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

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

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21.
  • Nicklasson, Fredrik (författare)
  • Compression mechanics of pharmaceutical aggregates : Studies on the tabletting of spheronised aggregates with varying composition and porosity
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The thesis investigated the tabletting behaviour of aggregates of different porosity and material composition, and focused on the role of the compression mechanics of the aggregates as a link between their structure and composition and the structure and functionality of tabletsformed from them. The aggregates studied all responded to compression by deformation and densification. Furthermore, the deformation behaviour of aggregates was found to consist of three deformation characteristics: The capacity for deformation, that is the maximum amount of deformation that can occur when aggregates that are compressed in a tabletting die.The mode of deformation, that refers to the ability of aggregates in a bed to conform to the surfaces of adjacent aggregates during compression, thus minimising the intergranular pore volume. If this ability is well developed, the aggregates are said to exhibit a surface oriented mode of deformation, as opposed to a bulk oriented mode of deformation.The resistance to deformation, that is the magnitude of the shear stress during tabletting that is associated with aggregate deformation.If aggregates have a high capacity for deformation, the total densification of the tablet structure will be high. A surface oriented mode of deformation during compression will result in a dense packing of aggregates in the formed tablets. The resistance to deformation will decide the pressure range in which the greatest changes to the tabletstructure will occur. The intergranular pore structure in tablets was shown to be a controlling factor for the mechanical strength of the tablets.The thesis contributes to the mechanistic understanding of the tabletting process for aggregates as well as the methodology in the field of research in a way that may be of use for the development of the solid dosage forms of tomorrow.
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22.
  • Norlin, Maria, et al. (författare)
  • 24-Hydroxycholesterol is a substrate for hepatic cholesterol 7 alpha-hydroxylase (CYP7A)
  • 2000
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 41:10, s. 1629-1639
  • Tidskriftsartikel (refereegranskat)abstract
    • (24S)-Hydroxycholesterol is formed from cholesterol in the brain and is important for cholesterol homeostasis in this organ. Elimination of (24S)-hydroxycholesterol has been suggested to occur in the liver but little is known about the metabolism of this oxysterol. In the present investigation, we report formation of 7alpha, 24-dihydroxycholesterol in pig and human liver. 7alpha-hydroxylase activity toward both isomers of 24-hydroxycholesterol [(24S) and (24R)] was found in a partially purified and reconstituted cholesterol 7alpha-hydroxylase (CYP7A) enzyme fraction from pig liver microsomes. In contrast, a purified enzyme fraction of pig liver oxysterol 7alpha-hydroxylase with high activity toward 27-hydroxycholesterol did not show any detectable activity toward 24-hydroxycholesterol. 7alpha-Hydroxylation of 24-hydroxycholesterol was strongly inhibited by 7-oxocholesterol, a known inhibitor of CYP7A. Human CYP7A, recombinantly expressed in Escherichia coli and in simian COS cells, showed 7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol, with a preference for the (24S)-isomer. Our results show that 24-hydroxycholesterol is metabolized by CYP7A, an enzyme previously considered to be specific for cholesterol and cholestanol and not active toward oxysterols. Because CYP7A is the rate-limiting enzyme in the major pathway of bile acid biosynthesis, the possibility is discussed that at least part of the 24-hydroxycholesterol is converted into 7alpha-hydroxylated bile acids by the enzymes involved in the normal biosynthesis of bile acids.
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23.
  • Norlin, Maria (författare)
  • Cytochrome P450 Enzymes in the Metabolism of Cholesterol and Cholesterol Derivatives
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cholesterol is metabolized to a variety of important biological products in the body including bile acids and vitamin D. The present investigation is focused on enzymes that catalyze 7α-hydroxylation or 27-hydroxylation in the metabolism of cholesterol, oxysterols (side chain-hydroxylated derivatives of cholesterol) and vitamin D3. The enzymes studied belong to the cytochrome P450 enzyme families CYP7 and CYP27.The study describes purification of a cytochrome P450 enzyme fraction active in 7α-hydroxylation of 25-hydroxycholesterol, 27-hydroxycholesterol, dehydroepiandrosterone and pregnenolone from pig liver microsomes. Peptide sequence analysis indicated that this enzyme fraction contains an enzyme belonging to the CYP7B subfamily. The purified enzyme was not active towards cholesterol or testosterone. Purification and inhibition experiments suggested that hepatic microsomal 7α -hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone involves at least two enzymes, probably closely related.The study shows that recombinantly expressed human and rat cholesterol 7α -hydroxylase (CYP7A) and partially purified pig liver cholesterol 7α -hydroxylase are active towards 20(S)-, 24-, 25- and 27-hydroxycholesterol. CYP7A was previously considered specific for cholesterol and cholestanol. The 7α -hydroxylation of 20(S)-, 25-, and 27-hydroxycholesterol in rat liver was significantly increased by treatment with cholestyramine, an inducer of CYP7A. Cytochrome P450 of renal origin showed 7α -hydroxylase activity towards 25- and 27-hydroxycholesterol, dehydroepiaundrosterone and pregnenolone but not towards 20(S)-, 24-hydroxycholesterol or cholesterol. The results indicate a physiological role for CYP7A as an oxysterol 7α -hydroxylase, in addition to the previously known human oxysterol 7α -hydroxylase CYP7B.The role of renal sterol 27-hydroxylase (CYP27A) in the bioactivation of vitamin D3 was studied with cytochrome P450 fractions purified from pig kidney mitochondria. Purification and inhibition experiments and experiments with a monoclonal antibody against CYP27A indicated that CYP27A plays a role in renal 25-hydroxyvitamin D3 l α -hydroxylation.The expression of CYP7A, CYP7B and CYP27A during development was studied. The levels of CYP27A in livers of newborn and six months old pigs were similar whereas the levels of CYP7A increased. The expression of CYP7B varied depending on the tissue. The expression of CYP7B increased with age in the liver whereas the CYP7B levels in kidney showed a marked age-dependent decrease.
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24.
  • Norlin, Maria, et al. (författare)
  • Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase (CYP7A)
  • 2000
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:44, s. 34046-34053
  • Tidskriftsartikel (refereegranskat)abstract
    • A 7 alpha-hydroxylation is necessary for conversion of both cholesterol and 27-hydroxycholesterol into bile acids. According to current theories, cholesterol 7 alpha-hydroxylase (CYP7A) is responsible for the former and oxysterol 7 alpha-hydroxylase (CYP7B) for the latter reaction. CYP7A is believed to have a very high substrate specificity whereas CYP7B is active toward oxysterols, dehydroepiandrosterone, and pregnenolone. In the present study, 7 alpha-hydroxylation of various oxysterols in liver and kidney was investigated. Surprisingly, human cholesterol 7 alpha-hydroxylase, CYP7A, expressed as a recombinant in Escherichia coli and COS cells, was active toward 20(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol. This enzyme has previously been thought to be specific for cholesterol and cholestanol. A partially purified and reconstituted cholesterol 7 alpha-hydroxylase enzyme fraction from pig liver showed 7 alpha-hydroxylase activity toward the same oxysterols as metabolized by expressed recombinant human and rat CYP7A. The 7 alpha-hydroxylase activity toward 20(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol in rat liver was significantly increased by treatment with cholestyramine, an inducer of CYP7A. From the present results it may be concluded that CYP7A is able to function as an oxysterol 7 alpha-hydroxylase, in addition to the previously known human oxysterol 7 alpha-hydroxylase, CYP7B. These findings may have implications for oxysterol-mediated regulation of gene expression and for pathways of bile acid biosynthesis. A possible use of 20(S)-hydroxycholesterol as a marker substrate for CYP7A is proposed.
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25.
  • Olsson, Helena (författare)
  • Particle interactions and internal tablet structure : Factors affecting the mechanical strength of pharmaceutical compacts
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A simple tablet model was utilised to identify parameters responsible for tablet compactibility. In this model tablets were considered as homogeneous and isotropic aggregates of individual spherical particles. If the particles were located close enough to each other, interparticulate bonds were assumed to be developed. By testing the tensile strength of tablets made from mixtures of fine particulate polyethylene glycols and coarse sodium chloride or sodium bicarbonate particles it was confirmed that tablets normally fracture around the tablet particles rather than through and that interparticulate bonds are responsible for the coherency of tablets.A method of compressing tablets in media with differing dielectric constants to obtain information on dominating interparticulate bonding mechanisms was evaluated and found to be useful in distinguishing between different bond types. By applying this method it was verified that distance forces probably are the dominating interparticulate bonding mechanism in most pharmaceutical compacts. For stronger bonds (solid bridges) to occur certain prerequisites must be fulfilled such as a simple chemical structure at particle surfaces and a high interparticulate strain during compression.From the simple tablet model it was derived that tablet porosity and specific surface area have a profound effect on tablet strength. By dividing the tablet strength with a factor combining tablet porosity and specific surface area, the results concerning dominating bond types in tablets were confirmed. For some materials, a change in compression speed resulted in a change in tablettensile strength without the expected corresponding changes in tablet porosity or specific surface area. Therefore it was discussed that surface deformability, which not was directly considered in the simple tablet model, might also have a marked effect on tablet strength.The tablet model was also used to discuss the strength enhancing effect of dry binders and the effect of speed of compression on tablet tensile strength.
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26.
  • Rosén, Annika, et al. (författare)
  • Central changes in nociceptin, dynorphin and met-enkephalin-Arg-Phe in different models of nociception
  • 2000
  • Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 857:1-2, s. 212-218
  • Tidskriftsartikel (refereegranskat)abstract
    • The newly identified neuropeptide nociceptin/orphanin FQ (NOC) was measured in different rat brain areas related to the descending anti-nociceptive pathways and compared to two opioid peptides, dynorphin B (DYN B) and Met-enkephalinArgPhe (MEAP). Two experimental models of chronic nociception, one neurogenic and one inflammatory, used in this study, reveal how different pathological conditions may influence these endogenous systems. Nerve injury is induced by ligation of the sciatic nerve and inflammation by a carrageenan injection in the gluteal muscle, 2 weeks prior to decapitation. Selected brain areas were dissected out and frozen. NOC-, DYN B- and MEAP-like immunoreactivity (LI) is determined by radioimmunoassay. Nerve injury increased the NOC-LI levels in the cortex cinguli, DYN B-LI levels in the dorsal and the ventral part of the spinal cord, whereas a decrease in the MEAP-LI levels is seen in the dorsal part of the periaqueductal grey (PAG). After inflammation, the NOC-LI levels increased in cortex cinguli, hypothalamus and in the dorsal spinal cord, whereas DYN B-LI levels increased in the dorsal part of the PAG. A general increase in MEAP-LI levels is found after inflammation in all analyzed brain areas except in hippocampus. In conclusion, increased levels of NOC-LI were found in cortex cinguli in both treatment groups and in hypothalamus and spinal cord following carrageenan treatment. The changes in the NOC-LI concentrations were not parallelled by changes in DYN B-LI and MEAP-LI, suggesting that NOC and opioid peptides elicit different reactions in the systems of nociception/antinociception.
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27.
  • Sanderson Nydahl, Katarina (författare)
  • Hemorphins and endomorphins
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In this thesis, two newly discovered endogenous opioid peptide families, the hemorphins and endomorphins, are investigated with emphasis on modulation of pain and inflammation. In addition, the presence of hemorphins in human biological fluids as well as the in vitro and in vivo processing ofLVV-hemorphin-7 in blood and brain is investigated.Using various chromatographic techniques in combination with radioimmunoassay, several hemorphin-like peptides were detected in cerebrospinal fluid from patients with cerebrovascular bleedings, but only in negligible amounts in control CSF.Results from in vitro experiments in human plasma showed that LVV-hemorphin-7 was metabolized mainly from the N-terminal end, as determined by RP-HPLC and micro-electrospray mass spectromety. In vivo microdialysis was used to study the processing of LVV-hemorphin-7 in rat striatum and blood. The results demonstrated that the decapeptide was metabolized to form C-terminal fragments, consistent with the results in vitro, however an N-terminal fragment and several internal fragments were also detected.The modulatory effects of hemorphin-7 and endomorhin-1 (EM-l) on a peripheral inflammatory response were investigated in a blister model in the rat hind paw. The results showed that hemorphin-7 (20µM) and EM-1 (100µM) inhibited the vascular response to electrical stimulation of the sciatic nerve at 20V, 5Hz, 2ms by 54% and 58%, respectively. When exogenously perfused over blisters induced acutely in naive skin, both peptides were shown to attenuate both plasmaextravasation and vasodilatation responses to substance P in a naloxone-revesible manner, suggesting an involvement of opioid receptor(s) in these responses. While hemorphin-7 was shown to modulate the peripheral inflammatory response, in acute injury conditions only, EM-l was able to attenuate this response in acute, as well as recurrent and chronic injury conditions. The results presented support the proposition that different endogenous inhibitory mechanisms operate under different injury conditions.A rat model with thermal stimulation was used to compare the antinociceptive properties of intrathecally administered EM-l to morphine. I.t. injections of 100 µg of EM-1 resulted in significantly prolonged withdrawal times after 10 and 20 min, indicating an antinociceptive effect of the peptide. The results also showed that EM-l had a shorter duration and lower potency compared to morphine in this preparation.
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28.
  • Savolainen, Vincent, et al. (författare)
  • Phylogeny of the eudicots : a nearly complete familial analysis based on rbcL gene sequences
  • 2000
  • Ingår i: Kew bulletin. - 0075-5974 .- 1874-933X. ; 55:2, s. 257-309
  • Tidskriftsartikel (refereegranskat)abstract
    • A phylogenetic analysis of 589 plastid rbcL gene sequences representing nearly all eudicot families (a total of 308 families; seven photosynthetic and four parasitic families are missing) was performed, and bootstrap re-sampling was used to assess support for clades. Based on these data, the ordinal classification of eudicots is revised following the previous classification of angiosperms by the Angiosperm Phylogeny Group (APG). Putative additional orders are discussed (e.g. Dilleniales, Escalloniales, Vitales), and several additional families are assigned to orders for future updates of the APG classification. The use of rbcL alone in such a large matrix was found to be practical in discovering and providing bootstrap support for most orders. Combination of these data with other matrices for the rest of the angiosperms should provide the framework for a complete phylogeny to be used in macro-evolutionary studies.
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29.
  • Scherlund, Marie (författare)
  • In situ gelling drug delivery systems for periodontal anaesthesia
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In this thesis local anaesthetic formulations based on PEO-PPO-PEO block copolymers (PEO and PPO being poly(ethylene oxide) and poly(propylene oxide), respectively) or nonionic cellulose ethers undergoing temperature- or dilution-induced thickening were investigated. The aim of the work was to develop formulations which can be easily administered to the periodontal pocket, stay at the application site, give a fast onset of anaesthesia and have a duration sufficient to perform periodontal scaling procedures. Emulsions, (mixed) micellar solutions and microemulsions fulfilling the requirements stated above were achieved by combining the active ingredients lidocaine and prilocaine with the nonionic block copolymers Lutrol® F127 and Lutrol® F68. The critical micellisation and gelation temperatures of the systems were found to be interconnected and influenced by the total polymer concentration and the polymer mixture composition, as well as the presence of cosolutes and pH. A low-viscous isotropic phase that turns into a high-viscous hexagonal phase as the water content increases was found by combining Lutrol® F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM. The system has a slower release rate compared to the microemulsion formulation which might make it suitable for indications where a longer duration is needed. Finally, a temperature-induced gelling system was achieved by adding lidocaine and prilocaine to mixtures of ethyl(hydroxyethyl)cellulose (EHEC) and sodium dodecyl sulfate (SDS), hexadecyltrimethylammonium bromide (CTAB) or myristoylcholine bromide systems at, or just below, the surfactant concentration found to give a maximum viscosity increase at room temperature. In particular, the myristoylcholine bromide system may be interesting considering its antibacterial properties and biodegradability.
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30.
  • Segura, Laura, et al. (författare)
  • Anti-inflammatory activity of dichloromethane extract of Heterotheca inuloides in vivo and in vitro
  • 2000
  • Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 66:6, s. 553-555
  • Tidskriftsartikel (refereegranskat)abstract
    • The dichloromethane extract from the dried flowers of Heterotheca inuloides Cass. was investigated on several pharmacological models of inflammation in vivo and in vitro. It showed anti-inflammatory activity on the croton oil-induced oedema test in mouse ear, at 1 mg/ear. The compound isolated from this extract, 7-hydroxy-3,4-dihydrocadalin, showed anti-inflammatory effect on the same experimental model (ED50 of 0.9 mumol/ear), as well as on COX-1 and COX-2 catalysed prostaglandin biosynthesis assays, with IC50 values of 22 microM and 526 microM, respectively. No effect was observed on carrageenan-induced oedema and on fMLP/PAF-induced exocytosis of human neutrophils. The COX-1 inhibitory effect showed by 7-hydroxy-3,4-dihydrocadalin might be related to the anti-inflammatory activity on the topical oedema induced by croton oil.
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