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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) srt2:(2000-2009);srt2:(2007)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) > (2000-2009) > (2007)

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  • Birnir, Bryndis, et al. (författare)
  • The impact of sub-cellular location and intracellular neuronal proteins on properties of GABA(A) receptors
  • 2007
  • Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers. - 1381-6128 .- 1873-4286. ; 13:31, s. 3169-3177
  • Tidskriftsartikel (refereegranskat)abstract
    • Most studies of GABA(A) receptor accessory proteins have focused on trafficking, clustering and phosphorylation state of the channel-forming subunits and as a result a number of proteins and mechanisms have been identified that can influence the GABA(A) channel expression and function in the cell plasma membrane. In the light of a growing list of intracellular and transmembrane neuronal proteins shown to affect the fate, function and pharmacology of the GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A) receptor complex may need to be re-examined. It is perhaps more appropriate to consider the associated proteins or some of them to be parts of the receptor channel complex in the capacity of ancillary proteins. Here we highlight some of the effects the intracellular environment has on the GABA-activated channel function and pharmacology. The studies demonstrate the need for co-expression of accessory proteins with the GABA(A) channel-forming subunits in heterologous expression systems in order to obtain the full repertoire of GABA(A) receptors characteristics recorded in the native neuronal environment. Further studies e.g. on gene-modified animal models are needed for most of the accessory proteins to establish their significance in normal physiology and in pathophysiology of neurological and psychiatric diseases. The challenge remains to elucidate the effects that the accessory proteins and processes (e.g. phosphorylation) plus the sub-cellular location have on the "fine-tuning" of the functional and pharmacological properties of the GABA(A) receptor channels.
  • Krigsman, Kristin, et al. (författare)
  • Refill non-adherence to repeat prescriptions leads to treatment gaps or to high extra costs.
  • 2007
  • Ingår i: Pharmacy World & Science. - : Springer Netherlands. - 0928-1231 .- 1573-739X. ; 29:1, s. 19-24
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients. METHODS: This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed. RESULTS: The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non-exempt patients. CONCLUSION: Both undersupply and oversupply of prescribed medicines are common in Sweden. Patients with a refill adherence below 80% seem to have less than half of the prescribed treatment available. Oversupply or drug stockpiling occurs more frequently among exempt than among non-exempt patients, and this oversupply leads to high unnecessary costs.
  • Abu-Bakar, A'edah, et al. (författare)
  • Regulation of CYP2A5 gene by the transcription factor nuclear factor (erythroid-derived 2)-like 2
  • 2007
  • Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 35:5, s. 787-794
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that cadmium, a metal that alters cellular redox status, induces CYP2A5 expression in nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2(-/-)) mice but not in the knockout (Nrf2(-/-)) mice. In the present studies, the potential role of Nrf2 in cadmium-mediated regulation of Cyp2a5 gene was investigated in mouse primary hepatocytes. Cadmium chloride (CdCl2) caused a time-dependent induction of the CYP2A5 at mRNA, protein, and activity levels, with a substantial increase observed within 3 h of exposure. Immunoblotting showed cadmium-dependent nuclear accumulation of Nrf2 within 1 h of exposure. Cotransfection of mouse primary hepatocytes with Cyp2a5 promoter-luciferase reporter plasmids and Nrf2 expression plasmid resulted in a 3-fold activation of Cyp2a5 promoter-mediated transcription relative to the control. Deletion analysis of the promoter localized the Nrf2 responsive region to an area from -2656 to -2339 base pair. Computer-based sequence analysis identified two putative stress response elements (StRE) within the region at positions -2514 to -2505 and -2386 to -2377. Chromatin immunoprecipitation and electrophoretic mobility shift assays showed that interaction of the more proximal StRE with Nrf2 was stimulated by CdCl2. Finally, site-directed mutagenesis of the proximal StRE in Cyp2a5 promoter-luciferase reporter plasmids abolished Nrf2 mediated induction. Collectively, the results indicate that Nrf2 activates Cyp2a5 transcription by directly binding to the StRE in the 5'-flanking region of the gene. This acknowledges Cyp2a5 as the first phase I xenobiotic-metabolizing gene identified under the control of the StRE-Nrf2 pathway with a potential role in adaptive response to cellular stress.
  • Adane, M., et al. (författare)
  • The use of extragranular disintegrants in multiple-unit tablet formulations : effect on compressibility, compactibility and disintegration
  • 2007
  • Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 279-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.
  • Andaloussi, Mounir, et al. (författare)
  • A convenient synthesis of linear pyridinoimidazo[1,2-a] pyridine and pyrroloimidazo[1,2-a] pyridine cores
  • 2007
  • Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1359-8562. ; 48:47, s. 8392-8395
  • Tidskriftsartikel (refereegranskat)abstract
    • Two new imidazo[1,2-a] pyridine derivatives, pyridinoimidazo[1,2-a] pyridine (10) and pyrroloimidazo[1,2-a] pyridine (16), were synthesised from 2-amino-4-methyl-5-nitropyridine (1) by linear cyclisation, making use of dimethylformamide dimethylacetal (DMFDMA) as an agent of vinylamine functionalisation. This report describes first the formation of pyridine and pyrroloimidazopyridine from (1), and then the formation of pyridine-fused and pyrrolo-fused pyridine by the Friedlander method and reductive cyclisation followed by treatment of the resulting adduct with chloroacetaldehyde.
  • Andersson, Maria A., et al. (författare)
  • Evaluation of the potential genotoxicity of chromium picolinate in mammalian cells in vivo and in vitro
  • 2007
  • Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 45:7, s. 1097-1106
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromium picolinate (CrPic) is a synthetic nutritional supplement primarily used for weight loss and muscle building. Recent studies have indicated that CrPic might be genotoxic and these findings together with the wide-spread consumer use, have increased the concern about its safety. In the present study we investigated the potential genotoxicity of CrPic in mice given a single intraperitoneal injection (up to 3 mg/kg b.wt.) by evaluating the frequency of micronucleated polychromatic erythrocytes (fMNPCE) in peripheral blood, and DNA damage in lymphocytes and hepatocytes. The fMNPCE was evaluated after 42 h and DNA damage after 16 h. Using the Comet assay DNA damage was also monitored in extended-term cultures of human lymphocytes and in L5178Y mouse lymphoma cells that had been exposed for 3 h to 500 μM CrPic under different exposure conditions.A slight, but significant CrPic-induced increase in DNA damage (P < 0.001) was observed in the human lymphocytes, but only when these cells were exposed in the absence of serum. In all other experiments CrPic was found to be without genotoxic effects, both in vivo and in vitro. Taken together, our results suggest that a high concentration of CrPic might be DNA damaging, but only under non-physiological conditions.
  • Andersson, Maria, et al. (författare)
  • Evaluation of catechol-induced DNA damage in human lymphocytes : A comparison between freshly isolated lymphocytes and T-lymphocytes from extended-term cultures
  • 2007
  • Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 21:4, s. 716-722
  • Tidskriftsartikel (refereegranskat)abstract
    • Extended-term cultures of proliferating human T-lymphocytes (ETC) may be a practical alternative to freshly isolated non-proliferating peripheral blood lymphocytes (PBL) when studying genotoxicity in vitro. To investigate if the pattern of DNA damage differs between the two in vitro systems, catechol-induced DNA damage was evaluated in PBL and ETC derived from the same blood sample, using three different donors. DNA damage was monitored using the comet assay. Whereas 3 h of exposure to 0.5 mM catechol was found to be without DNA damaging effects, 3 mM was found to induce significant damage both in the PBL and the ETC (the latter being clearly less sensitive). The level of reactive oxygen species (ROS) was also measured in the ETC using the fluorescent probe carboxy-H2DCFA. ROS was found to be considerably increased both at 0.5 and 3 mM catechol. The demonstrated difference in sensitivity towards catechol-induced DNA damage between PBL and ETC may be due to their different proliferative status, but despite this difference both in vitro systems were able to identify catechol as a DNA damaging agent at the same concentration.
  • Andersson, Maria, et al. (författare)
  • Interindividual differences in initial DNA repair capacity when evaluating H2O2-induced DNA damage in extended-term cultures of human lymphocytes using the comet assay
  • 2007
  • Ingår i: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 23:6, s. 401-411
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that extended-term cultures of human lymphocytes could be used as a complement to cell lines based on transformed cells when testing the genotoxicity of chemicals. To investigate whether the pattern of induced DNA damage and its subsequent repair differs significantly between cultures based on different blood donors, hydrogen peroxide (H2O2)-induced DNA damage was measured in cultures from four different subjects using the comet assay. The DNA damage was significantly increased in all cultures after 10 min exposure to 0.25 mmol/L H2O2, and there was a significant decrease in the H2O2-induced DNA damage in all cultures after 30 min of DNA repair. The level of damage varied between the different donors, especially after the repair. Using PCR and DNA sequencing, exon 5 of the p53 gene was sequenced in the lymphocytes from the donors with the lowest and highest residual damage. No such mutation was found. Mouse lymphoma L5178Y cells carrying the p53 mutation in exon 5 were included as a reference. These cells were found to be less sensitive toward the H2O2-induced DNA damage, and they were also found to have a rather low DNA repair capacity. The demonstrated variation in H2O2-induced DNA damage and DNA repair capacity between the cultures from the different subjects may be important from a risk assessment perspective, but is obviously not of decisive importance when it comes to the development of a routine assay for genotoxicity.
  • Appukkuttan, Prasad, et al. (författare)
  • Microwave-assisted transition-metal-catalyzed synthesis of N-shifted and ring-expanded buflavine analogues
  • 2007
  • Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 13:22, s. 6452-6460
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Two novel and efficient strategies for the synthesis of hitherto unknown N-shifted and ring-expanded buflavine analogues are presented. Construction of the medium-sized ring system of the title molecules, a difficult task due to the high activation energy needed for the ring-closure with the additional rigidity imposed by the biaryl skeleton, was achieved by using Suzuki-Miyaura biaryl coupling and a ring-closing metathesis reaction as the key steps. The combination of a second-generation Grubbs catalyst and microwave irradiation proved to be highly useful in generating the otherwise difficult to obtain medium-sized ring system of the buflavine analogues.
  • Arewang, Carl Johan, et al. (författare)
  • Synthesis of urine drug metabolites : glucuronic acid glycosides of phenol intermediates
  • 2007
  • Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 342:7, s. 970-974
  • Tidskriftsartikel (refereegranskat)abstract
    • The investigation of drug metabolism requires substantial amount of metabolites. Isolation from urine is tedious, therefore, the material obtained by synthesis is preferred. Substantial amounts of three tentative drug metabolites, phenolic glucuronides, have been prepared using easily available glycosyl donors. The final products [3(2-N-methyl-N-isopropylaminoethoxy)phenyl] beta-D-glucopyranosiduronic acid, 4-amino-3,5-dimethylphenyl beta-D-glucopyranosiduronic acid and [2(S)-propanoyl-6-O-naphthyl] beta-D-glucopyranuronic acid are useful as, for example, reference material in metabolite investigations.
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