The association between systolic blood pressure reduction during clonidine suppression testing and the decrease in plasma catecholamines and metanephrines.

Borderline isolated norepinephrine (NE) and normetanephrine (NMT) elevation is common among patients with suspected pheochromocytoma and paraganglioma (PPGL). The clonidine suppression test (CST) may help establish the etiology in these cases. Prolonged laboratory processing and/or paucity of reliable biochemical assays may limit the utility of CST. The aim of this study was to evaluate whether blood pressure (BP) reduction during CST is associated with alterations in plasma NMT/NE, thereby potentially providing an immediate indication of CST results. In this cross-sectional study, the authors included all consecutive patients with suspected PPGL who underwent CST from January 1, 2014, to December 31, 2019. Linear regression models were conducted to evaluate the association between BP reduction and decrease in plasma NMT/NE. The final analysis included 36 patients (17 males). The decrease in systolic BP (SBP) 90 minutes postclonidine was associated with a decrease in plasma NMT (R = 0.668, P = .025) and NE (R = 0.562, P = .005). A 40% decrease in NMT and NE correlated with a 9.74% and 7.16% decrease in SBP, respectively. Subgroup analyses demonstrated that the association between SBP reduction and the decrease in plasma NMT (R = 0.764, P = .046) and NE (R = 0.714, P = .003) strengthens among patients with hypertension and among those with diabetes mellitus (R = 0.974, P = .026 for NMT). In conclusion, SBP reduction during CST is associated with plasma NMT and NE decrease. Therefore, the decrease in SBP 90 minutes postclonidine may serve as an immediate complementary clinical tool for PPGL diagnosis.

Drosophila Past1 is involved in endocytosis and is required for germline development and survival of the adult fly.

Endocytosis, which is a key process in eukaryotic cells, has a central role in maintaining cellular homeostasis, nutrient uptake, development and downregulation of signal transduction. This complex process depends on several protein-protein interactions mediated by specific modules. One such module is the EH domain. The EH-domain-containing proteins comprise a family that includes four vertebrate members (EHD1-EHD4) and one Drosophila ortholog, Past1. We used Drosophila as a model to understand the physiological role of this family of proteins. We observed that the two predicted Past1 transcripts are differentially expressed both temporally and spatially during the life cycle of the fly. Endogenous Past1 as well as Past1A and Past1B, expressed from plasmids, were localized mainly to the membrane of Drosophila-derived cells. We generated mutants in the Past1 gene by excising a P-element inserted in it. The Past1 mutants reached adulthood but died precociously. They were temperature sensitive and infertile because of lesions in the reproductive system. Garland cells that originated from Past1 mutants exhibited a marked decrease in their ability to endocytose fluorescently labeled avidin. Genetic interaction was found between Past1 and members of the Notch signaling pathway, suggesting a role for Past1 in this developmentally crucial signaling pathway.