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- Campieri, M, et al.
(författare)
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Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group
- 1997
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 41:2, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- Background—The use of corticosteroids in active Crohn’s disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.Aims—To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn’s disease affecting the ileum and/or the ascending colon.Patients and methods—One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less.Results—After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p=0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p=0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p=0.0023).Conclusions—Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn’s disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.
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- Lingfors, H, et al.
(författare)
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Lifestyle changes after a health dialogue. Results from the Live for Life health promotion programme
- 2003
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Ingår i: Scandinavian Journal of Primary Health Care. ; 21, s. 248-252
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Tidskriftsartikel (refereegranskat)abstract
- Health Centre of Habo and Development Unit for Primary Health Care, Jönköping, Sweden. hans.lingfors@lj.se OBJECTIVE: To evaluate the effect of a health dialogue on lifestyle habits, and to relate the lifestyle changes to changes of biological risk markers for ischaemic heart disease. DESIGN: Cross-sectional study, intervention and follow-up. SETTING: The community of Habo, population 9500, located in Skaraborg, Sweden. PATIENTS: All 35-year-old inhabitants in Habo were invited to a health examination during a study period between 1989 and 1992. A community intervention programme was combined with a health examination consisting of a health dialogue with a specially trained nurse and use of a "health curve" as an educational tool. The effect of the health examination was examined by comparing baseline characteristics of participants in 1989-1992 with their follow-up data in 1993. RESULTS: Participants in the health dialogue who were re-examined reported lifestyle improvements including less smoking, decreased dietary fat intake and increased physical activity. Those who reported improved dietary intake and increased physical activity improved their biological risk markers correspondingly (body mass index, waist to hip ratio, serum cholesterol concentration). CONCLUSIONS: The combination of a community and an individually based health programme can be effective with respect to lifestyle variables and, in those improving their lifestyle, in biological risk markers. PMID: 14695077 [PubMed - indexed for MEDLINE]
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- Ye, L, et al.
(författare)
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Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.
- 2003
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Ingår i: Journal of Medicinal Chemistry. ; 24;46:9, s. 1580-8
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous thyroid receptor hormones 3,5,3',5'-tetraiodo-l-thyronine (T(4), 1) and 3,5,3'-triiodo-l-thyronine (T(3), 2) exert a significant effects on growth, development, and homeostasis in mammals. They regulate important genes in intestinal, skeletal, and cardiac muscles, the liver, and the central nervous system, influence overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood and overall sense of well being. The literature suggests many or most effects of thyroid hormones on the heart, in particular on the heart rate and rhythm, are mediated through the TRalpha(1) isoform, while most actions of the hormones on the liver and other tissues are mediated more through the TRbeta(1) isoform of the receptor. Some effects of thyroid hormones may be therapeutically useful in nonthyroid disorders if adverse effects can be minimized or eliminated. These potentially useful features include weight reduction for the treatment of obesity, cholesterol lowering for treating hyperlipidemia, amelioration of depression, and stimulation of bone formation in osteoporosis. Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism and, in particular, cardiovascular toxicity. Consequently, development of thyroid hormone receptor agonists that are selective for the beta-isoform could lead to safe therapies for these common disorders while avoiding cardiotoxicity. We describe here the synthesis and evaluation of a series of novel TR ligands, which are selective for TRbeta(1) over TRalpha(1). These ligands could potentially be useful for treatment of various disorders as outlined above. From a series of homologous R(1)-substituted carboxylic acid derivatives, increasing chain length was found to have a profound effect on affinity and selectivity in a radioreceptor binding assay for the human thyroid hormone receptors alpha(1) and beta(1) (TRalpha(1) and TRbeta(2)) as well as a reporter cell assay employing CHOK1-cells (Chinese hamster ovary cells) stably transfected with hTRalpha(1) or hTRbeta(1) and an alkaline phosphatase reporter-gene downstream thyroid response element (TRAFalpha(1) and TRAFbeta(1)). Affinity increases in the order formic, acetic, and propionic acid, while beta-selectivity is highest when the R(1) position is substituted with acetic acid. Within this series 3,5-dibromo-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (11a) and 3,5-dichloro-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (15) were found to reveal the most promising in vitro data based on isoform selectivity and were selected for further in vivo studies. The effect of 2, 11a, and 15 in a cholesterol-fed rat model was monitored including potencies for heart rate (ED(15)), cholesterol (ED(50)), and TSH (ED(50)). Potency for tachycardia was significantly reduced for the TRbeta selective compounds 11a and 15 compared with 2, while both 11a and 15 retained the cholesterol-lowering potency of 2. This left an approximately 10-fold therapeutic window between heart rate and cholesterol, which is consistent with the action of ligands that are approximately 10-fold more selective for TRbeta(1). We also report the X-ray crystallographic structures of the ligand binding domains of TRalpha and TRbeta in complex with 15. These structures reveal that the single amino acid difference in the ligand binding pocket (Ser277 in TRalpha or Asn331 in TRbeta) results in a slightly different hydrogen bonding pattern that may explain the increased beta-selectivity of 15.
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