Munin

Development of liposomal formulation for green tea catechins targeted for the treatment of vaginal inflammation

2012-05-20T00:00:00Z

Trønnes, Johanne Naper
Green tea catechins are well known for their antioxidative and anti-inflammatory properties. In this connection, catechins are thought to be potential candidates in prevention and treatment of diseases caused by oxidative damage. In addition, catechins have been shown to be effective in the treatment of genital warts. However, they exhibit low bioavailability and poor solubility, which limits their use. This project focused on development of liposomal delivery system containing catechin and epicatechin, respectively, as mean to circumvent their physiochemical limitations and to enhance their biological activity. The formulation was intended for treatment of genital warts/vaginal inflammation. To become closer to an actual in vivo application, drug-bearing liposomes were incorporated in a mucoadhesive hydrogel. The optimized liposomal formulation for catechin was sonicated for 2 minutes and had an average diameter of 150 nm. These vesicles entrapped approximately 50 % of catechin. The corresponding liposomes prepared with epicatechin were found to have smaller size, however the entrapment was similar. Liposomes containing catechin were further incorporated in a hydrogel vehicle and the hydrogel was found to exhibit satisfactory adhesiveness and cohesiveness. In vitro release of catechin from liposomal preparations (both in a form of suspension and incorporated in hydrogel) was performed on Franz diffusion cells under condition simulating both the vaginal environment and physiological conditions. Liposomal hydrogels were found to provide sustained release of catechin. In conclusion, we can confirm that encapsulation of catechins in liposomes and their subsequent incorporation in hydrogels provides potentials for development of novel drug delivery systems for vaginal therapy with catechin.

Legemiddelbruk og bruk av kosttilskudd blant middelaldrende kvinner i Norge – Kvinner og kreft-studien

2012-05-20T00:00:00Z

Thoresen, May-Britt Storø
Bakgrunn: Det finnes lite informasjon om bruk og feilbruk av kosttilskudd i Norge. I internasjonale studier er det vist at kronikere er de som bruker mest kosttilskudd, og mange forteller ikke legen om denne bruken. Det finnes rapporterte tilfeller over interaksjoner mellom legemidler og kosttilskudd, men det finnes få studier om dette i Norge. Formål: Formålet med oppgaven er å beskrive forbruket av kosttilskudd (inkludert naturmidler, naturlegemidler og plantebaserte legemidler) blant en gruppe middelaldrene kvinner fra Kvinner og kreft-studien og relatere det til legemiddelbruk. Materiale og metode: Tversnittsstudien omfatter 3 231 av 4 500 kvinner som ble invitert til å donere blodprøver til Kvinner og kreft-studien i perioden 2003-2006. Kvinnene er i alderen 46-63 år, og er tilfeldig trukket ut fra den norske befolkningen. Prevalensen av kosttilskuddbruk (%) relatert til legemiddelbruk, menstruasjonsstatus, røyking og selvopplevd helse ble analysert vha. kji-kvadrattest. Sammenhengen mellom kosttilskudd-/legemiddelbruk og hhv. alder og BMI ble testet vha. ANOVA. Overforbruk ble undersøkt ved å se hvor mange som brukte flere enn ett kosttilskudd av typen “Omega-3” og/eller “Vitaminer, mineraler og antioksidanter”. Kombinasjoner av urter- og legemiddelbruk ble sjekket for kjente interaksjoner. Resultater: Responsraten var 72 %. Av de 3 231 kvinnene var det 73 % som bruker kosttilskudd, 65 % som brukte legemidler, og 48 % brukte begge deler. Dobbeltbrukerne var litt eldre, med opphørt menstruasjon, større grad av fedme, dårligere selvopplevd helse og de røyker mindre enn de som verken tar kosttilskudd eller legemidler. Legemiddelbrukerne hadde signifikant høyere prevalens av kosttilskuddbruk (74 %) enn ikke-brukeren (70 %), og kvinner i legemiddelkategorien “Astma, KOLS og allergi” brukte aller mest (79 %). “Vitaminer, mineraler og antioksidanter” er kosttilskuddkategorien hvor det var størst variasjon i prevalens mellom brukere og ikke-brukere av de ulike legemiddelkategoriene. Røykerne brukte signifikant mindre kosttilskudd, men mer legemidler for “Nervesystemet” enn ikke-røykerne. Bruk av mer enn ett Omega-3-produkt eller vitamintilskudd forekom blant hhv. 5 % og 12 % av deltakerne. Undersøkelsen avdekket svært høyt inntak av bl.a. E- og D-vitamin hos to kvinner, uten at dette var undersøkt kvantitativt. Det ble ikke funnet noen kjente interaksjoner mellom legemidler og urtene. Konklusjon: Det er en sammenheng mellom bruk av legemidler og kosttilskudd. Nær halvparten (48 %) av middelaldrende kvinner tar kosttilskudd mens de står på legemiddelbehandling. De er noe eldre med opphørt menstruasjon, større grad av fedme, dårligere selvopplevd helse og de røyker mindre enn de andre brukerkategoriene. Oppgaven viser et potensiale for overforbruk av vitaminer blant middelaldrende kvinner, mens forekomsten av kjente interaksjoner mellom legemidler og urter er ubetydelig.

Development of chitosan-coated liposomes for improved therapy of vaginal infections: clotrimazole as model drug

2012-05-01T00:00:00Z

Jøraholmen, May Wenche Bakke
For many drugs the vaginal route of administration is favorable, particularly for local therapy of specific gynecological diseases such as vaginal infections. A large variety of pharmaceutical preparations have been developed for vaginal delivery, nevertheless, the efficiency of currently available dosage forms is often limited by their poor retention time at the vaginal site. Physiological changes and the self-cleansing action of the vaginal tract remain a challenge in formulation development. The aim of this study was development and characterization of mucoadhesive liposomes capable to improve vaginal delivery of clotrimazole. Clotrimazole was incorporated in liposomes by the mechanical dispersion method and the liposomal suspension sonicated to desired vesicle size. Liposomes were characterized for their size, polydipersity and clotrimazole entrapment. Polymer-coating was used to improve the mucoadhesive properties, and chitosan was chosen as a coating material. Chitosan coating (0.1 and 0.6 %, w/v) was performed on liposomes free from unentrapped clotrimazole. In vitro drug release from chitosan-coated liposomes was compared to release from non-coated liposomes and free clotrimazole. Chitosan-coated vesicles were able to prolong the release of entrapped clotrimazole to greater extent than non-coated liposomes. Cow vaginal mucosa was used as model mucosa in both penetration study and mucoadhesion testing and the preliminary data indicate that clotrimazole stays in vaginal tissue, rather than penetrating though the tissue. The experiments confirmed potential of chitosan-coated phospholipid vesicles in treatment of local vaginal diseases.

Biological and chemical characterization of ianthelline isolated from a marine sponge

2011-05-20T00:00:00Z

Siiri, Anette Olli
Abstract Previous studies of sponges have led to the discovery of the commercially available drugs cytarabin and vidarabin. The arctic sponge Stryphnus fortis showed antibacterial and anticancer activity in the primary screening in the MabCent screening program; most likely from more than one compound. Dereplication with TOF-MS suggested the presence of ianthelline as one of the active compounds. In order to purify large amounts of the ianthelline, the extract was fractionated using flash chromatography and the fractions found to contain the active compound were combined and submitted to semi-preparative HPLC for further purification. TOF-MS, MS/MS and 1H, 13C, HMBC and HSQC NMR confirmed the presence of ianthelline in the product from the semi-preparative HPLC. Ianthelline was tested for antibacterial activity, antioxidant activity and anticancer activity. Ianthelline had a dose-response relationship antibacterial activity against E. coli, E. faecalis, P. aeruginosa, S. aureus and MRSA, the activity was highest for S. aureus and MRSA. Ianthelline showed only a slight antioxidant activity compared to curcumin. Ianthelline showed anticancer activity against A2058 (melanoma), MCF7 (breast carcinoma) and HT29, but also killed normal lung fibroblasts (MRC5), indicating a general toxicity. Anticancer activity occurred after a minimum of 24 hours exposure of ianthelline against A2058 and normal lung fibroblast (MRC5), and after a minimum of 48 hours exposure of ianthelline against HT29.

Optimization of antimicrobial wound dressings: liposomal hydrogels with mupirocin

2012-05-20T00:00:00Z

Nguyen, Truc Phuong
Skin injuries represent an important health problem that needs to be managed properly in order to avoid serious consequences in terms of morbidity, disability and life quality. The current focus in wound therapy is on upholding the moisture balance in the wound bed and protection against pathogenic invasion. Wound dressings in a form of hydrogels incorporating antimicrobials, such as the antibiotic mupirocin, can be applied to control dermal infections and thereby ensure optimal wound healing. Drug-in-liposomes-in-hydrogel may additionally provide prolonged contact between drug and wounded area, reducing the need for frequent application of wound dressing. Size analysis of sonicated liposomes indicated that the particles were smaller than 300 nm, optimal for topical administration onto the skin. Assessment of anti-biofilm effect of liposomally entrapped and free mupirocin showed that both formulations had an impact on biofilm formation and planktonic bacteria, however no clear advantage of liposomal formulation over free drug was seen. Liposomal hydrogels in which mupirocin is incorporated in liposomes, are safe and have potential to be used as wound dressing assuring maintenance of a moist wound environment. Chitosan liposomal hydrogels would be recommended for wounds with exudates, as their absorbing properties were better than for Carbopol-based hydrogels.

Late Paleozoic-Cenozoic fault correlation and characterization of fault rocks in western Troms, North Norway

2013-05-29T00:00:00Z

Koehl, Jean-Baptiste Philippe
The present work focuses on the mapping and description of onshore brittle fault zones on the SW Barents Sea Margin, within gneisses and granitic intrusions belonging to the West Troms Basement Complex. The description of the brittle structures includes the geometry, kinematics and fault rock characteristics, using DEM satellite imaging, structural field work and a microstructural analysis of the fault rocks. As a result of the present study,two major sets of onshore brittle faults have been observed, trending NNE-SSW and ENE-WSW,and they are tentatively correlated in two, NE-SW trending fault complexes: the Rekvika and the Vestfjorden-Vanna fault complexes. These fault complexes run parallel to the Troms-Finnmark fault complex that borders major offshore sedimentary basins in the NW. On the one hand, the Vestfjorden-Vanna fault complex defines the southeastern boundary of the West Troms Basement Complex towards the Caledonian nappes, and is made of wide fault zones that have experienced major displacement (ca. 1-3km). On the other hand, the Rekvika fault complex is considered as an intra-horst fault system composed of narrow fault zones that are thought to have accommodated low amounts of displacement (> 250 m). On a local scale, the fault zones display similarities in attitude (trend and dip) with the Caledonian and Precambrian fabrics, indicating a possible influence of pre-existing zones of weakness on brittle faulting. The dominant deformation mechanism (cataclastic flow) indicates pressure range about 0.2-0.3 GPa, i.e. 5-10 km depth for the formation of the cataclastic fault rocks, and these fault rocks contain mineral assemblages that generally indicate temperatures about 350-500ᵒC. This suggests that the West Troms Basement Complex has been largely uplifted later on, until present level. The NNE-SSW and ENE-WSW trending fracture sets are believed to have formed synchronously due to WNW-ESE extension, during an early stage of rifting in the Permian-Early Triassic. The NNE-SSW trending faults likely represent the main fault system, orthogonal to the extension direction, and the ENE-WSW trending faults may correspond to oblique transfer zones that link the NNE-SSW fault segments. An alternative model implies NW-SE trending transfer zones to link the NNE-SSW trending faults. A late stage of minor reverse reactivation of the NNE-SSW and ENE-WSW trending faults, and the development of NW-SE striking fractures are tentatively correlated to ridge-push forces during the opening of the North Atlantic in the Eocene.

Estimation of travel mode choice for domestic tourists to Nha Trang using the multinomial probit model

2013-01-01T00:00:00Z

Can, Vo Van
The purpose of this study is to examine how the characteristics of domestic tourists and attributes of travel modes influence the tourists’ modal choice to Nha Trang, Viet Nam by applying the multinomial probit model. The analysis is based on primary data surveyed from tourists visiting Nha Trang in March, 2011. A total of 402 valid samples were used from 554 initial samples. The study provides several important findings concerning tourists’ modal choice. Travel time per kilometer, per-kilometer travel cost to income ratio, mode quality variables, and income are key elements in explaining the tourists’ modal choice decision. In addition, tourists with a lower income tend to be more sensitive to change in per-kilometer cost. Furthermore, the high-income tourists are much more likely to choose plane or train rather than coach. Understanding the tourists’ modal choice behavior may help tourism transport companies to develop appropriate marketing strategies.
This article is part of Vo Van Can's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5203

Landform assemblages in inner Kongsfjorden, Svalbard: evidence of recent glacial (surge) activity

2013-05-15T00:00:00Z

Streuff, Katharina Teresa
Swath bathymetry and chirp data have been used to investigate the submarine landform assemblages in inner Kongsfjorden, Svalbard, to reconstruct glacial dynamics during the Late Holocene. Multiple sets of landforms include two types of glacial lineations (groove-ridge features and small, drumlinoid ridges), terminal moraines and associated debris lobes, as well as small push moraines, and indicate repeated surge activity during the last 150 years for four of the five tidewater glaciers terminating in inner Kongsfjorden. Aside from confirming previously documented surges of Kronebreen in 1869, of Kongsvegen, in 1948, and of Blomstrandbreen in 1960, the local bathymetry also indicates a surge of Kongsbreen in 1897, a glacier that has so far been regarded as a non-surge type glacier. A conceptual model was developed to summarize the surge-induced landform assemblages in Kongsfjorden, and to compare them with other models from terrestrial and marine settings. Striking similarities exist between the Kongsfjorden model and landform assemblages documented for other Spitsbergen fjords. However, eskers and crevasse-fill ridges, the latter thought to be the only landform certainly indicative of glacier surges, lack in Kongsfjorden. Furthermore, the small, drumlinoid ridges inferred to be suggestive of the past ice flow direction in the study area seem to have more in common with glacial lineations generated by surging glaciers on land. The acoustic data was supplemented with two sediment cores from Kongsfjorden’s innermost basin. The reworked glacimarine deposits at the base of the more proximal core reflect proximal conditions, as they are part of a debris lobe that formed on the distal flank of the terminal moraine deposited during the 1948 surge of Kongsvegen. The stratified muds from the second core contain varying amounts of clasts and also occur on top of the debris lobe. They reveal a relatively distal glacimarine environment mainly influenced by suspension settling from turbid meltwater emanating from Kronebreen or Kongsvegen. Geochemical fluctuations indicate temporal variations in the sediment supply from the two glaciers after 1948. The few landforms in the outer parts of the study area suggest glacial activity unrelated to the glacier surges. Together with the landforms previously documented from outer Kongsfjorden and its adjacent trough (Kongsfjordrenna), the mega-scale glacial lineations in the outer part of the study area indicate part of a landform assemblage deposited from a fast-flowing ice stream during the Last Glacial Maximum.

Retinopathy with and without diabetes: Risk factors and visual impairment.

2013-03-22T00:00:00Z

Bertelsen, Geir
Diabetic retinopathy is a well-known complication of diabetes and a major cause of visual impairment and blindness in developed countries. We explored visual impairment and diabetic retinopathy among participants with diabetes in the Tromsø Eye Study. The prevalence of visual impairment (corrected Snellen visual acuity < 20/40) was 4.1% in the better-seeing eye. We found no legally blind participants. The prevalence of diabetic retinopathy was 26.9% and macular edema 3.9%. In a multivariable logistic regression model, retinopathy was associated with longer diabetes duration, insulin use, non-fasting glucose and urinary albumin excretion. We found a very low microalbuminuria cut-off level for increased risk of diabetic retinopathy (urinary albumin-creatinine ratio > 1.16 mg/mmol). Visual impairment and diabetic retinopathy were also explored in diabetes patients recruited from general practitioners in a multi-centre study conducted in Tromsø, Tønsberg and Stavanger. In this study the prevalence of visual impairment (corrected Snellen visual acuity < 20/40) was 5.4% and one participant was legally blind. The prevalence of diabetic retinopathy was 28.2%. This study also showed that about one third of the diabetes patients did not attend at least biannual eye examination as recommended by the national guidelines. Retinopathy lesions, such as microaneurysms and retinal haemorrhages, are also common in subjects without diabetes. We explored retinopathy in subjects without diabetes in the Tromsø Eye Study, and the overall prevalence of retinopathy was 14.8%. Men had a higher prevalence of retinopathy compared to women (15.9% vs. 14.0%, p=0.04). In men retinopathy was associated with hypertension and HbA1c. In women retinopathy was associated with age, hypertension and urinary albumin excretion. In women, the microalbuminuria cut-off level for increased risk of retinopathy was very low (urinary albumin-creatinine ratio > 0.43 mg/mmol). Visual impairment was also explored in a general population using data from both diabetic and non-diabetic participants in the Tromsø Eye Study and the overall prevalence of visual acuity < 20/60 was 1.2%.
The papers of this thesis are not available in Munin:
1. Bertelsen G, Erke MG, von Hanno T, Mathiesen EB, Peto T, Sjølie AK and Njølstad I.: 'The Tromsø Eye Study: study design, methodology and results on visual acuity and refractive errors', Acta Ophthalmologica (2012), online before print, available at http://dx.doi.org/10.1111/j.1755-3768.2012.02511.x
2. Bertelsen G, Peto T, Lindekleiv H, Schirmer H, Solbu MD, Toft I, Sjølie AK and Njølstad I.: 'Tromsø Eye Study: prevalence and risk factors of diabetic retinopathy', Acta Ophthalmologica (2012), online before print, available at http://dx.doi.org/10.1111/j.1755-3768.2012.02542.x
3. Bertelsen G, Peto T, Lindekleiv H, Schirmer H, Solbu MD, Toft I, Sjølie AK and Njølstad I.: 'Sex differences in risk factors for retinopathy in non-diabetic men and women. The Tromsø Eye Study' (manuscript)
4. Kilstad HN, Sjølie AK, Gøransson L, Hapnes R, Henschien HJ, Alsbirk KE, Fossen K, Bertelsen G, Holstad G and Bergrem H.: 'Prevalence of diabetic retinopathy in Norway: report from a screening study', Acta Ophthalmologica (2012), vol. 90(7):609–612, available at http://dx.doi.org/10.1111/j.1755-3768.2011.02160.x

Geomorfologi av glasiale sedimenter basert på 3D seismikk fra Nordkappbanken, SV Barentshav

2013-05-15T00:00:00Z

Richardsen, Morten
Den kvartære lagpakken er analysert med fokus på glasial geomorfologi. Dette er gjort ved bruk av tre-dimensjonale (3D) seismiske data fra Nordkappbanken, sørvestlige Barentshav. I tillegg til havbunnen er det identifisert 2 begravde flater som begge er påvirket av glasiale prosesser. Geomorfologien til den stratigrafisk grunneste av de begravde flatene viser flere store depresjoner som er opp til 65 meter dype, 2 til 6 km brede og dekker et lateralt område på til sammen rundt 60 km2. Rygger av sedimenter like nord-nordvest for depresjonene har nesten samme form og volum som disse, og sammen er depresjonene og ryggene tolket til å representere “hill-hole pairs”. På samme flate er det observert rette langstrakte furer orientert sør-sørøst / nord-nordvest, tolket til å være mega-skala glasiale lineasjoner formet av raske isstrømmer. Mega-skala glasiale lineasjoner sett i sammenheng med “hill-hole pairs” indikerer pro- eller subglasial glasitektonisk deformasjon. Alderen til den begravde flaten er rundt 17.1 til 16.6 kal ka, som tilsvarer en tid da isdekket i Barentshavet trakk seg tilbake. Perioder med stillstand i tilbaketrekningen og fremrykk av isdekket har trolig spilt en stor rolle for de glasitektoniske prosessene i studieområdet. Seismiske data indikerer forekomst av grunn gass i områdene med glasitektoniske formelementer. Denne gassen kan ha ført til dannelse av svakhetssoner og ustabile sedimenter, og har trolig medvirket til glasitektonisk erosjon. Studieområdet ligger i dag innenfor stabilitetssonen for gasshydrater med struktur II, og det er indikert at denne typen gasshydrater kan ha medvirket til de glasitektoniske prosessene. På bakgrunn av at gasshydrater med struktur II inneholder tyngre hydrokarboner, og siden det er grunn gass i studieområdet er det sett nærmere på mulige migrasjonsruter for fluider. Et tett nettverk av forkastninger, saltdiapirer og påviste hydrokarboner i den underliggende berggrunnen indikerer migrasjon av tyngre hydrokarboner fra dypere hydrokarbonreservoarer opp i de grunne avsetningene. Depresjonene er dype og opptrer også på den stratigrafisk dypeste begravde flaten (URU), slik at den underliggende sedimentære berggrunnen er erodert. Denne erosjonen observeres bare i områder der den underliggende sedimentære berggrunnen består av kritt-avsetninger, noe som tyder på at kritt-enheter kan ha vært svakhetssoner som ble erodert lettere enn omkringliggende bergartsenheter. Avslutningsvis er en mulig relasjon mellom glasitektonikken og de store formelementene Nordkappbanken bueformede rygg og Nordkappbanken sedimentære kile vurdert. Nordkappbanken bueformede rygg er tolket til å være en endemorene avsatt under isdekkets fremrykk for 16 kal ka, og den glasitektoniske deformasjonen diskuteres til å ha en sammenheng med dette fremrykket. “Hill-hole pairs” er lokalisert under denne endemorenen, og det er foreslått at de kan være et resultat av proglasial oppskyving av sedimenter. Det er også foreslått at det har vært store mengder sedimentrikt smeltevann involvert i deglasiasjonen, noe som førte til at Nordkappbanken sedimentære kile ble avsatt.