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Novel neurotrophic factors MANF and CDNF protect neurons in primary culture
S34
e u r o p e a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 3 4 S ( 2 0 0 8 ) S30–S41
which is assumed to reflect the metabolism of neurotransmitters in brain, dopamine glucuronides have been found (Wang et al., 1983). Glucuronidation is catalysed by uridine diphosphate glucuronosyltransferases (UGTs) and isoform UGT1A6 has been found in brain but glucuronidation of dopamine has not been observed with brain microsomes thus far. In this study a liquid chromatography tandem mass spectrometric methods for the analysis of intact dopamine glucuronide was developed. For the first time dopamine glucuronide was detected in microdialysis samples collected from the rat or mouse brain. The molar ratio of dopamine and its glucuronide was about one.
Reference
Wang, P.-C., et al., 1983. J. Neurochem. 40, 1435.
The aim of the study was the evaluation of hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a carrier for piroxicam microspheres. Two types of HPMCAS were used: LF and HF. For each carrier type four formulations of piroxicam:HPMCAS were prepared by spray-drying method with different drug/carrier ratios: (1:1); (1:2); (1:3); (1:5). The properties of formulations were investigated by DSC, X-ray and scanning electron microscopy. Piroxicam dissolution profiles were studied using flow-through cell technique. Spherical shapes and smooth surfaces were found for microparticles piroxicam:HPMCAS (1:1) and (1:2). The dissolution profile of piroxicam depended on the type and amount of HPMCAS. The best results were obtained in the case of microspheres (1:5). After 15 min the amount of piroxicam dissolved from microspheres was 22 times greater then the drug alone. The characterization of samples by DSC and X-ray analysis confirmed the amorphous state of piroxicam in miscospheres. doi:10.1016/j.ejps.2008.02.093
doi:10.1016/j.ejps.2008.02.091
P17
P15
Analysis of selective androgen receptor modulators by gas chromatography-microchip atmospheric pressure ionizationmass spectrometry
Novel neurotrophic factors MANF and CDNF protect neurons in primary culture L.L. Vilponen ∗ , M.H. Voutilainen, R.K. Tuominen
2 , V. Saarela 3 , S. Franssila 3 , M. ¨ M. Haapala 1,∗ , L. Luosujarvi Thevis 4 , T. Kotiaho 1,2 , R. Kostiainen 1
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland
1
Parkinson’s disease is a neurodegenerative disease characterized by the selective loss of dopaminergic neurons in substantia nigra. At the moment there is no treatment for Parkinson’s disease that could stop the progressive neuronal loss. Mesencephalic astrocyte-derived neurotrophic factor (MANF) and the conserved dopamine neurotrophic factor (CDNF) are recently discovered neurotrophic factors. They form a new family of conserved secreted factors with eight cysteine residues of similar spacing. Those lead to unique protein folding that is unrelated to previously identified neurotrophic factors. Hence the effects of MANF and CDNF may come across different signaling pathways and therefore they could offer new therapeutic approaches to Parkinson’s disease. The effects of MANF and CDNF were studied in rat primary mesencephalic neuron-glia cultures in vitro. MANF and CDNF enhanced the survival of dopaminergic neurons determined by tyrosinehydroxylase immunostaining. MANF and CDNF also enhanced the function of dopaminergic cells in dopamine uptake assay. doi:10.1016/j.ejps.2008.02.092 NANO- AND MICROTECHNOLOGY IN PHARMACY P16 Preparation and characterization of piroxicam – hydroxypropyl methylcellulose acetate succinate microspheres A. Czech, B. Pieszczek ∗ , R. Jachowicz Department of Pharmaceutical Technology and Biopharmaceutics, ´ Poland Faculty of Pharmacy, The Jagiellonian University, Krakow,
Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Finland 2 Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, Finland 3 Microfabrication group, Department of Micro and Nanosciences, Helsinki University of Technology, Finland 4 Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Germany Selective androgen receptor modulators (SARMs) are a class of new drugs intended for prevention and treatment of osteoporosis, sarcopenia, frailty, muscle wasting, and male contraception. SARMs have similar benefits as anabolic steroids with considerably reduced side effects. Since anabolic steroids are widely used as doping, doping control authorities consider SARMS to become a major problem in the near future. In this work three 2-quinolinone-derived SARMs and two anabolic steroids were analyzed by GC-microchip APIMS using either APCI or APPI. The use of GC with APCI and APPI is possible with our heated nebulizer microchip. Previously SARMs have only been analyzed by LC-ESI-MS, which makes GC-APCI-MS and GC-APPI-MS analysis very interesting. The compounds were analyzed both in their original form and after trimethylsilylation, which is the standard operating procedure in sports drug testing. Good chromatographic behavior was achieved and the results showed good analytical performance of the methods. doi:10.1016/j.ejps.2008.02.094
e u r o p e a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 3 4 S ( 2 0 0 8 ) S30–S41
which is assumed to reflect the metabolism of neurotransmitters in brain, dopamine glucuronides have been found (Wang et al., 1983). Glucuronidation is catalysed by uridine diphosphate glucuronosyltransferases (UGTs) and isoform UGT1A6 has been found in brain but glucuronidation of dopamine has not been observed with brain microsomes thus far. In this study a liquid chromatography tandem mass spectrometric methods for the analysis of intact dopamine glucuronide was developed. For the first time dopamine glucuronide was detected in microdialysis samples collected from the rat or mouse brain. The molar ratio of dopamine and its glucuronide was about one.
Reference
Wang, P.-C., et al., 1983. J. Neurochem. 40, 1435.
The aim of the study was the evaluation of hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a carrier for piroxicam microspheres. Two types of HPMCAS were used: LF and HF. For each carrier type four formulations of piroxicam:HPMCAS were prepared by spray-drying method with different drug/carrier ratios: (1:1); (1:2); (1:3); (1:5). The properties of formulations were investigated by DSC, X-ray and scanning electron microscopy. Piroxicam dissolution profiles were studied using flow-through cell technique. Spherical shapes and smooth surfaces were found for microparticles piroxicam:HPMCAS (1:1) and (1:2). The dissolution profile of piroxicam depended on the type and amount of HPMCAS. The best results were obtained in the case of microspheres (1:5). After 15 min the amount of piroxicam dissolved from microspheres was 22 times greater then the drug alone. The characterization of samples by DSC and X-ray analysis confirmed the amorphous state of piroxicam in miscospheres. doi:10.1016/j.ejps.2008.02.093
doi:10.1016/j.ejps.2008.02.091
P17
P15
Analysis of selective androgen receptor modulators by gas chromatography-microchip atmospheric pressure ionizationmass spectrometry
Novel neurotrophic factors MANF and CDNF protect neurons in primary culture L.L. Vilponen ∗ , M.H. Voutilainen, R.K. Tuominen
2 , V. Saarela 3 , S. Franssila 3 , M. ¨ M. Haapala 1,∗ , L. Luosujarvi Thevis 4 , T. Kotiaho 1,2 , R. Kostiainen 1
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland
1
Parkinson’s disease is a neurodegenerative disease characterized by the selective loss of dopaminergic neurons in substantia nigra. At the moment there is no treatment for Parkinson’s disease that could stop the progressive neuronal loss. Mesencephalic astrocyte-derived neurotrophic factor (MANF) and the conserved dopamine neurotrophic factor (CDNF) are recently discovered neurotrophic factors. They form a new family of conserved secreted factors with eight cysteine residues of similar spacing. Those lead to unique protein folding that is unrelated to previously identified neurotrophic factors. Hence the effects of MANF and CDNF may come across different signaling pathways and therefore they could offer new therapeutic approaches to Parkinson’s disease. The effects of MANF and CDNF were studied in rat primary mesencephalic neuron-glia cultures in vitro. MANF and CDNF enhanced the survival of dopaminergic neurons determined by tyrosinehydroxylase immunostaining. MANF and CDNF also enhanced the function of dopaminergic cells in dopamine uptake assay. doi:10.1016/j.ejps.2008.02.092 NANO- AND MICROTECHNOLOGY IN PHARMACY P16 Preparation and characterization of piroxicam – hydroxypropyl methylcellulose acetate succinate microspheres A. Czech, B. Pieszczek ∗ , R. Jachowicz Department of Pharmaceutical Technology and Biopharmaceutics, ´ Poland Faculty of Pharmacy, The Jagiellonian University, Krakow,
Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Finland 2 Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, Finland 3 Microfabrication group, Department of Micro and Nanosciences, Helsinki University of Technology, Finland 4 Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Germany Selective androgen receptor modulators (SARMs) are a class of new drugs intended for prevention and treatment of osteoporosis, sarcopenia, frailty, muscle wasting, and male contraception. SARMs have similar benefits as anabolic steroids with considerably reduced side effects. Since anabolic steroids are widely used as doping, doping control authorities consider SARMS to become a major problem in the near future. In this work three 2-quinolinone-derived SARMs and two anabolic steroids were analyzed by GC-microchip APIMS using either APCI or APPI. The use of GC with APCI and APPI is possible with our heated nebulizer microchip. Previously SARMs have only been analyzed by LC-ESI-MS, which makes GC-APCI-MS and GC-APPI-MS analysis very interesting. The compounds were analyzed both in their original form and after trimethylsilylation, which is the standard operating procedure in sports drug testing. Good chromatographic behavior was achieved and the results showed good analytical performance of the methods. doi:10.1016/j.ejps.2008.02.094