18 results on '"Larsen LN"'
Search Results
2. Emerging Therapies for Acne Vulgaris.
- Author
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Trivedi MK, Bosanac SS, Sivamani RK, and Larsen LN
- Subjects
- Androgen Antagonists therapeutic use, Anti-Infective Agents therapeutic use, Biological Factors therapeutic use, Dermabrasion, Humans, Laser Therapy, Neurotransmitter Agents therapeutic use, Phytotherapy, Probiotics, Retinoids therapeutic use, Acne Vulgaris therapy
- Abstract
As we gain a greater understanding of acne pathogenesis, both new agents as well as new uses for established drugs are being considered for the treatment of acne vulgaris. Multiple clinical trials assessing new formulations or combinations of established acne treatments have been conducted, and novel uses of antimicrobials such as modified diallyl disulfide oxide and nitric oxide are being assessed in clinical trials. There are also a multitude of new therapies currently being studied that target the inflammatory cascade of acne pathogenesis, including sebosuppressive and anti-inflammatory phytochemicals, and small molecule inhibitors targeting sebaceous glands and enzymes, among others. Laser and light therapy is also being modified for the treatment of acne through combination methods with metal nanoshells and vacuum assistance. Probiotics have gained popularity in medicine as greater knowledge of the microbiome and its effects on multiple organ systems is being elucidated. Studies describing the positive effects of certain ammonia-oxidizing bacterial strains in the regulation of the skin's inflammatory response are ongoing. Therapies for acne are constantly evolving and current gold-standard acne therapy may be supplemented with novel treatment modalities in the near future.
- Published
- 2018
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3. Progestins and acne vulgaris: a review.
- Author
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Bosanac SS, Trivedi M, Clark AK, Sivamani RK, and Larsen LN
- Subjects
- Androgens adverse effects, Contraceptives, Oral therapeutic use, Drug Implants adverse effects, Humans, Intrauterine Devices, Medicated adverse effects, Acne Vulgaris chemically induced, Acne Vulgaris drug therapy, Progestins administration & dosage, Progestins adverse effects
- Abstract
The role of exogenous progestin in the development of acne is unclear. Progestins are known for their androgenic potential, but newer generations of progestins have low or anti-androgenic activity. This review will evaluate the association between progestins found in hormonal long-acting reversible contraceptives (intrauterine devices and subdermal implants) and acne, as well as the role of oral contraceptives in acne management. Our review demonstrates that the cause and effect relationship between progestins and acne is difficult to establish and future studies that seek to understand how progestins modulate acne are necessary.
- Published
- 2018
4. The use of hormonal agents in the treatment of acne.
- Author
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Hassoun LA, Chahal DS, Sivamani RK, and Larsen LN
- Subjects
- Administration, Oral, Cortodoxone analogs & derivatives, Cortodoxone therapeutic use, Cyproterone Acetate therapeutic use, Female, Finasteride therapeutic use, Flutamide therapeutic use, Hormones therapeutic use, Humans, Male, Meta-Analysis as Topic, Mineralocorticoid Receptor Antagonists therapeutic use, Propionates therapeutic use, Spironolactone therapeutic use, Treatment Outcome, Acne Vulgaris drug therapy, Contraceptive Agents therapeutic use, Dermatologic Agents therapeutic use, Hormones metabolism
- Abstract
Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies., (©2016 Frontline Medical Communications.)
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- 2016
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5. Daily intake of cod or salmon for 2 weeks decreases the 18:1n-9/18:0 ratio and serum triacylglycerols in healthy subjects.
- Author
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Telle-Hansen VH, Larsen LN, Høstmark AT, Molin M, Dahl L, Almendingen K, and Ulven SM
- Subjects
- Adult, Animals, Diet, Fatty Acid Synthases genetics, Fatty Acid Synthases metabolism, Female, Humans, Leukocytes, Mononuclear metabolism, Male, Phospholipids blood, Stearoyl-CoA Desaturase genetics, Stearoyl-CoA Desaturase metabolism, Fatty Acids, Omega-3 metabolism, Gadiformes, Salmon, Seafood, Triglycerides blood
- Abstract
Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced concentration of plasma triacylglycerols (TAG) but the mechanisms are not fully clarified. Stearoyl-CoA desaturase-1 (SCD1) activity, governing TAG synthesis, is affected by n-3 fatty acids. Peripheral blood mononuclear cells (PBMC) display expression of genes involved in lipid metabolism. The aim of the present study was to estimate whether intake of lean and fatty fish would influence n-3 fatty acids composition in plasma phospholipids (PL), serum TAG, 18:1n-9/18:0 ratio in plasma PL, as well as PBMC gene expression of SCD1 and fatty acid synthase (FAS). Healthy males and females (n = 30), aged 20-40, consumed either 150 g of cod, salmon, or potato (control) daily for 15 days. During intervention docosahexaenoic acid (DHA, 22:6n-3) increased in the cod group (P < 0.05), while TAG concentration decreased (P < 0.05). In the salmon group both eicosapentaenoic acid (EPA, 20:5n-3) and DHA increased (P < 0.05) whereas TAG concentration and the 18:1n-9/18:0 ratio decreased (P < 0.05). Reduction of the 18:1n-9/18:0 ratio was associated with a corresponding lowering of TAG (P < 0.05) and an increase in EPA and DHA (P < 0.05). The mRNA levels of SCD1 and FAS in PBMC were not significantly altered after intake of cod or salmon when compared with the control group. In conclusion, both lean and fatty fish may lower TAG, possibly by reducing the 18:1n-9/18:0 ratio related to allosteric inhibition of SCD1 activity, rather than by influencing the synthesis of enzyme protein.
- Published
- 2012
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6. Hydrochloric acid treatment of tunneled central venous catheter infections in children with cancer.
- Author
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Larsen LN, Malchau E, Kristensen B, and Schroeder H
- Subjects
- Anti-Bacterial Agents therapeutic use, Bacteremia etiology, Catheterization, Central Venous adverse effects, Child, Child, Preschool, Device Removal, Humans, Infant, Infant, Newborn, Bacteremia drug therapy, Catheter-Related Infections drug therapy, Catheters, Indwelling adverse effects, Hydrochloric Acid therapeutic use, Neoplasms complications
- Abstract
Background: Long-term tunneled central venous catheters (CVCs) are often the source of catheter-associated bloodstream infections (CABSIs), which may be difficult to eradicate and may lead to premature catheter removal., Procedure: This prospective controlled study used instillation of 2 M hydrochloric acid (HCl) as an adjuvant to the intravenous antibiotic treatment of children with bacteremia and compared the results with those from the immediate preceding period. The primary outcome variable was infection-related CVC removal within 100 days of bacteremia. Only patients with double lumen Hickman CVC with external tubings were included., Results: During a period of 36 months, 109 episodes of bacteremia were treated, 51 during the period where HCl was not used and 58 during the period where HCl was used. Forty-two out of 58 bacteremias were treated with HCl during the "HCl period." An intention-to-treat analysis showed that the median time to infection-related CVC removal was significantly longer during the HCl period compared with the non-HCl period (94 d vs. 12.5 d). At day 100 significantly more CVCs remained in place compared with the non-HCl period. Of the 42 CVCs treated with HCl, 2 had to be removed because of infection before day 30 and further 7 CVCs were removed before day 100. There was no difference in the occurrence of new bacteremias within the first 30 days of bacteremia in the 2 groups., Conclusion: HCl may successfully supplement intravenous antibiotics in the treatment of CABSI and contribute to CVC salvage.
- Published
- 2011
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7. Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP.
- Author
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Almendingen K, Larsen LN, Fausa O, Bratlie J, Høstmark AT, and Aabakken L
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- Adenomatous Polyposis Coli blood, Adenomatous Polyposis Coli drug therapy, Adolescent, Adult, Aged, Cyclooxygenase 1 chemistry, Cyclooxygenase 2 chemistry, Diet, Dinoprostone blood, Double-Blind Method, Duodenal Diseases metabolism, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Phospholipids blood, Placebos, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Young Adult, Adenomatous Polyposis Coli genetics, Cyclooxygenase 1 genetics, Cyclooxygenase 2 genetics, Cyclooxygenase 2 Inhibitors therapeutic use, Fatty Acids metabolism, Lactones therapeutic use, Sulfones therapeutic use
- Abstract
Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE(2) in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = -0.9; -0.1), and in duodenal lesions (P = 0.04, 95 CI % = -0.9; -0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE(2) levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP.
- Published
- 2010
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8. Infections during induction therapy for children with acute lymphoblastic leukemia. the role of sulfamethoxazole-trimethoprim (SMX-TMP) prophylaxis.
- Author
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Rungoe C, Malchau EL, Larsen LN, and Schroeder H
- Subjects
- Adolescent, Age Factors, Anti-Infective Agents, Bacteremia chemically induced, Child, Child, Preschool, Drug Evaluation, Female, Humans, Incidence, Infant, Male, Opportunistic Infections drug therapy, Retrospective Studies, Antibiotic Prophylaxis methods, Antineoplastic Combined Chemotherapy Protocols adverse effects, Opportunistic Infections prevention & control, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use
- Abstract
Background: Bacteremias are frequent during induction therapy for acute lymphoblastic leukemia (ALL) in children. Antibacterial prophylaxis therapy may thus be warranted. The purpose of this study was to analyze the rate of infections during induction therapy in two cohorts of children with ALL where one cohort received prophylactic sulfamethoxazole-trimethoprim (SMX-TMP)., Procedure: All infections were registered through a retrospective non-randomized review of medical records of 171 consecutive children newly diagnosed with ALL below 15 years of age at diagnosis. A total of 85 children treated from 1992 to 2000 did not receive SMX-TMP, whereas 86 children treated from 2000 to 2008 received SMX-TMP 20 mg/kg in one daily oral dose during induction therapy., Results: A total of 26% of all children had no febrile episodes during induction. Infections were more frequent in children below 5 years of age. Significantly fewer children receiving SMX-TMP developed fever (17% vs. 34%, P = 0.02) and bacteremia (20% vs. 45%, P = 0.0003). Especially children with non-high risk criteria had fewer infections when receiving prophylaxis. When adjusting for age, type of catheter, and SMX-TMP prophylaxis on the risk of bacteremia by a multiple Cox regression analysis, we found that age and prophylaxis, but not the type of catheter, were associated with a significantly reduced risk of bacteremia., Conclusion: Children with ALL receiving SMX-TMP prophylaxis during induction therapy experienced fewer febrile episodes, fewer days with fever demanding intravenous antibiotic treatment, and fewer episodes of bacteremia. Both SMX-TMP prophylaxis and age played significant independent roles for the occurrence of bacteremia., ((c) 2010 Wiley-Liss, Inc.)
- Published
- 2010
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9. Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients.
- Author
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Almendingen K, Høstmark AT, Larsen LN, Fausa O, Bratlie J, and Aabakken L
- Abstract
A few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids. We report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids, and relate this to the proportions of fatty acids and levels of cyclooxygenase mRNA expression in duodenal biopsies, levels of serum lipoproteins, and diet. In the ileostomy group separately (n = 12), the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies. Total serum-cholesterol was negatively correlated to the fecal content of saturates and monounsaturates. The fecal palmitoleic acid/palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.In the ileal-pouch-anal anastomosis group separately (n = 17), significant correlations were found between the fecal contents of oleic acid, linoleic acid, and alpha-linolenic acid, and the proportions of myristic acid, oleic acid and eicosaenoic acid in duodenal biopsies. Dietary monounsaturates were positively correlated to different fecal fatty acids. Future studies should focus on molecular mechanisms relevant to fatty acid metabolism, inflammation, and angiogenesis, in addition to nutrition.
- Published
- 2010
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10. [Tunnelled central venous catheters in children with cancer. Removal and duration].
- Author
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Schrøder H, Malchau E, Larsen LN, Bugge K, Olsen H, and Kamperis K
- Subjects
- Adolescent, Catheterization, Central Venous adverse effects, Child, Child, Preschool, Humans, Prospective Studies, Retrospective Studies, Time Factors, Catheterization, Central Venous instrumentation, Catheters, Indwelling adverse effects, Device Removal, Neoplasms therapy
- Abstract
Introduction: Most children with cancer have a tunnelled central venous catheter (CVC) inserted. The optimal type of CVC for children of all ages has not been identified. The purpose of this paper was to analyze factors correlated to the duration of catheterization of the first inserted CVC in children with cancer., Materials and Methods: All children with cancer who had their first CVC inserted between 01-01-2000 and 01-09-2006. Retrospective and prospective study of medical charts with respect to the type of CVC, age of the child at insertion, dates of insertion and removal, diagnosis and cause of CVC removal., Results: Between 01-01-2000 and 01-09-2006 155 double lumen Hickmans (2-Hick) and 86 double lumen Port-a-Caths (2-PaC) were inserted. The total number of CVC days was 27,192 for 2-Hicks and 20,623 for 2-PaCs. The median duration of catherization was significantly longer for 2-PaCs compared with 2-Hicks (200 versus 135 days). Compared with 2-PaCs significantly more 2-Hicks were removed non-electively because of either infections or mechanical complications. The survival of 2-Hicks was significantly shorter in children <5 years of age, but for 2-PaCs there were no correlation between the duration of catherization and the age of the child. 67% of the 2-PaCs were removed at the end of treatment compared with 32% of the 2-Hicks (P< 0,001, chi2 test). A multivariate analysis showed that the type of CVC (P<0,001) and the age of the child (P< 0,001) were independent factors for the duration of the catheterization., Conclusion: Port-a-Caths for children of all ages with cancer are associated with significantly fewer catheter removals due to complications.
- Published
- 2008
11. Effects of structural changes of fatty acids on lipid accumulation in adipocytes and primary hepatocytes.
- Author
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Granlund L, Larsen LN, Nebb HI, and Pedersen JI
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- 3T3 Cells, Adipocytes cytology, Animals, Biomarkers, Cells, Cultured, Gene Expression Regulation, Hepatocytes cytology, Homeostasis, Lipids chemistry, Male, Mice, Molecular Structure, RNA, Messenger metabolism, Rats, Rats, Wistar, Adipocytes metabolism, Fatty Acids chemistry, Fatty Acids metabolism, Hepatocytes metabolism, Lipid Metabolism
- Abstract
Conjugated linoleic acids (CLAs), tetradecylthioacetic acid (TTA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are all shown to differently affect lipid homeostasis. Additionally, previous studies have shown that introducing a methyl group in the molecule potentiates the hypolipidemic effect of EPA. The objective of this study was to determine how cis9,trans11 CLA, trans10,cis12 CLA, TTA, EPA and DHA affect lipid accumulation in 3T3-L1 adipocytes and in cultured primary rat hepatocytes, and to what extent changes in cis/trans configuration or introducing a methyl group in the molecules influence their way of affecting lipid accumulation in these cells. Our results show that trans10,cis12 CLA is highly specific in preventing lipid accumulation in adipocytes, and that small structural changes in the molecule (changing to trans/trans or introducing an alpha-methyl group) totally abolish this effect and up-regulate the expression levels of adipogenic marker genes towards control levels. Furthermore, all the fatty acids increased hepatic lipid accumulation, whereas the lipid content was normalized after adding an alpha-methyl group into the molecules. Taken together, our data demonstrate that the various fatty acids are highly specialized molecules, and that small structural changes markedly alter their way of affecting lipid accumulation in adipocytes and hepatocytes.
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- 2005
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12. Sulfur-substituted and alpha-methylated fatty acids as peroxisome proliferator-activated receptor activators.
- Author
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Larsen LN, Granlund L, Holmeide AK, Skattebøl L, Nebb HI, and Bremer J
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- Animals, COS Cells, Chlorocebus aethiops, Fatty Acids chemistry, Ligands, Methylation, PPAR alpha agonists, PPAR delta agonists, PPAR gamma agonists, Structure-Activity Relationship, Sulfur Compounds, Transfection, Fatty Acids pharmacology, Peroxisome Proliferator-Activated Receptors agonists
- Abstract
FA with varying chain lengths and an alpha-methyl group and/or a sulfur in the beta-position were tested as peroxisome proliferator-activated receptor (PPAR)alpha, -delta(beta), and -gamma ligands by transient transfection in COS-1 cells using chimeric receptor expression plasmids, containing cDNAs encoding the ligand-binding domain of PPARalpha, -delta, and -gamma. For PPARalpha, an increasing activation was found with increasing chain length of the sulfur-substituted FA up to C14-S acetic acid (tetradecylthioacetic acid = TTA). The derivatives were poor, and nonsignificant, activators of PPARdelta. For PPARgamma, activation increased with increasing chain length up to C16-S acetic acid. A methyl group was introduced in the alpha-position of palmitic acid, TTA, EPA, DHA, cis9,trans11 CLA, and trans10,cis12 CLA. An increased activation of PPARalpha was obtained for the alpha-methyl derivatives compared with the unmethylated FA. This increase also resulted in increased expression of the two PPARalpha target genes acyl-CoA oxidase and liver FA-binding protein for alpha-methyl TTA, alpha-methyl EPA, and alpha-methyl DHA. Decreased or altered metabolism of these derivatives in the cells cannot be excluded. In conclusion, saturated FA with sulfur in the beta-position and increasing carbon chain length from C9-S acetic acid to C14-S acetic acid have increasing effects as activators of PPARalpha and -gamma in transfection assays. Furthermore, alpha-methyl FA derivatives of a saturated natural FA (palmitic acid), a sulfur-substituted FA (TTA), and PUFA (EPA, DHA, c9,t11 CLA, and t10,c12 CLA) are stronger PPARalpha activators than the unmethylated compounds.
- Published
- 2005
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13. Absorption of very-long-chain saturated fatty acids in totally hydrogenated fish oil.
- Author
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Granlund L, Larsen LN, Christiansen EN, and Pedersen JI
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- Analysis of Variance, Animals, Cholesterol blood, Cholesterol metabolism, Feces chemistry, Fish Oils administration & dosage, Intestinal Absorption physiology, Male, Rats, Triglycerides blood, Triglycerides metabolism, Fatty Acids metabolism, Fish Oils metabolism
- Abstract
Partially hydrogenated fish oil (PHFO) contains a high amount of trans fatty acids (TFA). Total hydrogenation results in a minimal amount of TFA, but a high content of very-long-chain saturated fatty acids (VLCSFA). Absorption and metabolism of VLCSFA from totally hydrogenated fish oil (THFO) were studied in rats. Groups of eight rats were fed one of four diets containing 40 g soyabean oil (SBO)/kg (low-fat diet), 150 g SBO/kg (SBO diet), 40 g PHFO/kg (PHFO diet) or 40 g THFO/kg (THFO diet) for 4 weeks. A lower absorption coefficient of the fat content was found in the THFO group (61 %) compared with the other groups (PHFO 95 %, SBO 99 %, low fat 98 %; which was mainly due to reduced absorption of VLCSFA. A reduced weight gain was found for the THFO group compared with the other groups, but this was only significant when compared with the SBO group Faecal fat excretion (dry weight) was markedly increased in the THFO group (47 %), which was 2.4, 4.8 and 8.3 times higher compared with the groups fed PHFO, SBO and low-fat diets respectively. Serum total cholesterol was reduced for the PHFO and THFO groups whereas serum triacylglycerol was increased for the PHFO group compared with the other groups Animals fed THFO diet had an increased content of 20:0 and 22:0 in the serum triacylglycerol fraction whereas only 20:0 was increased in the serum phospholipid fraction The low absorption coefficient of THFO must be considered if this fat is to be used for consumption by animals or man.
- Published
- 2000
14. Alpha- and beta- alkyl-substituted eicosapentaenoic acids: incorporation into phospholipids and effects on prostaglandin H synthase and 5-lipoxygenase.
- Author
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Larsen LN, Bremer J, Flock S, and Skattebøl L
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- Animals, Arachidonic Acid biosynthesis, Cell Line, Docosahexaenoic Acids metabolism, Eicosapentaenoic Acid metabolism, Kinetics, Linoleic Acid metabolism, Liver drug effects, Liver metabolism, Rats, Structure-Activity Relationship, Thromboxane B2 biosynthesis, Triglycerides biosynthesis, Arachidonate 5-Lipoxygenase metabolism, Eicosapentaenoic Acid analogs & derivatives, Eicosapentaenoic Acid pharmacology, Phospholipids biosynthesis, Prostaglandin-Endoperoxide Synthases metabolism
- Abstract
Alpha-ethyl-, alpha-methyl- and beta-methyl eicosapentaenoic acid (EPA) were prepared and their incorporation into cell lipids and effects on eicosanoid synthesis compared with EPA and docosahexaenoic acid (DHA). alpha- and beta-methyl EPA were incorporated into hepatocyte triacylglycerols as efficiently as EPA, whereas lesser amounts were found in phospholipids. alpha-ethyl EPA was not incorporated into phospholipids but small amounts were detected in triacylglycerol. All derivatives inhibited the synthesis of arachidonic acid, although less efficiently than EPA and DHA. The derivatives were poor substrates of prostaglandin H (PGH) synthase and 5-lipoxygenase, and they all inactivated PGH synthase. In isolated platelets, alpha-methyl EPA was a stronger inhibitor of TxB2 production than EPA, alpha-ethyl- and beta-methyl EPA. All derivatives were stronger inducers of peroxisomal beta-oxidation than EPA and DHA. This increased induction probably is a consequence of the blocked mitochondrial beta-oxidation of the derivatives.
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- 1998
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15. Polyunsaturated thia- and oxa-fatty acids: incorporation into cell-lipids and their effects on arachidonic acid- and eicosanoid synthesis.
- Author
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Larsen LN, Hørvik K, Sørensen HI, and Bremer J
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- Acyl-CoA Oxidase, Animals, Arachidonate 5-Lipoxygenase metabolism, Cyclooxygenase Inhibitors pharmacology, Fatty Acids, Unsaturated chemistry, Fatty Acids, Unsaturated pharmacology, Liver Neoplasms, Experimental, Macrophages, Peritoneal, Male, Mice, Microbodies enzymology, Oxidoreductases biosynthesis, Prostaglandin-Endoperoxide Synthases metabolism, Rats, Rats, Wistar, Triglycerides metabolism, Tumor Cells, Cultured, gamma-Linolenic Acid biosynthesis, Arachidonic Acid biosynthesis, Eicosanoids biosynthesis, Fatty Acids, Unsaturated metabolism, Lipid Metabolism
- Abstract
EPA, DHA, C15SCH2COOH (n-3), C15SCH2COOH (n-6) and C18SCH2COOH (n-3) are extensively incorporated into phospholipids and triacylglycerol in rat hepatocytes after 24 h incubation with 80 microM fatty acid/derivative. Only traces of polyunsaturated 3-oxa fatty acids (C15OCH2COOH, C18OCH2COOH) were incorporated. C15-S-butyric acid (n-3) is a stronger inhibitor of delta6-desaturase in rat liver-microsomes than C15SCH2COOH (n-3), C15-S-propionic acid (n-3), EPA and DHA. It inhibits delta5-desaturase in a similar manner to EPA and DHA. Arachidonic acid and C15SCH2COOH, (n-6) are better substrates for PGH-synthase than EPA and C15SCH2COOH, (n-3), showing the inhibitory effect of the n-3 bond. The n-3 polyunsaturated fatty acids, including the sulfur-substituted fatty acid derivatives, are poor substrates for PGH-synthase. However, they inactivate the PGH-synthase activity at least as efficiently as arachidonic acid. C15SCH2COOH (n-3), C15S(CH2)2COOH (n-3) and C18SCH2COOH (n-3) induce peroxisomal beta-oxidation more than EPA and DHA.
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- 1997
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16. Heneicosapentaenoate (21:5n-3): its incorporation into lipids and its effects on arachidonic acid and eicosanoid synthesis.
- Author
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Larsen LN, Høvik K, Bremer J, Holm KH, Myhren F, and Børretzen B
- Subjects
- Animals, Arachidonate 5-Lipoxygenase metabolism, Delta-5 Fatty Acid Desaturase, Docosahexaenoic Acids metabolism, Eicosapentaenoic Acid metabolism, Fatty Acid Desaturases antagonists & inhibitors, Fatty Acid Desaturases metabolism, Linoleoyl-CoA Desaturase, Liver cytology, Liver metabolism, Liver Neoplasms, Experimental metabolism, Macrophages, Peritoneal cytology, Macrophages, Peritoneal metabolism, Male, Mice, Phospholipids metabolism, Prostaglandin-Endoperoxide Synthases metabolism, Rats, Substrate Specificity, Triglycerides metabolism, Arachidonic Acid biosynthesis, Eicosanoids biosynthesis, Fatty Acids, Omega-3 metabolism, Lipid Metabolism
- Abstract
6,9,12,15,18-Heneicosapentaenoic acid (21:5n-3) (HPA), present in small amounts in fish oils, has been prepared by chemical elongation of eicosapentaenoic acid (EPA) and its biological properties compared with EPA and docosahexaenoic acid (DHA). All the double bonds of HPA are displaced one carbon away from the carboxyl group when compared to EPA. HPA is incorporated into phospholipids and into triacylglycerol in cell culture to a similar extent as EPA and DHA. HPA is a stronger inhibitor of the conversion of alpha-linoleic acid and dihomo-gamma-linolenic acid to arachidonic acid (AA) in hepatoma cells than are EPA, DHA, and AA. HPA is a poor substrate for prostaglandin H synthase and for 5-lipoxygenase, but it inactivates prostaglandin H synthase as rapidly as do AA, EPA, and DHA. HPA inhibits thromboxane synthesis in isolated platelets as efficiently as EPA. EPA, HPA, and DHA are all weak inducers of acyl-CoA oxidase in hepatoma cells. Therefore, since fish oils contain only small amounts of HPA, it is unlikely that this fatty acid is of particular significance for the biological effects of these oils, possibly with the exception that it is a strong inhibitor of AA synthesis.
- Published
- 1997
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17. Thia fatty acids, metabolism and metabolic effects.
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Skrede S, Sørensen HN, Larsen LN, Steineger HH, Høvik K, Spydevold OS, Horn R, and Bremer J
- Subjects
- Acyl-CoA Dehydrogenase, Long-Chain metabolism, Acyl-CoA Oxidase, Animals, Enzyme Inhibitors pharmacology, Fatty Acids chemistry, Fatty Acids pharmacology, Humans, Lipid Metabolism, Liver drug effects, Liver metabolism, Oxidation-Reduction, Oxidoreductases metabolism, Phospholipids metabolism, Stearoyl-CoA Desaturase, Substrate Specificity, Sulfur chemistry, Triglycerides metabolism, Fatty Acid Desaturases, Fatty Acids metabolism
- Abstract
(1) The chemical properties of thia fatty acids are similar to normal fatty acids, but their metabolism (see below: points 2-6) and metabolic effects (see below: points 7-15) differ greatly from these and are dependent upon the position of the sulfur atom. (2) Long-chain thia fatty acids and alkylthioacrylic acids are activated to their CoA esters in endoplasmatic reticulum. (3) 3-Thia fatty acids cannot be beta-oxidized. They are metabolized by extramitochondrial omega-oxidation and sulfur oxidation in the endoplasmatic reticulum followed by peroxisomal beta-oxidation to short sulfoxy dicarboxylic acids. (4) 4-Thia fatty acids are beta-oxidized mainly in mitochondria to alkylthioacryloyl-CoA esters which accumulate and are slowly converted to 2-hydroxy-4-thia acyl-CoA which splits spontaneously to an alkylthiol and malonic acid semialdehyde-CoA ester. The latter presumably is hydrolyzed and metabolized to acetyl-CoA and CO2. (5) Both 3- and 4-thiastearic acid are desaturated to the corresponding thia oleic acids. (6) Long-chain 3- and 4-thia fatty acids are incorporated into phospholipids in vivo, particularly in heart, and in hepatocytes and other cells in culture. (7) Long-chain 3-thia fatty acids change the fatty acid composition of the phospholipids: in heart, the content of n-3 fatty acids increases and n-6 fatty acids decreases. (8) 3-Thia fatty acids increase fatty acid oxidation in liver through inhibition of malonyl-CoA synthesis, activation of CPT I, and induction of CPT-II and enzymes of peroxisomal beta-oxidation. Activation of fatty acid oxidation is the key to the hypolipidemic effect of 3-thia fatty acids. Also other lipid metabolizing enzymes are induced. (9) Fatty acid- and cholesterol synthesis is inhibited in hepatocytes. (10) The nuclear receptors PPAR alpha and RXR alpha are induced by 3-thia fatty acids. (11) The induction of enzymes and of PPAR alpha and RXR alpha are increased by dexamethasone and counteracted by insulin. (12) 4-Thia fatty acids inhibit fatty acid oxidation and induce fatty liver in vivo. The inhibition presumably is explained by accumulation of alkylthioacryloyl-CoA in the mitochondria. This metabolite is a strong inhibitor of CPT-II. (13) Alkylthioacrylic acids inhibits both fatty acid oxidation and esterification. Inhibition of esterification presumably follows accumulation of extramitochondrial alkylthioacryloyl-CoA, an inhibitor of microsomal glycerophosphate acyltransferase. (14) 9-Thia stearate is a strong inhibitor of the delta 9-desaturase in liver and 10-thia stearate of dihydrosterculic acid synthesis in trypanosomes. (15) Some attempts to develop thia fatty acids as drugs are also reviewed.
- Published
- 1997
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18. Peroxidative oxidation of leuco-dichlorofluorescein by prostaglandin H synthase in prostaglandin biosynthesis from polyunsaturated fatty acids.
- Author
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Larsen LN, Dahl E, and Bremer J
- Subjects
- Animals, Cyclooxygenase Inhibitors pharmacology, Horseradish Peroxidase, Hydrogen Peroxide, Hydrogen-Ion Concentration, Indomethacin pharmacology, Male, Oxidation-Reduction, Phenol, Phenols pharmacology, Prostaglandin-Endoperoxide Synthases chemistry, Serum Albumin, Bovine pharmacology, Sheep, Spectrophotometry, Substrate Specificity, Fatty Acids, Unsaturated metabolism, Fluoresceins chemistry, Prostaglandin-Endoperoxide Synthases metabolism, Prostaglandins biosynthesis
- Abstract
Prostaglandin H synthase can oxidize arachidonic acid with leuco-dichlorofluorescein as reducing cosubstrate. Addition of 0.5 mM phenol increases the oxidation of leuco-dichlorofluorescein to dichlorofluorescein 5-fold, probably by acting as a cyclic intermediate in the oxidation. Tetramethyl-p-phenylenediamine is also oxidized as cosubstrate. Its oxidation is not influenced by phenol. A stoichiometry of close to one mole of tetramethyl-p-phenylenediamine or leuco-dichlorofluorescein consumed per mole of arachidonic acid was found in the initial phase of the reaction. In the presence of phenol + leuco-dichlorofluorescein, the oxidation rate of arachidonic acid is about 40% lower than with phenol alone as cosubstrate. Since dichlorofluorescein has a molar extinction coefficient of 91 . 10(3) at 502 nm, the oxidation of less than 1 microM leuco-dichlorofluorescein can be detected spectrophotometrically. The rate of extinction change with leuco-dichlorofluorescein (at 502 nm) is about 4-fold more rapid than with tetramethyl-p-phenylenediamine (at 611 nm). With this spectrophotometric assay we have confirmed that arachidonic acid, linolenic acid, adrenic acid, gamma-linolenic acid, eicosapentaenoic acid, are substrates for prostaglandin H synthase with decreasing reaction rates in the mentioned order. The same order of reaction rates were found when oxygen consumption was measured. The assay also shows that docosahexaenoic acid is substrate for the enzyme. The reaction rate of the enzyme evidently is decreased both by a n-3 double bond and by deviation from a 20 carbon chain length of the fatty acid substrate.
- Published
- 1996
- Full Text
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