21.
Park, Ki-Ryong, et al.
(författare)
Origin of the cyathium-bearing Euphorbieae (Euphorbiaceae) : phylogenetic study based on morphological characters
2002
Ingår i: Botanical bulletin of Academia Sinica. - 0006-8063. ; 43:1, s. 57-62
Tidskriftsartikel (refereegranskat) abstract
A cladistic analysis of the subfamily Euphorbioideae was undertaken to elucidate the origin of the cyathium-bearing Euphorbieae and to provide hypotheses about evolutionary relationships within the subfamily. Twenty-one species representing most of the genera within the study group and three outgroup taxa from the subfamilies Acalyphoideae and Crotonoideae were selected for parsimony analysis. An unweighted parsimony analysis of 24 morphological characters resulted in five equally parsimonious trees with consistency indices of 0.67 and tree lengths of 39 steps. The strict consensus tree supported monophyly of the cyathium-bearing Euphorbieae. The sister group relationships of cyathium bearing Euphorbieae with Maprounea (subtribe Hippomaninae) were supported weakly, and the origin of cyathium is possibly in Hippomaneae, or in the common ancestor of Euphorbieae and remaining taxa of Euphorbioideae plus Acalyphoideae. Within the tribe Euphorbieae, both subtribes Euphorbiinae and Neoguilauminiinae are monophyletic, but the African endemic subtribe Anthosteminae is unresolved. The resulting trees support the monophyly of the tribe Stomatocalyceae while the tribe Hippomaneae does not consistently form a clade.
22.
23.
24.
Paul-Visse, Gesine, et al.
(författare)
Stem cells: hype or hope?
2002
Ingår i: Drug Discovery Today. - 1878-5832. ; 7:5, s. 295-302
Forskningsöversikt (refereegranskat) abstract
Stem cells undergo self-renewal and differentiate into multiple lineages of mature cells. The identification of stem cells in diverse adult tissues and the findings that human embryonic stem cells can be proliferated and differentiated has kindled the imagination of both scientists and the public regarding future stem cell technology. These cells could constitute an unlimited supply of diverse cell types that can be used for cell transplantation or drug discovery. The new options raise several fundamental ethical issues. This review gives an overview of the scientific basis underlying the hope generated by stem cell research and discusses current ethical and funding regulations.
25.
Ploj, Karolina, et al.
(författare)
Effects of maternal separation on brain nociceptin/orphanin FQ peptide levels in male Wistar rats
2002
Ingår i: Pharmacology, Biochemistry and Behavior. - 0091-3057 .- 1873-5177. ; 73:1, s. 123-129
Tidskriftsartikel (refereegranskat) abstract
Environmental manipulation early in life may induce persistent alterations in adult behaviour and physiology. In this study, we investigated the long-term effects of daily maternal separation, Days 1-21, on brain immunoreactive nociceptin/orphanin FQ (ir-N/OFQ) levels in male Wistar rats. The rat pups were separated in litters for 360 min (MS360) or 15 min (H15). Control rats were left undisturbed until weaning. Peptide levels were measured at 10 weeks of age. In the hypothalamus and periaqueductal gray, MS360 induced an increase in ir-N/OFQ levels in comparison with control rats. H15 rats had increased ir-N/OFQ levels in the hypothalamus and the medial prefrontal cortex compared with control animals. The rats were also tested at two occasions in an elevated plus-maze. An increased anxiety-like behaviour was shown in MS360 rats at weaning, whereas a decreased anxiety response was found at 9 weeks of age compared with control rats. The study shows that early life experiences induce long-term effects on behaviour, as well as brain N/OFQ levels.
26.
Ploj, Karolina, et al.
(författare)
Effects of melanocortin receptor ligands on ethanol intake and opioid peptide levels in alcohol-preferring AA rats
2002
Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 59:2, s. 97-104
Tidskriftsartikel (refereegranskat) abstract
Melanocortin (MC) peptides are suggested to play a role in opiate dependence, where they antagonise the addictive properties of opiates. To further study the involvement of the MCs in drug dependence, we analysed the effects of the MC(4)-receptor antagonist HS014 (1 nmol/rat), and the non-selective MC-receptor agonist MTII (1 nmol/rat), using i.c.v. administration, on ethanol intake in alcohol-preferring AA rats. The rats had access to ethanol during 40 days, resulting in a mean ethanol intake of 6.6 g/kg/day, before treatment. One group received only artificial cerebrospinal fluid solution. MTII caused a reduction in ethanol intake and ethanol preference, whereas HS014 was without effect. No effect on water intake was observed. A decrease in food intake was detected after MTII, whereas HS014 induced an increase in food intake. Analysis of dynorphin B and Met-enkephalin-Arg(6)Phe(7) immunoreactive levels revealed that MTII and HS014 altered opioid peptide levels in several brain areas and the pituitary gland of the rats with an established ethanol intake. This is the first report showing that manipulation of the MC-receptor system changes ethanol intake in chronically ethanol-drinking AA rats. In addition, manipulation of the MC system modulates ethanol-induced changes in opioid peptide levels.
27.
Ploj, Karolina, 1965-
(författare)
Involvement of the Opioid System in High Alcohol Consumption : Environmental and Genetic Influences
2002
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
It is well accepted that both inherent and environmental factors influence the pathogenesis of alcohol dependence. This thesis investigates the role of the opioid system in the initiation and maintenance of high ethanol intake. Ethanol-preferring C57BL/6J mice differ from ethanol-avoiding DBA/2J mice in that they exhibit lower basal levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7 (MEAP) in the nucleus accumbens, which may contribute to their divergent drug-taking behaviour. Chronic ethanol intake in C57BL/6J mice and repeated ethanol administration in Sprague-Dawley rats induce time-specific changes in dynorphin B and MEAP levels in regions, such as the nucleus accumbens and the ventral tegmental area, associated with reinforcing effects of drugs of abuse. Daily neonatal handling for 15 min (H15) and maternal separation for 360 min (MS360) during postnatal day 1-21 were used as models for environmental manipulation early in life. H15 in male rats results in decreased anxiety-like behaviour, whereas MS360 increases anxiety-like behaviour. Both H15 and MS360 induce changes in dynorphin B and MEAP levels especially in regions related to the hypothalamic-pituitary-adrenal (HPA) axis. In female rats, regions related to the HPA axis are unaffected by H15. This suggests a gender-specific involvement of opioids in the HPA axis response to stress. More rats in the MS360 group initiate ethanol consumption and have a higher ethanol intake later in life than the H15 group. The H15 group has particularly low ethanol intake and also differs with regard to neurochemistry compared to both MS360 and control groups, suggesting that H15 can induce long-term changes, protective against high ethanol intake. Specific changes in opioid receptor density are observed after chronic ethanol consumption, such as an increased κ-receptor density in several brain areas, as well as changes in δ-receptor density in the frontal cortex and the nucleus accumbens. Altogether, these results suggest that the opioid system plays an important role in the mechanisms underlying the initiation and maintenance of high ethanol intake.
28.
Ringbom, Therese, 1968-
(författare)
Bioassay Development for Identification of Cyclooxygenase-2 Inhibitors of Natural Origin
2002
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
To examine cyclooxygenase-2 (COX-2) inhibitory effects of natural compounds and structurally related compounds, a radiochemical assay for measuring inhibition of COX-2 and COX-1 catalysed prostaglandin biosynthesis was optimised. That process resulted in the development of a reliable assay for finding COX-2 inhibitors in plants, and for investigating plant constituents pertaining to the inhibition of COX-2 and COX-1. By means of bioassay-guided isolation of the plant Plantago major L., several inhibitors of COX-2 were found: ursolic, oleanolic, a-linolenic and linoleic acid. Subsequently, structural derivatives of these triterpenoids and fatty acids were investigated. The polyunsaturated and the thioether containing fatty acids were the most potent COX-2 and COX-1 inhibitors, with a-linolenic and all-(Z)-5-thia-8,11,14,17-eicosatetraenoic acid expressing selectivity toward COX-2. For rapid evaluation of plant constituents, a COX-2 assay using scintillation proximity assay-technology was used to evaluate 49 ubiquitous plant metabolites of different biosynthetic origin for inhibition of COX-2. Eugenol, cinnamaldehyde, and pyrogallol expressed inhibition. Later, in an attempt to find COX-2 inhibitors in plants, but without prior purification, several approaches to the surface plasmon resonance technique were examined, with the measurement of prostaglandin E2 being most successful.In mouse macrophage cells, two fatty acids were analysed for effects on COX-2 and iNOS, mRNA, protein, prostaglandin E2, and nitrite levels. 5-Thia-8,11,14,17-eicosatetraenoic acid decreased COX-2 protein expression.This thesis contributes to our growing knowledge of methods for measuring COX-2 inhibition, and also knowledge of COX-2 inhibitory effects of commonly occurring compounds in plants, herbal drugs and functional food. Thus the experimental results can facilitate future searches for new COX-2 inhibitors of natural origin.
29.
Sandström, Marie, 1960-
(författare)
Pharmacokinetics and Pharmacodynamics of Anti-Cancer Regimens : Emphasis on Busulphan and the Combination Therapies Epirubicin-Docetaxel and Fluorouracil-Epirubicin-Cyclophosphamide
2002
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Although the main reason for the lack of distinct dose-response and -toxicity relationships for anti-cancer agents is due to variability in pharmacodynamics, variability in pharmacokinetics may also contribute. Hence, not only describing and quantifying the relationship between pharmacokinetics and dose-limiting toxicities, but characterising the pharmacokinetics and its associated variability are of obvious importance in the process of developing dosing strategies for anti-cancer regimens. The aim of this thesis was to characterize the pharmacokinetics of fluorouracil (5-FU), epirubicin (EPI), 4-hydroxycyclophosphamide (4-OHCP), docetaxel (DTX) and busulphan (Bu) and, additionally, the relationship between the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide and epirubicin-docetaxel regimens. The pharmacokinetics of the combination EPI-DTX (ED) was studied in rats and patients, whereas the pharmacokinetics of Bu and 5-FU-EPI-4-OHCP (FEC) and haematological toxicity of the FEC and ED regimens was studied in patients only. All data analysis was performed using the NONMEM program. For all studied drugs, except 4-OHCP, course-to-course variability was found to be less than the inter-individual variability in the pharmacokinetic parameters and thereby therapeutic drug monitoring (TDM) may be a suitable approach for dose individualisation of all studied drugs, except CP. The development of haematological toxicity after treatment was described well by a semi-physiological model. In the case of the ED regimen, the model appeared to be able to estimate the respective contribution of EPI and DTX to the bone marrow toxicity. Thus, using the final PK-PD model in the individualisation process may further improve the probability of prescribing the most appropriate dose regimen for a patient early in the treatment period. A dosing program was constructed by implementing the final Bu population model into Excel, which resulted in a flexible and easy to use dosing tool. Similar programs may be constructed and used for dose individualisation of other anti-cancer drugs.
30.
Silwer, Louise, et al.
(författare)
Drug prescribing in public primary care centres : Results from prescription studies 1988-1997 in the county of Halland, Sweden
2002
Ingår i: Scandinavian Journal of Primary Health Care. - London : Informa Healthcare. - 0281-3432 .- 1502-7724. ; 20:4, s. 236-241
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE: To present the prescribing patterns of general practitioners (GPs) at public primary care centres (PPCCs) in Halland, a county in the south-west of Sweden. GP share of the total prescribing of different drug groups 1988-1997 is presented, as well as changes in patterns. DESIGN: A descriptive prescription study performed 3 months each year in 10 consecutive years. SETTING: Medical service and pharmacies in Halland. SUBJECTS: Prescriptions from about 100 GPs of PPCCs and 550 physicians of various other specialties. MAIN OUTCOME MEASURES: Percentages and absolute numbers of GPs prescribing. RESULTS: GPs prescribed 45% and 51% of the prescriptions from physicians in 1988 and 1997, respectively, while the cost shares were 40% and 42%. An increase in prescriptions was seen both in relative and in absolute numbers (from 117414 in 3 months in 1988 to 161012 in 1995). The increase in cost per DDD (defined daily dose) during the study period was 47% for GPs and 72% for other doctors. CONCLUSIONS: GP prescribing increased in both absolute and relative numbers, while the cost increase per DDD was moderate compared to other physicians.
