| 1. |
- Fredholm, BB, et al.
(författare)
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Consequences of eliminating adenosine A(1) receptors in mice
- 2003
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Ingår i: Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1). - : Wiley. - 1098-2299 .- 0272-4391. ; 58, s. 350-
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Konferensbidrag (refereegranskat)abstract
- The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
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| 2. |
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| 3. |
- Lovas, K, et al.
(författare)
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Replacement of dehydroepiandrosterone in adrenal failure : no benefit forsubjective health status and sexuality in a 9-month, randomized, parallelgroup clinical trial
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:3, s. 1112-
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Tidskriftsartikel (refereegranskat)abstract
- The physiological role of dehydroepiandrosterone (DHEA) is not well understood, but studies suggest positive effects on subjective health and bone metabolism. We have conducted a clinical trial with DHEA replacement in adrenal failure with the primary aim of evaluating effects on subjective health status and sexuality. Thirty-nine women with adrenal failure were randomized to 9 months of treatment with 25 mg DHEA (n = 19) or placebo (n = 20). Treatment effects were assessed by validated questionnaires of subjective health and sexuality. DHEA replacement yielded a wide variation of effects on the subjective health scales, which were not different from the effects of placebo. Almost all patients receiving DHEA obtained normal androgen levels. Eighty-nine percent of the patients receiving DHEA experienced side-effects, in particular increased sweat odor and scalp itching. DHEA replacement did not significantly change the levels of blood lipids, IGF-I, and markers of bone metabolism. In conclusion, we do not find evidence of beneficial effects of DHEA on subjective health status and sexuality in adrenal failure. However, DHEA may be beneficial for subgroups of patients with adrenal failure, but these remain to be identified. Premenopausal androgen levels can be restored with 25 mg DHEA daily in most female patients, but side-effects are frequent.
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| 4. |
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| 5. |
- Peterson, S, et al.
(författare)
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Assessing goitre prevalence - Reply
- 2000
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Ingår i: LANCET. - 0140-6736. ; 355:9219, s. 1996-1997
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Söderbergh, Annika, et al.
(författare)
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Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:2, s. 557-562
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.
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| 7. |
- Westermark, Gunilla, et al.
(författare)
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Islet amyloid development in a mouse strain lacking endogenous islet amyloid polypeptide (IAPP) but expressing human IAPP
- 2000
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Ingår i: Molecular Medicine. - 1076-1551 .- 1528-3658. ; 6:12, s. 998-1007
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several mouse strains expressing human islet amyloid polypeptide (IAPP) have been created to study development of islet amyloid and its impact on islet cell function. The tendency to form islet amyloid has varied strongly among these strains by factors that have not been elucidated. Because some beta cell granule components are known to inhibit IAPP fibril formation in vitro, we wanted to determine whether a mouse strain expressing human IAPP but lacking the nonamyloidogenic mouse IAPP is more prone to develop islet amyloidosis. Materials and Methods: Such a strain was created by cross-breeding a transgenic mouse strain and an IAPP null mouse strain. Results: when fed a fat-enriched diet, male mice expressing only human IAPP developed islet amyloid earlier and to a higher extent than did mice expressing both human and mouse IAPP. Supporting these results, we found that mouse IAPP dose-dependently inhibits formation of fibrils from human IAPP. Conclusions: Female mice did not develop amyloid deposits, although small extracellular amorphous IAPP deposits were found in some islets. When cultivated in vitro, amyloid deposits occurred within 10 days in islets from either male or female mice expressing only human IAPP. The study shows that formation of islet amyloid may be dependent on the environment, including the presence or absence of fibril inhibitors or promoters.
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