from the corresponding 2-(3-chlorophenyl)-1,3-dioxolanes using an ortho-lithiation strategy. The 6-chloro-2-formylbenzamide exists only in a ring form, but 6-chloro-2- formylbenzoic acid esters were isolated in both forms as open chain and cyclic tautomers. 7-Chloro-3-hydroxy-3H-isobenzofuran-1-one reacted with nucleophilic reagents at the carbonyl or quaternary carbon depending on the character of nucleophile. © Georg Thieme Verlag Stuttgart New York.
Acure Pharma Ab | Date: 2010-09-28
The present invention relates to the use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: wherein X is H or OH; R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and the pharmacologically active salts thereof.