Circulating aryl hydrocarbon receptor-interacting protein (AIP) is independent of GH secretion.

Background: Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients. Subjects and methods: Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP. Results: Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT. Conclusions: Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.Serbian Ministry of Science (Project number 175033)MS from Society for Endocrinology (Practical Skills Grant)MS from Society for Endocrinology (Practical Skills Grant)British Society for Neuroendocrinology (Research Visit Grant)European Society of Endocrinology (Short Term Fellowship)Wellcome Clinical Training Fellowship (Grant no 097970/Z/11/Z)

Second generation of Fucose-based DC-SIGN ligands : affinity improvement and specificity versus Langerin

DC-SIGN and Langerin are two C-type lectins involved in the initial steps of HIV infections: the former acts as a viral attachment factor and facilitates viral invasion of the immune system, the latter has a protective effect. Potential antiviral compounds targeted against DC-SIGN were synthesized using a common fucosylamide anchor. Their DC-SIGN affinity was tested by SPR and found to be similar to that of the natural ligand Lewis-X (Le X). The compounds were also found to be selective for DC-SIGN and to interact only weakly with Langerin. These molecules are potentially useful therapeutic tools against sexually transmitted HIV infection

Effect of 12 Months of Recombinant Human Growth Hormone Replacement Therapy on Insulin Sensitivity in GH-Deficient Adults as Determined by Different Methods

BACKGROUND: Controversial results have been obtained in measuring insulin sensitivity (SI) during recombinant human growth hormone (rhGH) treatment in adult growth hormone deficient (GH-deficient) patients. AIMS: The aim of our study was to estimate SI before and during treatment using three different methods for quantifying insulin sensitivity in GH-deficient adults treated with rhGH. SETTINGS AND DESIGN: Twenty-one GH-deficient adults were treated with rhGH during 12 months. SI was estimated using Minimal model analysis, Homeostatic Model of Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) before and after 3, 6, 9 and 12 months of rhGH therapy. PATIENTS AND METHODS: Oral Glucose Tolerance Test (OGTT) and Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) were performed in each patient at respective time intervals. QUICKI and HOMA were calculated using basal values of glucose and insulin from FSIGT. Minimal model computer analysis was calculated from glucose and insulin data obtained during FSIGT. STATISTICAL ANALYSIS: Area under the curve for glucose, insulin and C-peptide were calculated using trapezoidal rule from OGTT data. Differences and correlations were tested using ANOVA for repeated measures, Wilcoxon's matched-paired test, paired t-test, Pearson's correlation and Bland Altman plot. RESULTS: There were no significant changes in SI using Minimal model analysis and QUICKI during rhGH treatment. On the contrary, HOMA analysis indicated significant deterioration in SI after 12 months of therapy. CONCLUSION: Our study did not demonstrate any changes in SI using Minimal model and QUICKI analysis, while there was significant increase in insulin resistance using HOMA model. We suggest that the choice of method for the determination of SI may influence the interpretation of results concerning the effect of rhGH therapy on SI in GH-deficient adults

Effect of 12 months of recombinant human growth hormone replacement therapy on insulin sensitivity in GH-deficient adults as determined by different methods

BACKGROUND: Controversial results have been obtained in measuring insulin sensitivity (SI) during recombinant human growth hormone (rhGH) treatment in adult growth hormone deficient (GH-deficient) patients. AIMS: The aim of our study was to estimate SI before and during treatment using three different methods for quantifying insulin sensitivity in GHdeficient adults treated with rhGH. SETTINGS AND DESIGN: Twenty-one GH-deficient adults were treated with rhGH during 12 months. SI was estimated using Minimal model analysis, Homeostatic Model of Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) before and after 3, 6, 9 and 12 months of rhGH therapy. PATIENTS AND METHODS: Oral Glucose Tolerance Test (OGTT) and Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) were performed in each patient at respective time intervals. QUICKI and HOMA were calculated using basal values of glucose and insulin from FSIGT. Minimal model computer analysis was calculated from glucose and insulin data obtained during FSIGT. STATISTICAL ANALYSIS: Area under the curve for glucose, insulin and C-peptide were calculated using trapezoidal rule from OGTT data. Differences and correlations were tested using ANOVA for repeated measures, Wilcoxon’s matched-paired test, paired t-test, Pearson’s correlation and Bland Altman plot. RESULTS: There were no significant changes in SI using Minimal model analysis and QUICKI during rhGH treatment. On the contrary, HOMA analysis indicated significant deterioration in SI after 12 months of therapy. CONCLUSION: Our study did not demonstrate any changes in SI using Minimal model and QUICKI analysis, while there was significant increase in insulin resistance using HOMA model. We suggest that the choice of method for the determination of SI may influence the interpretation of results concerning the effect of rhGH therapy on SI in GH-deficient adults

Clinical usefulness of ^99mTc-HYNIC-TOC, ^99mTc(V)-DMSA, and ^99mTc-MIBI SPECT in the evaluation of pituitary adenomas

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Background The aim of this study was to evaluate the behavioral uptake and ability to diagnose pituitary adenoma (PA) using tumor-seeking radiopharmaceuticals, and to provide a semiquantitative analysis of tracer uptake in the pituitary region. Patients and methods The study included 33 (13 hormonally active and 20 nonfunctioning) patients with PA and 45 control participants without pituitary involvement. All patients (n=78) underwent single photon emission computed tomography (SPECT) imaging with technetium-99m-labeled hydrazinonicotinyl-tyr 3 -octreotide (99mTc-HYNIC-TOC), dimercaptosuccinic acid (99mTc(V)-DMSA) and hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI). A semiquantitative analysis of abnormal uptake was carried out by drawing identical regions of interest over the pituitary area and the normal brain on one transverse section that shows the lesion most clearly. The pituitary uptake to normal brain uptake (P/B) ratio was calculated in all cases. Results The result of this study confirms that the SPECT semiquantitative method, with all three tracers, showed statistically significant differences between the PA group and the controls. However, 99mTc-HYNIC-TOC scintigraphy could have the highest diagnostic yield because of the smallest overlap between the P/B ratios between adenoma versus nonadenoma participants (the receiver operating characteristic curve P/B ratio cut-off value was 13.08). In addition, only 99mTc-MIBI SPECT have the diagnostic potential to detect secreting PAs, with statistically significant differences between groups (P<0.001), with an receiver operating characteristic curve P/B ratio cut-off value of 16.72. Conclusion A semiquantitative analysis of increased focal tracer uptake in the sellar area showed that 99mTc-HYNIC-TOC is a highly sensitive and reliable tumor-seeking agent for detecting PA, whereas 99mTc-MIBI SPECT is a highly sensitive and specific method in differentiating hormone-secreting pituitary tumor