108 results on '"Torp, M"'
Search Results
2. Nonintensive topical gentamicin treatment of patients with severe epidermolysis bullosa caused by nonsense mutations.
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Sandanger, Ø., Torp, M. K., Glesaaen, A., Nilsen, H. R., and Sitek, J. C.
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- 2024
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3. Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis
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Torp, M-K, Ranheim, T., Schjalm, C., Hjorth, M., Heiestad, C. M., Dalen, K. T., Nilsson, Per H., Mollnes, T. E., Pischke, S. E., Lien, E., Vaage, J., Yndestad, A., Stenslokken, K-O, Torp, M-K, Ranheim, T., Schjalm, C., Hjorth, M., Heiestad, C. M., Dalen, K. T., Nilsson, Per H., Mollnes, T. E., Pischke, S. E., Lien, E., Vaage, J., Yndestad, A., and Stenslokken, K-O
- Abstract
The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 +/- 9% in C3KO vs. 22 +/- 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.
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- 2022
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4. Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis
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Torp, M-K., primary, Ranheim, T., additional, Schjalm, C., additional, Hjorth, M., additional, Heiestad, C.M., additional, Dalen, K. T., additional, Nilsson, P. H., additional, Mollnes, T. E., additional, Pischke, S. E., additional, Lien, E., additional, Vaage, J., additional, Yndestad, A., additional, and Stensløkken, K-O., additional
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- 2022
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5. Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer
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Fjord-Larsen, L, Kusk, P, Emerich, D F, Thanos, C, Torp, M, Bintz, B, Tornøe, J, Johnsen, A H, and Wahlberg, L U
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- 2012
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6. The use of Ki-67/MIB-1 immunostaining in human gliomas: P39
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Torp, S. H., Mørk, J. N., Torp, M. O., and Skjulsvik, A. J.
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- 2014
7. Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure
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Torp, M., Brnd, L., Nielsen, J. B., Nielsen, S., Christensen, S., and Jonassen, T. E. N.
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- 2012
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8. Improving the safety of organic vegetables
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Johannessen, G, primary and Torp, M, additional
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- 2005
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9. Transgenic hybrid aspen with altered defensive chemistry: a model system to study the chemical basis of resistance?
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Witzell, J., primary, Karlsson, M., additional, Rodriguez-Buey, M., additional, Torp, M., additional, and Wingsle, G., additional
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- 2005
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10. Development of an e-learning program to enhance and maintain the knowledge of experienced RTT's
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Gornitzka, J., Akselbo, L., Torp, M., Matthai, V., Bjorn, T., and Gottlieb, K. L.
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- 2019
11. Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure
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Torp, M., Brønd, L., Hadrup, N., Nielsen, J. B., Prætorius, J., Nielsen, S., Christensen, S., and Jonassen, T. E. N.
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- 2007
12. Moniliformin in Norwegian grain
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Uhlig, S., Torp, M., Jarp, J., Parich, A., Gutleb, A. C., and Krska, R.
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- 2004
13. PO-1130 Development of an e-learning program to enhance and maintain the knowledge of experienced RTT’s
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Gornitzka, J., primary, Akselbo, L., additional, Torp, M., additional, Matthäi, V., additional, Bjørn, T., additional, and Gottlieb, K.L., additional
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- 2019
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14. Perhevapaat 2013 -väestökyselyn toteutus. Tiedonkeruu, aineiston edustavuus ja perustietoja vastaajista
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Juutilainen, V-P, Saarikallio-Torp, M, and Haataja, A
- Abstract
Perhevapaat 2013 -väestökysely on Kelan tutkimusosaston ja Terveyden ja hyvinvoinnin laitoksen (THL) Politiikan seuranta- ja vaikuttavuusyksikön yhteydessä toteuttama laaja väestökysely. Kyselyn kohderyhmänä olivat vuonna 2011 lapsen saaneet äidit ja isät. Kysely oli kolmas osa vastaavien kyselyiden sarjaa, joista aiemmat on toteutettu vuosina 2001 ja 2006. Tämänkertainen kysely toteutettiin ensimmäistä kertaa täysin sähköisesti kun taas aiemmat ovat olleet perinteisiä paperikyselyitä. Kyselyn perusjoukon muodostivat vuonna 2011 lapsen saaneet äidit ja isät, jotka olivat käyttäneet vanhempainpäivärahoja eli äitiys-, isyys- tai vanhempainrahaa kyseisestä lapsesta, joille löytyi Kelaan ilmoitettu sähköpostiosoite ja jotka asuivat kyselyhetkellä Suomessa. Sähköpostiosoite löytyi kaikkiaan 75,7 prosentille etuuksia käyttäneistä äideistä ja 68,3 prosentille etuuksia käyttäneistä isistä. Otannan yhteydessä äidit jaettiin kolmeen ryhmään, perusotoksen äiteihin, monikkoäiteihin ja 18–22-vuotiaisiin nuoriin äiteihin. Perusotoksen äidit muodostavat aineiston perustan ja tästä ryhmästä tehtyyn otokseen kuului kaikkiaan 6 914 äitiä. Perusotoksen äitien lisäksi erillisaineistoja varten kyselyyn otettiin mukaan kaikki monikkoäidit ja nuorten äitien ryhmää kasvatettiin täydennysotoksilla. Kyselyyn tuli mukaan kaikkiaan 8 297 äitiä. Isien puolella isäotoksen koko oli 6 781 isää. Otos toteutettiin jakamalla isät ensin kahteen ryhmään käytettyjen perhevapaapäivien mukaan ja ottamalla näistä ositteista omat otoksensa. Äitien perusotoksessa kyselyn vastausaste oli 44,1, monikkoäideillä 38,4 ja nuorilla äideillä 34,6 prosenttia. Isien vastausaste oli 32,3 prosenttia. Äitiaineistojen edustavuus on hyvä ja sitä tullaan käyttämään varsinaisissa analyyseissä sellaisenaan, kun taas isäkyselyssä enemmän vanhempainpäivärahoja käyttäneet isät olivat aktiivisempia vastaamaan kuin vähän vanhempainpäivärahoja käyttäneet. Isäaineistossa ryhmien suhteelliset osuudet painotettiin vastaamaan perusjoukkoa. Kyselyllä saadaan paljon tietoa suomalaisista pienten lasten perheistä. Voimme kuvailla perheitä, saada tietoa syistä, miksi perheet tekivät erilaisia lapsenhoitovalintoja ja saada tietoa perheiden mielipiteistä liittyen perhevapaajärjestelmään. Esimerkiksi perusäitien kyselyssä ja isäkyselyssä saadut vastaukset olivat hyvin samankaltaisia, kun tarkasteltiin vastaajien käsitystä perheen toimeentulosta, omista tai puolison tuloista sekä perhevapaiden käytöstä. Runsaat 40 prosenttia sekä äideistä että isistä oli puolestaan sitä mieltä, että tuolloinen mahdollisuus myöhentää isäkuukautta vaikutti ainakin jonkin verran siihen, että isät käyttivät oikeuttaan. Sen sijaan isät olivat äitejä hieman useammin valmiita kehittämään perhevapaajärjestelmää. Mielipiteet, jotka koskivat päivähoito-oikeuksien rajaamista, jakautuivat työttömyystaustan mukaan. Vastaajat, joiden perheessä oli työttömyyttä, suhtautuivat muita kielteisemmin päivähoito-oikeuksien rajoittamiseen. Mielipiteisiin eri aiheista vaikuttaa niin vastaajien ja heidän perheidensä tilanne kuin heidän kokemuksensa näistä järjestelmistä. Lapsiperheet ovat erilaisia ja niiden joukossa on useita erilaisia ryhmiä. Kyselyaineistoja analysoitaessa on tärkeää huomioida nämä tekijät. 2., korjattu painos (16.3.2017)
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- 2016
15. Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure
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Torp, M, Brønd, L, Nielsen, J B, Nielsen, Søren, Christensen, S, and Jonassen, T E N
- Abstract
Aim: Congestive heart failure (CHF) is associated with increased renal sympathetic nerve activity and renal sodium retention. Rats with CHF display increased expression of the Na-K-2Cl cotransporter (NKCC2) in the renal medullary thick ascending limb of the loop of Henle (mTAL), and arginine vasopressin (AVP)-stimulated cAMP formation in mTAL segments is increased in rats with CHF. The aim of the study was to investigate the role of RSNA on cAMP formation and NKCC2 expression in mTAL in rats with CHF. Methods: Congestive heart failure was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Bilateral surgical renal denervation (DNX) was performed 3 weeks later. Two weeks after DNX, mTAL segments were isolated and stimulated with AVP. Results: Congestive heart failure rats displayed increased mTAL NKCC2 expression (2.5 ± 0.5 vs. 1 ± 0.2 in Sham rats), which was abolished by DNX. Bilateral denervation decreased basal cAMP levels in unstimulated tubules from CHF rats (CHF: 12.56 ± 7.73 fmol μg(-1) protein vs. DNX-CHF: 7.94 ± 4.33; P
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- 2011
16. Nordic students abroad. Student mobility patterns, student support systems and labour market outcomes
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Saarikallio-Torp, M, Wiers-Jenssen, J, and eds.
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study abroad ,opiskelu ulkomailla ,työllistyminen ,labour market outcomes ,korkeakoulututkinnot ,työhönsijoittuminen ,opiskelijaliikkuvuus ,academic degree ,student mobility ,employment ,employment abroad ,graduates ,tutkinnon suorittaneet ,työskentely ulkomailla - Abstract
151 s. Tämän tutkimuksen tarkoitus on tarkastella ulkomailla korkeakoulututkintonsa suorittaneita pohjoismaalaisia ja heidän työmarkkinoille sijoittumistaan vertaamalla heitä kotimaassa korkeakoulututkinnon suorittaneisiin. Tutkimus tarjoaa arvokasta uutta tietoa opiskelijaliikkuvuudesta ja sen vaikutuksista. Keskeisimmät tutkimuskysymykset ovat: 1) Keitä ulkomailla opiskelevat pohjoismaalaiset ovat? 2) Palaavatko he takaisin kotimaahansa valmistumisensa jälkeen? 3) Löytävätkö he koulutusta vastaavaa työtä? 4) Pystyvätkö he hyödyntämään kansainvälistä osaamistaan työmarkkinoilla? 5) Minkälainen rooli opintotukijärjestelmällä on opiskelijaliikkuvuudessa? Tutkimuksessa käytetty kyselyaineisto perustuu Nordic Graduate Surveyyn (NGS), joka toteutettiin vuonna 2007 Suomessa, Islannissa, Norjassa ja Färsaarilla. Aineisto sisältää tietoa yhteensä 6 500 vastaajalta, joista 2 600 on suorittanut korkeakoulututkinnon ulkomailla. Tämän lisäksi tutkimuksessa on hyödynnetty kahta tanskalaista aineistoa. Vaikka ulkomailla korkeakoulututkinnon suorittaneiden välillä on yhtäläisyyksiä eri Pohjoismaissa, on maiden välillä myös eroja. Useammalla ulkomailla tutkinnon suorittaneella on korkeasti koulutetut vanhemmat kuin kotimaassa opiskelleella. Lisäksi heidän vanhempansa tai he itse olivat useammin asuneet ulkomailla jo ennen opiskelujen aloittamista kuin kotimaassa opiskelleet tai näiden vanhemmat. Niiden ulkomailla tutkinnon suorittaneiden osuus, jotka ovat palanneet valmistumisensa jälkeen takaisin kotimaahan, vaihtelee suuresti eri Pohjoismaissa. Osuudet ovat suurimmat Norjassa ja Islannissa. Julkinen opintotukijärjestelmä on tärkein ulkomaisten opintojen rahoitusmuoto, vaikkakin opintorahan ja -lainan suhteellinen osuus vaihtelee maittain. Ulkomailla tutkinnon suorittaneiden työmarkkinoille sijoittuminen näyttää olevan jonkin verran vaikeampaa kuin kotimaassa opiskelleiden. Ulkomailla tutkinnon suorittaneet työskentelevät useammin kansainvälisissä työtehtävissä kuin kotimaassa opiskelleet – myös kotimaassa asuessaan. 15,00 euroa
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- 2010
17. Downregulation of high-isoelectric-point extracellular superoxide dismutase mediates alterations in the metabolism of reactive oxygen species and developmental disturbances in hybrid aspen
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Srivastava, V., Schinkel, H., Witzell, J., Hertzberg, M., Torp, M., Srivastava, M.K., Karpinska, B., Melzer, M., Wingsle, G., and Publica
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- 2007
18. Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure
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Torp, M, Brønd, L, Hadrup, N, Nielsen, J B, Praetorius, J, Nielsen, S, Jonassen, T E N, Christensen, Sten, Torp, M, Brønd, L, Hadrup, N, Nielsen, J B, Praetorius, J, Nielsen, S, Jonassen, T E N, and Christensen, Sten
- Abstract
Udgivelsesdato: 2007-Aug, INTRODUCTION: Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl-cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type-1 (AT(1)) blockade with losartan. AIM: In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT(1) receptor blockade on this system. METHOD: CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM-operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day(-1) i.p.). RESULTS: CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10(-6) m) stimulated cAMP levels were significantly increased in CHF rats (25.52 +/- 4.49 pmol cAMP microg(-1) protein, P < 0.05) compared to Sham rats (8.13 +/- 1.14 pmol cAMP microg(-1) protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 +/- 1.93 fmol microg(-1) protein vs. Los-CHF: 7.49 +/- 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 +/- 0.59 vs. Los-SHAM: 4.75 +/- 0.71). AVP-mediated cAMP accumulation was absent in both groups treated with losartan (Los-SHAM: 4.75 +/- 0.71 and Los-CHF: 7.49 +/- 1.08). CONCLUSION: The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT(1) receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption.
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- 2007
19. Influence of agronomic and climatic factors onFusariuminfestation and mycotoxin contamination of cereals in Norway
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Bernhoft, A., primary, Torp, M., additional, Clasen, P.-E., additional, Løes, A.-K., additional, and Kristoffersen, A.B., additional
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- 2012
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20. Alternaria and Fusarium in Norwegian grains of reduced quality - a matched pair sample study
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Kosiak, B., Torp, M., Skjerve, E., Andersen, Birgitte, Kosiak, B., Torp, M., Skjerve, E., and Andersen, Birgitte
- Abstract
The occurrence and geographic distribution of species belonging to the genera Alternaria and Fusarium in grains of reduced and of acceptable quality were studied post-harvest in 1997 and 1998. A total of 260 grain samples of wheat, barley and oats was analysed. The distribution of Alternaria and Fusarium spp. varied significantly in samples of reduced quality compared with acceptable samples. Alternaria spp. dominated in the acceptable samples with A. infectoria group as the most frequently isolated and most abundant species group of this genus while Fusarium spp. dominated in samples of reduced quality. The most frequently isolated Fusarium spp. from all samples were F avenaceum, E poae, F culmorum and E tricinctum. Other important toxigenic Fusarium spp. isolated were F graminearum and E equiseti. The infection levels of F graminearum and F culmorunt were significantly higher in the samples of reduced quality. The results indicated a negative interaction between E graminearum and Alternaria spp. as well as between F graminearum and other Fusarium spp.
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- 2004
21. An integrated taxonomic study of Fusarium langsethiae, Fusarium poae and Fusarium sporotrichioides based on the use of composite datasets
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Schmidt, H., Adler, A., Holst-Jensen, A., Klemsdal, S.S., Logrieco, A., Mach, R.L., Nirenberg, H.I., Thrane, Ulf, Torp, M., Vogel, R.F., Yli-Mattila, T., Niessen, L., Schmidt, H., Adler, A., Holst-Jensen, A., Klemsdal, S.S., Logrieco, A., Mach, R.L., Nirenberg, H.I., Thrane, Ulf, Torp, M., Vogel, R.F., Yli-Mattila, T., and Niessen, L.
- Abstract
An integrated systematic study was carried out to clarify the taxonomical position and relationship of Fusarium langsethiae to other taxa within the Fusarium section Sporotrichiella. Strains of this species were compared with strains of the closely related species Fusarium poae and Fusarium sporotrichioides using a composite dataset. This set consisted of DNA sequences derived from the ribosomal internal transcribed spacer (ITS) regions, partial sequences of the ribosomal intergenic spacer (IGS) region, the beta-tubulin and translation elongation factor-1 alpha (EF-1alpha) genes, AFLP fingerprints, chromatographic data on secondary metabolites and morphological data and growth characteristics. From these combined data, a consensus matrix was calculated by taking the mean of all pairwise distances between single isolates over all separate datasets. The consensus matrix was used as the basis for the construction of a UPGMA dendrogram and a multidimensional scaling, both of which revealed a clear separation of the three taxa. Partial IGS, EF-1alpha and beta-tubulin sequence-as well as chromatography-and AFLP-derived similarities turned out to be comparably consistent, while ITS sequence- and morphology-derived similarity matrices were rather divergent.
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- 2004
22. Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer
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Fjord-Larsen, L, primary, Kusk, P, additional, Emerich, D F, additional, Thanos, C, additional, Torp, M, additional, Bintz, B, additional, Tornøe, J, additional, Johnsen, A H, additional, and Wahlberg, L U, additional
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- 2011
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23. Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure
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Torp, M., primary, Brønd, L., additional, Nielsen, J. B., additional, Nielsen, S., additional, Christensen, S., additional, and Jonassen, T. E. N., additional
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- 2011
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24. The prevalence and distribution of Fusarium species in Norwegian cereals: a survey
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Kosiak, B., Torp, M., Skjerve, E., Thrane, Ulf, Kosiak, B., Torp, M., Skjerve, E., and Thrane, Ulf
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In the period 1994-1996 a post-harvest survey was conducted in wheat, barley and oats to assess the occurrence and geographic distribution of Fusarium species in Norwegian cereals. The number of samples investigated was adjusted proportionally to the production of each cereal species within the regions. A total of 695 grain samples were analysed. The amount of Fusarium infection varied with cereal species and region of origin. The most frequently isolated Fusarium spp. from all samples were F. avenaceum, F. poae, F. tricinctum and F. culmorum. Other important toxigenic Fusarium spp. were F. graminearum, "powdery F. poae ", F. equiseti and F. sporotrichioides . A north-south gradient was valid for F. tricinctum, F. poae and in 1994 for "powdery F. poae ". In 1994 "powdery F. poae " was the most abundant potential producer of HT-2 and T-2 toxins in Norwegian cereals. Distribution of F. graminearum and F. culmorum demonstrated in this study , corresponded to previously reported DON-distribution, although DON seems to be produced by different species in different regions. Distribution of the isolated Fusarium species and comparison between cereals and locations are discussed.
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- 2003
25. LessFusariuminfestation and mycotoxin contamination in organic than in conventional cereals
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Bernhoft, A., primary, Clasen, P.-E., additional, Kristoffersen, A.B., additional, and Torp, M., additional
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- 2010
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26. Phylogenetic analyses of the Fusarium poae, Fusarium sporotrichioides and Fusarium langsethiae species complex based on partial sequences of the translation elongation factor-1 alpha gene
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Knutsen, A.K., primary, Torp, M., additional, and Holst-Jensen, A., additional
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- 2004
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27. An integrated taxonomic study of Fusarium langsethiae, Fusarium poae and Fusarium sporotrichioides based on the use of composite datasets
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Schmidt, H., primary, Adler, A., additional, Holst-Jensen, A., additional, Klemsdal, S.S., additional, Logrieco, A., additional, Mach, R.L., additional, Nirenberg, H.I., additional, Thrane, U., additional, Torp, M., additional, Vogel, R.F., additional, Yli-Mattila, T., additional, and Niessen, L., additional
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- 2004
- Full Text
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28. Botrytis fruit rot and microfungal populations on conventionally and organically produced strawberries
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Waipara, N.W., primary and Torp, M., additional
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- 2001
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29. Biodiversity of microfungi in soils plant roots and foods a comparison between organic and conventional agricultural ecosystems
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Waipara, N.W., primary and Torp, M., additional
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- 2000
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30. Toxicity and Occurrence of Fusarium species and Mycotoxins in Late Harvested and Overwintered Grain from Norway, 1993
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Langseth, W., primary, Kosiak, B., additional, Clasen, P.-E., additional, Torp, M., additional, and Gareis, M., additional
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- 1997
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31. Influence of agronomic and climatic factors on Fusarium infestation and mycotoxin contamination of cereals in Norway.
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Bernhoft, A., Torp, M., Clasen, P.-E., Løes, A.-K., and Kristoffersen, A.B.
- Abstract
A total of 602 samples of organically and conventionally grown barley, oats and wheat was collected at grain harvest during 2002–2004 in Norway. Organic and conventional samples were comparable pairs regarding cereal species, growing site and harvest time, and were analysed for Fusarium mould and mycotoxins. Agronomic and climatic factors explained 10–30% of the variation in Fusarium species and mycotoxins. Significantly lower Fusarium infestation and concentrations of important mycotoxins were found in the organic cereals. The mycotoxins deoxynivalenol (DON) and HT-2 toxin (HT-2) constitute the main risk for human and animal health in Norwegian cereals. The impacts of various agronomic and climatic factors on DON and HT-2 as well as on their main producers F. graminearum and F. langsethiae and on total Fusarium were tested by multivariate statistics. Crop rotation with non-cereals was found to reduce all investigated characteristics significantly – mycotoxin concentrations as well as various Fusarium infestations. No use of mineral fertilisers and herbicides was also found to decrease F. graminearum, whereas lodged fields increased the occurrence of this species. No use of herbicides was also found to decrease F. langsethiae, but for this species the occurrence was lower in lodged fields. Total Fusarium infestation was decreased with no use of fungicides or mineral fertilisers, and with crop rotation, as well as by using herbicides and increased by lodged fields. Clay and to some extent silty soils seemed to reduce F. graminearum in comparison with sandy soils. Concerning climate factors, low temperature before grain harvest was found to increase DON; and high air humidity before harvest to increase HT-2. F. graminearum was negatively correlated with precipitation in July but correlated with air humidity before harvest. F. langsethiae was correlated with temperature in July. Total Fusarium increased with increasing precipitation in July. Organic cereal farmers have fewer cereal intense rotations than conventional farmers. Further, organic farmers do not apply mineral fertiliser or pesticides (fungicides, herbicides or insecticides), and have less problem with lodged fields. The study showed that these agronomic factors were related to the infestation of Fusarium species and the concentration of mycotoxins. Hence, it is reasonable to conclude that farming system (organic versus conventional) impacts Fusarium infestation, and that organic management tends to reduce Fusarium and mycotoxins. However, Fusarium infestation and mycotoxin concentrations may be influenced by a range of factors not studied here, such as local topography and more local climate, as well as cereal species and variety. [ABSTRACT FROM PUBLISHER]
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- 2012
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32. Less Fusarium infestation and mycotoxin contamination in organic than in conventional cereals.
- Author
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Bernhoft, A., Clasen, P.-E., Kristoffersen, A.B., and Torp, M.
- Abstract
A total of 602 samples of cereals, consisting of organically and conventionally produced barley, oats and wheat, were collected at harvest during 2002–2004 in Norway. Organic and conventional cereals were sampled in comparable numbers regarding cereal species, localisation and harvest time, and analysed for Fusarium mould and mycotoxins. Fusarium infestation and mycotoxin content were dependent on cereal species and varied year-by-year. However, in all cereal species, Fusarium infestation and levels of important mycotoxins were significantly lower when grown organically than conventionally. Concerning the most toxic trichothecenes, HT-2 and T-2 toxin, lower concentrations were found in organic oats and barley. Wheat was not contaminated by HT-2 and T-2, but lower concentrations of deoxynivalenol (DON) and moniliformin (MON) were found when organically produced. For mycotoxins considered to constitute the main risk to humans and animals in Norwegian cereals, i.e. HT-2 in oats and DON in oats and wheat, the median figures (mean levels in brackets) were as follows: HT-2 in organic and conventional oats were <20 (80) and 62 (117) µg/kg, DON in organic and conventional oats were 24 (114) and 36 (426) µg/kg, and DON in organic and conventional wheat were 29 (86) and 51 (170) µg/kg, respectively. Concentrations of HT-2 and T-2 in the samples were strongly correlated (r = 0.94). Other mycotoxins did not show a significant correlation to each other. Both HT-2 and T-2 concentrations were significantly correlated with infestation of F. langsethiae (r = 0.65 and r = 0.60, respectively). Concentrations of DON were significantly correlated with F. graminearum infestation (r = 0.61). Furthermore, nivalenol (NIV) was significantly correlated with infestation of F. poae (r = 0.55) and MON with F. avenaceum (r = 0.37). As lower Fusarium infestation and mycotoxin levels were found in organic cereals, factors related to agricultural practice may reduce the risk of contamination with Fusarium mycotoxins. Studies of these issues will be presented separately. [ABSTRACT FROM AUTHOR]
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- 2010
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33. Toxicity and Occurrence of <em>Fusarium</em> species and Mycotoxins in Late Harvested and Overwintered Grain from Norway, 1993.
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Langseth, W., Kosiak, B., Clasen, P.-E., Torp, M., and Gareis, M.
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MICROBIAL toxins ,MYCOTOXINS ,FUNGAL metabolites ,GRAIN ,FUSARIUM oxysporum ,CELL culture - Abstract
Copyright of Journal of Phytopathology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 1997
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34. Detection and characterization of Campylobacter in air samples from poultry houses using shot-gun metagenomics - a pilot study.
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Haverkamp THA, Spilsberg B, Johannessen GS, Torp M, and Sekse C
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- Animals, Pilot Projects, Poultry microbiology, Feces microbiology, Housing, Animal, Real-Time Polymerase Chain Reaction methods, Campylobacter Infections veterinary, Campylobacter Infections microbiology, Campylobacter Infections diagnosis, Metagenomics methods, Chickens microbiology, Campylobacter isolation & purification, Campylobacter genetics, Campylobacter classification, Air Microbiology
- Abstract
Background: Foodborne pathogens such as Campylobacter jejuni are responsible for a large proportion of the gastrointestinal infections worldwide associated with poultry meat. Campylobacter spp. can be found in the chicken fecal microbiome and can contaminate poultry meat during the slaughter process. Commonly used sampling methods to detect Campylobacter spp. at poultry farms use fecal droppings or boot swabs in combination with conventional culture techniques or PCR. In this pilot study, we have used air filtering and filters spiked with mock communities in combination with shotgun metagenomics to detect Campylobacter and test the applicability of this approach for the detection and characterization of foodborne pathogens. To the best of our knowledge is this the first study that combines air filtering with shotgun metagenomic sequencing for detection and characterization of Campylobacter., Results: Analysis of air filters spiked with different levels of Campylobacter, into a background of mock or poultry house communities, indicated that we could detect as little as 200 colony forming units (CFU) Campylobacter per sample using our protocols. The results indicate that even with limited sequencing effort we could detect Campylobacter in the samples analysed in this study. We observed significant amounts of Campylobacter in real-life samples from poultry houses using both real-time PCR as well as shotgun metagenomics, suggesting that the flocks in both houses were infected with Campylobacter spp. Interestingly, in both houses we find diverse microbial communities present in the indoor air which reflect the fecal microbiome of poultry. Some of the identified genera such as Staphylococcus, Escherichia and Pseudomonas are known to contain opportunistic pathogenic species., Conclusions: These results show that air sampling of poultry houses in combination with shotgun metagenomics can detect and identify Campylobacter spp. present at low levels. This is important since early detection of Campylobacter enables measures to be put in place to ensure the safety of broiler products, animal health and public health. This approach has the potential to detect any pathogen present in poultry house air., (© 2024. The Author(s).)
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- 2024
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35. A Multicenter Proposal for a Fast Tool To Screen Biosecure Chicken Flocks for the Foodborne Pathogen Campylobacter .
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Hoorfar J, Koláčková I, Johannessen GS, Garofolo G, Marotta F, Wieczorek K, Osek J, Torp M, Spilsberg B, Sekse C, Thornval NR, and Karpíšková R
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- Animals, Campylobacter Infections diagnosis, Campylobacter Infections microbiology, Czech Republic, Denmark, Italy, Norway, Poland, Poultry Diseases microbiology, Campylobacter isolation & purification, Campylobacter Infections veterinary, Chickens, Poultry Diseases diagnosis
- Abstract
The present multicenter study aimed at assessing the performance of air sampling as a novel method for monitoring Campylobacter in biosecure poultry farms. We compared, using a harmonized procedure, the bacteriological isolation protocol (ISO 10272-1:2017) and a real-time PCR method used on air filter samples. Air samples and boot swabs were collected from 62 biosecure flocks from five European countries during the summer of 2019. For air filters, the frequency of PCR-positive findings was significantly higher ( n = 36; 58%) than that obtained with the cultivation methods ( P < 0.01; standardized residuals). The cultivation protocols (one with Bolton enrichment and one with Preston enrichment) were comparable to each other but returned fewer positive samples (0 to 8%). The association between type of sample and frequency of PCR-positive findings was statistically confirmed ( P < 0.01; Fisher´s exact test), although no culture-positive air filters were detected using direct plating. For the boot swabs, the highest number of positive samples were detected after enrichment in Preston broth ( n = 23; 37%), followed by direct plating after homogenization in Preston ( n = 21; 34%) or Bolton broth ( n = 20; 32%). It is noteworthy that the flocks in Norway, a country known to have low Campylobacter prevalence in biosecure chicken flocks, tested negative for Campylobacter by the new sensitive approach. In conclusion, air sampling combined with real-time PCR is proposed as a multipurpose, low-cost, and convenient screening method that can be up to four times faster and four times more sensitive than the current boot-swab testing scheme used for screening biosecure chicken production. IMPORTANCE Campylobacter bacteria are the cause of the vast majority of registered cases of foodborne illness in the industrialized world. In fact, the bacteria caused 246,571 registered cases of foodborne illness in 2018, which equates to 70% of all registered cases in Europe that year. An important tool to prevent campylobacters from making people sick is good data on where in the food chain the bacterium is present. The present study reports a new test method that quadruples the likelihood of identifying campylobacter-positive chicken flocks. It is important to identify campylobacter-positive flocks before they arrive at the slaughterhouse, because negative flocks can be slaughtered first in order to avoid cross-contamination along the production line., (Copyright © 2020 American Society for Microbiology.)
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- 2020
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36. Campylobacter in chicken - Critical parameters for international, multicentre evaluation of air sampling and detection methods.
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Johannessen GS, Garofolo G, Di Serafino G, Koláčková I, Karpíšková R, Wieczorek K, Osek J, Christensen J, Torp M, and Hoorfar J
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- Animals, Campylobacter genetics, Europe, Farms statistics & numerical data, Feces microbiology, Internationality, Pilot Projects, Poultry microbiology, Poultry Diseases microbiology, Poultry Diseases transmission, Air Microbiology standards, Campylobacter isolation & purification, Campylobacter Infections veterinary, Chickens microbiology, Poultry Diseases prevention & control
- Abstract
The present pilot study aimed at evaluating air sampling as a novel method for monitoring Campylobacter in poultry farms. We compared the bacteriological isolation of Campylobacter from boot swabs and air filter samples using ISO 10272-1:2017. A secondary aim was to evaluate the use of molecular methods, i.e. real time PCR, on the same sample set. Samples from 44 flocks from five European countries were collected, and included air samples, in parallel with boot swabs. Campylobacter spp. was isolated from seven of 44 boot swabs from three of five partners using the enrichment method. Two of these positive boot swab samples had corresponding positive air samples. Using enrichment, one positive air sample was negative in the corresponding boot swabs, but Campylobacter spp. was isolated from direct plating of the boot swab sample. One partner isolated Campylobacter spp. from six of 10 boot swabs using direct plating. Overall, 33 air filter samples were screened directly with PCR, returning 14 positive results. In conclusion, there was a lack of correspondence between results from analysis of boot swabs and air filters using ISO 10272-1:2017. In contrast, the combination of air filters and direct real-time PCR might be a way forward. Despite the use of the detailed ISO protocols, there were still sections that could be interpreted differently among laboratories. Air sampling may turn into a multi-purpose and low-cost sampling method that may be integrated into self-monitoring programs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest or commercial interest, and have all approved the manuscript for publication., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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37. Occurrence of and risk factors for extended-spectrum cephalosporin-resistant Enterobacteriaceae determined by sampling of all Norwegian broiler flocks during a six month period.
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Mo SS, Urdahl AM, Nesse LL, Slettemeås JS, Ramstad SN, Torp M, and Norström M
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- Animals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cephalosporins pharmacology, Cephalosporins therapeutic use, Enterobacteriaceae drug effects, Enterobacteriaceae physiology, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections microbiology, Enterobacteriaceae Infections veterinary, Norway epidemiology, Poultry Diseases drug therapy, Poultry Diseases microbiology, Risk Factors, Cephalosporin Resistance, Chickens microbiology, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections epidemiology, Poultry Diseases epidemiology
- Abstract
All broiler flocks reared and slaughtered in Norway from May-October 2016 (n = 2110) were screened for the presence of extended-spectrum cephalosporin (ESC) -resistant Enterobacteriaceae. Furthermore, we investigated possible risk factors for occurrence of such bacteria in broiler flocks. The odds of a flock being positive for ESC-resistant Enterobacteriaceae increased if the previous flock in the same house was positive, and if the flock was reared during September-October. However, we cannot exclude seasonal fluctuations in occurrence of ESC-resistant Enterobacteriaceae during the months November to April. The overall occurrence of ESC-resistant Enterobacteriaceae was 10.4%, and primarily linked to the presence of blaCMY (82.6%) in positive isolates. We describe the first findings of Escherichia coli with blaCTX-M-1, Klebsiella pneumoniae with both blaCTX-M-15 and blaSHV-12, and K. pneumoniae with blaCMY isolated from Norwegian broiler production. This study gives us a unique overview and estimate of the true occurrence of ESC-resistant Enterobacteriaceae in Norwegian broilers over a six-month period. To the best of our knowledge, this is the most comprehensive study performed on the occurrence of ESC-resistant Enterobacteriaceae in a broiler population., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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38. Glucose homeostasis in statin users-The LIFESTAT study.
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Morville T, Dohlmann T, Kuhlman AB, Monberg T, Torp M, Hartmann B, Holst JJ, Larsen S, Helge JW, and Dela F
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- Cross-Sectional Studies, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Male, Middle Aged, Prognosis, Cardiovascular Diseases prevention & control, Glucose Intolerance drug therapy, Homeostasis, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Insulin Resistance
- Abstract
Background: Statins are widely used to lower cholesterol concentrations in both primary and secondary prevention of cardiovascular disease. The treatment increases the risk of muscle pain (myalgia) and of type 2 diabetes. However, the underlying mechanisms remain disputed., Methods: We investigated whether statin induced myalgia is coupled to impaired glucose homeostasis using oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT), and the hyperinsulinemic euglycemic clamp. We performed a cross-sectional study of statin users without CVD (primary prevention) stratified into a statin myalgic (M; n = 25) and a non-myalgic (NM; n = 39) group as well as a control group (C; n = 20) consisting of non-statin users., Results: A reduction in the insulin secretion rate during the OGTT was observed in the myalgic group compared with the non-myalgic group (AUC ISR
OGTT , C: 1032 (683 - 1500); M: 922 (678 - 1091); NM: 1089 (933 - 1391) pmol·L-1 ·min (median with 25%-75% percentiles), but no other measurements indicated impaired β-cell function. We found no other differences between the three groups for other measurements in the OGTT, IVGTT, and euglycemic clamp. Muscle protein content of GLUT4 and hexokinase II was similar between the three groups., Conclusions: We conclude that statin users in primary prevention experiencing myalgia do not have impaired glucose homeostasis compared with other statin users or non-users. We consider this an important aspect in the dialogue between physician and patient regarding statin treatment and adverse effects., (© 2018 John Wiley & Sons, Ltd.)- Published
- 2019
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39. Encapsulated galanin-producing cells attenuate focal epileptic seizures in the hippocampus.
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Nikitidou L, Torp M, Fjord-Larsen L, Kusk P, Wahlberg LU, and Kokaia M
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- Animals, Cell Line, Disease Models, Animal, Drug Carriers administration & dosage, Electroencephalography, Enzyme-Linked Immunosorbent Assay, Epilepsies, Partial physiopathology, Galanin administration & dosage, Galanin analysis, Glycoside Hydrolases, Hippocampus chemistry, Hippocampus physiopathology, Humans, Male, Motor Cortex physiopathology, Rats, Rats, Sprague-Dawley, Cell Transplantation methods, Epilepsies, Partial drug therapy, Galanin therapeutic use, Hippocampus drug effects
- Abstract
Purpose: Encapsulated cell biodelivery (ECB) is a relatively safe approach, since the devices can be removed in the event of adverse effects. The main objectives of the present study were to evaluate whether ECB could be a viable alternative of cell therapy for epilepsy. We therefore developed a human cell line producing galanin, a neuropeptide that has been shown to exert inhibitory effects on seizures, most likely acting via decreasing glutamate release from excitatory synapses. To explore whether ECB of genetically modified galanin-producing human cell line could provide seizure-suppressant effects, and test possible translational prospect for clinical application, we implanted ECB devices bilaterally into the hippocampus of rats subjected to rapid kindling, a model for recurrent temporal lobe seizures., Methods: Two clones from a genetically modified human cell line secreting different levels of galanin were tested. Electroencephalography (EEG) recordings and stimulations were performed by electrodes implanted into the hippocampus at the same surgical session as ECB devices. One week after the surgery, rapid kindling stimulations were initiated., Key Findings: Enzyme-linked immunosorbent assay (ELISA) measurements prior to device implantation showed a release of galanin on average of 8.3 ng/mL/24 h per device for the low-releasing clone and 12.6 ng/mL/24 h per device for the high-releasing clone. High-releasing galanin-producing ECB devices moderately decreased stimulation-induced focal afterdischarge duration, whereas low-releasing ECB devices had no significant effect., Significance: Our study shows that galanin-releasing ECB devices moderately suppress focal stimulation-induced recurrent seizures. Despite this moderate effect, the study provides conceptual proof that ECB could be a viable alternative approach to cell therapy in humans, with the advantage that the treatment could be terminated by removing these devices from the brain. Thereby, this strategy provides a higher level of safety for future therapeutic applications, in which genetically modified human cell lines that are optimized to produce and release antiepileptic compounds could be clinically evaluated for their seizure-suppressant effects., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)
- Published
- 2014
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40. Congestive heart failure in rats is associated with increased collecting duct vasopressin sensitivity and vasopressin type 2 receptor reexternalization.
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Brønd L, Müllertz KM, Torp M, Nielsen J, Graebe M, Hadrup N, Nielsen S, Christensen S, and Jonassen TE
- Subjects
- Animals, Aquaporin 2 metabolism, Cyclic AMP metabolism, Disease Models, Animal, Female, Heart Failure physiopathology, Kidney Cortex metabolism, Kidney Tubules, Collecting metabolism, Rats, Rats, Wistar, Arginine Vasopressin metabolism, Heart Failure metabolism, Receptors, Vasopressin metabolism
- Abstract
A number of studies have shown that rats with congestive heart failure (CHF) have increased protein levels of the vasopressin (AVP)-regulated water channel aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in experimental CHF. The present study was aimed at investigating AVP signaling in rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal plasma AVP levels) induced by ligation of the left anterior descending coronary artery. Sham-operated rats were used as controls. Western blotting analyses revealed an increased abundance of AQP2 in renal cortex (+33 ± 9% of sham; P < 0.05) and in inner medulla (IM) (+54 ± 15% of sham; P < 0.05) in CHF rats compared with sham-operated controls. Dose-response studies on isolated collecting ducts (CDs) showed an increased accumulation of cAMP in response to AVP in CHF rats compared with controls. V2 receptor surface-binding studies in isolated IMCDs showed a marked and comparable AVP-induced V2 receptor internalization in response to AVP in both CHF and control rats. As expected V2 receptor surface binding remained low after AVP challenge in control rats. In contrast to this, V2 receptor surface binding returned to pre-AVP levels within 30 min in the CHF rats, indicating an obtained recycling ability of the V2 receptor in CHF. Together the results indicate the presence of an increased AVP sensitivity in the CDs from CHF rats, associated with an acquired recycling ability of the V2 receptor.
- Published
- 2013
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41. Performance of an herbivorous leaf beetle (Phratora vulgatissima) on Salix F2 hybrids: the importance of phenolics.
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Torp M, Lehrman A, Stenberg JA, Julkunen-Tiitto R, and Björkman C
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- Animals, Female, Genotype, Herbivory drug effects, Hybridization, Genetic, Luteolin chemistry, Luteolin pharmacology, Phenols pharmacology, Plant Leaves chemistry, Salicylates chemistry, Salicylates pharmacology, Salix genetics, Coleoptera physiology, Phenols chemistry, Salix chemistry
- Abstract
The genotype of the plant determines, through the expression of the phenotype, how well it is suited as food for herbivores. Since hybridization often results in profound genomic alterations with subsequent changes in phenotypic traits, it has the potential to significantly affect plant-herbivore interactions. In this study, we used a population of F2 hybrids that originated from a cross between a Salix viminalis and a Salix dasyclados genotype, which differed in both phenolic content and resistance to the herbivorous leaf beetle Phratora vulgatissima. We screened for plants that showed a great variability in leaf beetle performance (i.e., oviposition and survival). By correlating leaf phenolics to the response of the herbivores, we evaluated the importance of different phenolic compounds for Salix resistance to the targeted insect species. The performance of P. vulgatissima varied among the F2 hybrids, and two patterns of resistance emerged: leaf beetle oviposition was intermediate on the F2 hybrids compared to the parental genotypes, whereas leaf beetle survival demonstrated similarities to one of the parents. The findings indicate that these life history traits are controlled by different resistance mechanisms that are inherited differently in the hybrids. Salicylates and a methylated luteolin derivative seem to play major roles in hybrid resistance to Phratora vulgatissima. Synergistic effects of these compounds, as well as potential threshold concentrations, are plausible. In addition, we found considerable variation in both distributions and concentrations of different phenolics in the F2 hybrids. The phenolic profiles of parental genotypes and F2 hybrids differed significantly (e.g., novel compounds appeared in the hybrids) suggesting genomic alterations with subsequent changes in biosynthetic pathways in the hybrids.
- Published
- 2013
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42. Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke-induced striatal neurogenesis.
- Author
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Wang Z, Andrade N, Torp M, Wattananit S, Arvidsson A, Kokaia Z, Jørgensen JR, and Lindvall O
- Subjects
- Animals, Brain metabolism, Brain pathology, Brain physiopathology, Cell Survival, Chemotaxis, Corpus Striatum cytology, Corpus Striatum metabolism, Corpus Striatum pathology, Gene Expression Regulation, Male, Mice, Nerve Tissue Proteins administration & dosage, Nerve Tissue Proteins genetics, Neurons cytology, Rats, Rats, Wistar, Recombinant Proteins administration & dosage, Recombinant Proteins genetics, Recombinant Proteins metabolism, Stem Cells cytology, Stroke genetics, Stroke metabolism, Stroke pathology, Corpus Striatum physiopathology, Nerve Tissue Proteins metabolism, Neurogenesis, Neurons pathology, Stroke physiopathology
- Abstract
Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.
- Published
- 2012
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43. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo.
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Jørgensen JR, Fransson A, Fjord-Larsen L, Thompson LH, Houchins JP, Andrade N, Torp M, Kalkkinen N, Andersson E, Lindvall O, Ulfendahl M, Brunak S, Johansen TE, and Wahlberg LU
- Subjects
- Amino Acid Sequence, Animals, Animals, Newborn, Cell Survival drug effects, Cells, Cultured, Central Nervous System embryology, Central Nervous System metabolism, Cerebral Ventricles cytology, Chromatography, High Pressure Liquid, Cloning, Molecular, Culture Media, Conditioned chemistry, Deafness chemically induced, Deafness drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Doublecortin Domain Proteins, Embryo, Mammalian, Enzyme Inhibitors pharmacology, Female, Gene Expression Regulation, Developmental genetics, Guinea Pigs, Humans, In Vitro Techniques, Male, Mice, Microscopy, Electron, Scanning methods, Microtubule-Associated Proteins metabolism, Neomycin toxicity, Nerve Growth Factors genetics, Nerve Growth Factors metabolism, Nerve Growth Factors pharmacology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins pharmacology, Neural Stem Cells ultrastructure, Neurites ultrastructure, Neurons cytology, Neurons ultrastructure, Neuropeptides metabolism, Rats, Tandem Mass Spectrometry, Transfection methods, Cell Movement drug effects, Nerve Growth Factors therapeutic use, Neural Stem Cells drug effects, Neurites drug effects, Neurons drug effects, Spiral Ganglion cytology
- Abstract
Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor 1a. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2012
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44. Encapsulated cell-based biodelivery of meteorin is neuroprotective in the quinolinic acid rat model of neurodegenerative disease.
- Author
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Tornøe J, Torp M, Jørgensen JR, Emerich DF, Thanos C, Bintz B, Fjord-Larsen L, and Wahlberg LU
- Subjects
- Animals, Brain Tissue Transplantation methods, Capsules administration & dosage, Cell Line, Cytoprotection physiology, Humans, Huntington Disease chemically induced, Huntington Disease genetics, Male, Mice, Nerve Growth Factors administration & dosage, Nerve Growth Factors genetics, Nerve Growth Factors metabolism, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neuroprotective Agents administration & dosage, Neuroprotective Agents metabolism, Rats, Rats, Sprague-Dawley, Absorbable Implants standards, Cytoprotection drug effects, Disease Models, Animal, Huntington Disease drug therapy, Nerve Tissue Proteins administration & dosage, Quinolines toxicity
- Abstract
Purpose: Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity., Methods: Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats. Two weeks after implantation, QA was injected into the ipsilateral striatum followed by assessment of neurological performance two and four weeks after QA administration., Results: Implant-delivered Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death. Morphological analysis of the Meteorin-treated brains showed a markedly reduced striatal lesion size. The EC biodelivery devices produced stable or even increasing levels of Meteorin throughout the study over 6 weeks., Conclusions: Stereotactically implanted EC biodelivery devices releasing Meteorin could offer a feasible strategy in the treatment of neurological diseases with an excitotoxic component such as Huntington's disease. In a broader sense, the EC biodelivery technology is a promising therapeutic protein delivery platform for the treatment of a wide range of diseases of the central nervous system.
- Published
- 2012
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45. Lentiviral delivery of meteorin protects striatal neurons against excitotoxicity and reverses motor deficits in the quinolinic acid rat model.
- Author
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Jørgensen JR, Emerich DF, Thanos C, Thompson LH, Torp M, Bintz B, Fjord-Larsen L, Johansen TE, and Wahlberg LU
- Subjects
- Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Corpus Striatum pathology, Disease Models, Animal, Genetic Vectors genetics, Genetic Vectors therapeutic use, HEK293 Cells, Humans, Huntington Disease genetics, Huntington Disease metabolism, Male, Mice, Movement Disorders genetics, Movement Disorders metabolism, Nerve Tissue Proteins metabolism, Neurons pathology, Rats, Rats, Sprague-Dawley, Corpus Striatum metabolism, Genetic Therapy methods, Huntington Disease therapy, Lentivirus genetics, Movement Disorders therapy, Nerve Tissue Proteins genetics, Neurons metabolism
- Abstract
Meteorin is a newly discovered secreted protein involved in both glial and neuronal cell differentiation, as well as in cerebral angiogenesis during development; but effects in the adult nervous system are unknown. The growth factor-like properties and expression of Meteorin during the development of the nervous system raises the possibility that it might possess important neuroprotective or regenerative capabilities. This report is the first demonstration that Meteorin has potent neuroprotective effects in vivo. Lentiviral-mediated striatal delivery of Meteorin to rats two weeks prior to injections of quinolinic acid (QA) dramatically reduced the loss of striatal neurons. The cellular protection afforded by Meteorin was associated with normalization of neurological performance on spontaneous forelimb placing and cylinder behavioral tests and a complete protection against QA-induced weight loss. These benefits were comparable in magnitude to those obtained with lentiviral-mediated delivery of ciliary neurotrophic factor (CNTF), a protein with known neuroprotective properties in the same model system. In naive animals, endogenous levels of both Meteorin and CNTF were increased in glial cells in response to QA lesion indicating that Meteorin may exert its protective effects as part of the reactive gliosis cascade in the injured brain. In summary, these data demonstrate that Meteorin strongly protects striatal neurons and deserves additional evaluation as a novel therapeutic for the treatment of neurological disorders with an excitotoxic component such as Huntington's Disease., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2011
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46. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain.
- Author
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Fjord-Larsen L, Kusk P, Tornøe J, Juliusson B, Torp M, Bjarkam CR, Nielsen MS, Handberg A, Sørensen JC, and Wahlberg LU
- Subjects
- Animals, Capsules, Cell Line transplantation, Humans, Nerve Growth Factor administration & dosage, Retina cytology, Swine, Swine, Miniature, Time Factors, Alzheimer Disease drug therapy, Drug Delivery Systems, Nerve Growth Factor pharmacology, Neuroprotective Agents administration & dosage, Neuroprotective Agents therapeutic use, Prosencephalon drug effects
- Abstract
Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device, capable of local delivery of NGF. The clinical device, named NsG0202, houses an NGF-secreting cell line (NGC-0295), which is derived from a human retinal pigment epithelial (RPE) cell line, stably genetically modified to secrete NGF. Bioactivity and correct processing of NGF was confirmed in vitro. NsG0202 devices were implanted in the basal forebrain of Göttingen minipigs and the function and retrievability were evaluated after 7 weeks, 6 and 12 months. All devices were implanted and retrieved without associated complications. They were physically intact and contained a high number of viable and NGF-producing NGC-0295 cells after explantation. Increased NGF levels were detected in tissue surrounding the devices. The implants were well tolerated as determined by histopathological brain tissue analysis, blood analysis, and general health status of the pigs. The NsG0202 device represents a promising approach for treating the cognitive decline in AD patients.
- Published
- 2010
- Full Text
- View/download PDF
47. Characterization of Meteorin--an evolutionary conserved neurotrophic factor.
- Author
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Jørgensen JR, Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, and Wahlberg L
- Subjects
- Animals, Cells, Cultured, Female, Ganglia, Spinal cytology, Humans, Intercellular Signaling Peptides and Proteins genetics, Intercellular Signaling Peptides and Proteins metabolism, Mice, Nerve Tissue Proteins genetics, Neurons cytology, Neurons metabolism, Rats, Rats, Wistar, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Tissue Distribution, Biological Evolution, Nerve Growth Factors metabolism, Nerve Tissue Proteins metabolism
- Abstract
Growth factors control cellular growth, proliferation, and differentiation and may have therapeutic applications. In this study, we focus on Meteorin which is a member of a largely uncharacterized evolutionary conserved two-member growth factor family. Our analysis shows that Meteorin is expressed in the central nervous system both during development and in adult mice. Detailed immunohistological analysis of the adult mouse brain reveals that Meteorin is highly expressed in Bergmann glia and in a few discrete neuronal populations residing in the superior colliculus, the ocular motor nucleus, the raphe and pontine nuclei, and in various thalamic nuclei. In addition, low levels of Meteorin is found in astrocytes (S100beta+, OX42-) distributed ubiquitously throughout the brain. Meteorin was cloned and recombinant protein purified allowing N-terminal sequencing and mass spectrometric analysis showing that Meteorin is secreted as an unmodified monomer. This form is bioactive as it induces neurite outgrowth from dorsal root ganglions in vitro. Intrastriatal protein injection and lentiviral studies in vivo showed that Meteorin is a highly diffusible molecule in the brain and cellular uptake is apparent in specific populations which may carry the receptor. In summary, we provide a comprehensive expression analysis and have made and thoroughly validated molecular tools to help investigate the therapeutic potential of Meteorin.
- Published
- 2009
- Full Text
- View/download PDF
48. A review and integrative analysis of ancient holistic character medicine systems.
- Author
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Ventegodt S, Thegler S, Andreasen T, Struve F, Jacobsen S, Torp M, Aegedius H, Enevoldsen L, and Merrick J
- Subjects
- History, 15th Century, History, 16th Century, History, 17th Century, History, 18th Century, History, Ancient, History, Medieval, Holistic Health
- Abstract
The ancient holistic medical systems help the patient by balancing the "elements" of the human character. This work aims to understand the nature of these elements and the process of the physician balancing them. Using the concept of poly-ray cosmology we see that the medical systems from ancient India, China and Greek basically share the same inner structure and also the same logic of the treatment processes. We analyze the double concept of yin-yang, the Ayurvedic triadic concepts of Pitta, Kapha and Vata, the four elements of Hippocratic humoral medicine, and the five elements of Chinese medicine, and find that each of these conceptual frameworks make up a "theory" or model of the world that is a perfect wholeness, allowing the physician to interpret the world and his patient in order to identify the imbalances of his or her character that need to be treated. Independently of the system this can be a palliative treatment, if energies are only balanced in present time, or a causal cure if the physician is using the similarity principle to take his patient into regression back to the events in the personal history that originally created the imbalances (the traumas). To help the patient back to the traumas he is exposed to a small dose of the original harming stimulus; this can be an internal process like visualization supported by the therapist words, or an external process provoked by his actions. If the physician is balancing the elements without such a healing of the patient's existential core this can still momentarily help the patient by alleviating the symptoms, but it will not have a permanent effect.
- Published
- 2007
- Full Text
- View/download PDF
49. Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) in the treatment of experienced physical illness and chronic pain.
- Author
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Ventegodt S, Thegler S, Andreasen T, Struve F, Enevoldsen L, Bassaine L, Torp M, and Merrick J
- Subjects
- Combined Modality Therapy, Humans, Outcome Assessment, Health Care, Treatment Outcome, Chronic Disease therapy, Holistic Health, Mind-Body Therapies methods, Pain Management, Psychotherapy, Brief methods, Quality of Life
- Abstract
We investigated the treatment effect of psychodynamic short-term therapy complemented with bodywork on patients who presented with physical illness at the Research Clinic for Holistic Medicine in Copenhagen. Psychodynamic short-term therapy was complemented with bodywork (Marion Rosen) to help patients confront old emotional pain from childhood trauma(s). Patients were measured with a five-item quality of life and health questionnaire (QOL5), a one-item questionnaire of self-assessed quality of life (QOL1), and four questions on self-rated ability to love and to function sexually, socially, and at work (ability to sustain a full-time job). Most of the patients had chronic pain that could not be alleviated with drugs. Results showed that 31 patients with the experience of being severely physically ill (mostly from chronic pain), in spite of having consulted their own general practitioner, entered the study. The holistic approach and body therapy accelerated the therapy dramatically and no significant side effects were detected. After the intervention, 38.7% did not feel ill (1.73 < NNT < 4.58) (p = 0.05). Psychodynamic short-term therapy complemented with bodywork can help patients. When the patients responded to the therapy, the self-assessed mental health, relationship with partner, ability to work, self-assessed quality of life, relationships in general, measured QOL (with the validated questionnaire QOL5), and life's total state (mean of health, QOL and ability) were significantly improved, statistically and clinically. Most importantly, all aspects of life were improved simultaneously, due to induction of Antonovsky-salutogenesis. The patients received in average 20 sessions over 14 months at a cost of 1600 EURO. For the treatment responders, the treatment seemingly provided lasting benefits.
- Published
- 2007
- Full Text
- View/download PDF
50. Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) in the treatment of experienced impaired sexual functioning.
- Author
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Ventegodt S, Thegler S, Andreasen T, Struve F, Enevoldsen L, Bassaine L, Torp M, and Merrick J
- Subjects
- Combined Modality Therapy, Follow-Up Studies, Humans, Outcome Assessment, Health Care, Treatment Outcome, Holistic Health, Mind-Body Therapies methods, Psychotherapy methods, Quality of Life, Sexual Dysfunction, Physiological therapy, Sexual Dysfunctions, Psychological therapy
- Abstract
In this clinical follow-up study, we examined the effect of clinical holistic medicine (psychodynamic short-term therapy complemented with bodywork) on patients with poor self-assessed sexual functioning and found that this problem could be solved in 41.67% of the patients ((95% CI: 27.61-56.7%; 1.75 < NNT < 3.62, p = 0.05). The bodywork was inspired by the Marion Rosen method and helped the patients to confront painful emotions from childhood trauma(s), and thus accelerated and deepened the therapy. The goal of therapy was the healing of the whole life of the patient through Antonovsky-salutogenesis. In this process, rehabilitation of the character and purpose of life of the patient was essential, and assisted the patient to recover his or her sense of coherence (existential coherence). We conclude that clinical holistic medicine is the treatment of choice if the patient is ready to explore and assume responsibility for his or her existence (true self), and willing to struggle emotionally in the therapy to reach this important goal. When the patient heals existentially, quality of life, health, and ability to function in general are improved at the same time. The therapy was "mindful" in its focus on existential and spiritual issues. The patients received in average 14.8 sessions at the cost of 1,188 EURO.
- Published
- 2007
- Full Text
- View/download PDF
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