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  • 1
    Electronic Resource
    Electronic Resource
    Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains (2000)
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 12 (2000), S. 0 
    Details
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of propranolol and depot lanreotide SR on postprandial and circadian portal haemodynamics in cirrhosis (2003)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 18 (2003), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Long-acting somatostatin analogues have been suggested as an alternative to propranolol for the prevention of variceal rebleeding.Aim : To compare the effectiveness of lanreotide SR, a new depot formulation injected once-weekly, and propranolol in reducing circadian portal blood flow (PVF) and meal-stimulated hepatic venous pressure gradient (HVPG) in patients with liver cirrhosis.Methods : Patients were randomized to receive either lanreotide SR intramuscularly (30 mg once weekly, n = 12) or propranolol (n = 12) orally. Hemodynamic measurements were performed on day 0 and on day 21 after a 3-week period of drug administration, while patients received three standard oral liquid test meals. On each study day 27 PVF measurements were performed over 24 h and eight measurements of HVPG during the first postprandial period.Results : Propranolol was more effective than lanreotide SR in reducing baseline HVPG (−21.9 vs. −13.6%, P = 0.04) and meal-stimulated HVPG (−16.6 vs. −3.8%, P = 0.04). Propranolol reduced circadian PVF significantly by 9.3% (P = 0.03) but not lanreotide SR.Conclusions : Long-term treatment with propranolol reduced baseline and postprandial HVPG and circadian PVF, while lanreotide SR did not. The results of our study do not encourage clinical testing of lanreotide SR 30 mg for the prevention of variceal haemorrhage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2003.01682.x
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  • 3
    Electronic Resource
    Electronic Resource
    Does Octreotide Treatment Improve the Surgical Results of Macro-Adenomas in Acromegaly? A Randomized Study (1999)
    Springer
    Acta neurochirurgica 141 (1999), S. 399-405 
    Details
    ISSN: 0942-0940
    Keywords: Keywords: Acromegaly; macro-adenoma; octreotide; transsphenoidal surgery.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary  It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n=11, group A) and without (n=13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470±160 μg Octreotide for 16, 5±10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38, 9±34, 1 to 6, 8±4, 9 μg/l and from 2, 7±1 to 1, 7±0, 7 arbitrary units respectively. The adenoma-shrinkage from 5, 9±5, 8 to 4, 7±4, 9 cm3 missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of 〉50μ{\rm g/l}. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007010050316
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