Protocol for Clinical GLP-1 Receptor PET/CT Imaging with [68Ga]Ga-NODAGA-Exendin-4.

Imaging with radiolabeled exendin enables detection and characterization of glucagon-like peptide 1 receptors (GLP-1Rs) in vivo with high specificity. The novel radiotracer [68Ga]Ga-NODAGA-exendin-4 forms a stable complex after a simple and fast labeling procedure. Beta-cell mass in the islets of Langerhans can be visualized using [68Ga]Ga-NODAGA-exendin-4, which is promising for research into diabetes mellitus (DM) pathophysiology. Furthermore, this radiotracer enables very sensitive detection of insulinomas, resulting from vast overexpression of GLP-1Rs, and seems promising for the detection of focal lesions in congenital hyperinsulinism (CHI). Here, we describe the procedures involved in [68Ga]Ga-NODAGA-exendin-4 positron emission tomography (PET)/computed tomography (CT) imaging including the radiolabeling of the NODAGA-exendin conjugate with 68Ga, quality controls, and PET/CT.

Comparison of three different pelvic circumferential compression devices: a biomechanical cadaver study.

BACKGROUND: Pelvic circumferential compression devices are designed to stabilize the pelvic ring and reduce the volume of the pelvis following trauma. It is uncertain whether pelvic circumferential compression devices can be safely applied for all types of pelvic fractures because the effects of the devices on the reduction of fracture fragments are unknown. The aim of this study was to compare the effects of circumferential compression devices on the dynamic realignment and final reduction of the pelvic fractures as a measure of the quality of reduction. METHODS: Three circumferential compression devices were evaluated: the Pelvic Binder, the SAM Sling, and the T-POD. In sixteen cadavers, four fracture types were generated according to the Tile classification system. Infrared retroreflective markers were fixed in the different fracture fragments of each pelvis. The circumferential compression device was applied sequentially in a randomized order with gradually increasing forces applied. Fracture fragment movement was studied with use of a three-dimensional infrared video system. Dynamic realignment and final reduction of the fracture fragments during closure of the circumferential compression devices were determined. A factorial repeated-measures analysis of variance with pairwise post hoc comparisons was performed to analyze the differences in pulling force between the circumferential compression devices. RESULTS: In the partially stable and unstable (Tile type-B and C) pelvic fractures, all circumferential compression devices accomplished closure of the pelvic ring and consequently reduced the pelvic volume. No adverse fracture displacement (>5 mm) was observed in these fracture types. The required pulling force to attain complete reduction at the symphysis pubis varied substantially among the three different circumferential compression devices, with a mean (and standard error of the mean) of 43 ± 7 N for the T-POD, 60 ± 9 N for the Pelvic Binder, and 112 ± 10 N for the SAM Sling. CONCLUSIONS: The Pelvic Binder, SAM Sling, and T-POD provided sufficient reduction in partially stable and unstable (Tile type-B1 and C) pelvic fractures. No undesirable overreduction was noted. The pulling force that was needed to attain complete reduction of the fracture parts varied significantly among the three devices, with the T-POD requiring the lowest pulling force for fracture reduction.

Translocon-associated protein TRAP delta and a novel TRAP-like protein are coordinately expressed with pro-opiomelanocortin in Xenopus intermediate pituitary.

In the intermediate pituitary gland of Xenopus laevis, the expression levels of the prohormone pro-opiomelanocortin (POMC) can be readily manipulated. When the animal is placed on a black background, the gene for POMC is actively transcribed, whereas on a white background the gene is virtually inactive. In this study, we characterized two genes whose transcript levels in the intermediate pituitary are regulated in coordination with that for POMC. One of these codes for a protein homologous to translocon-associated protein TRAP delta, a subunit of a transmembrane protein complex located at the site where nascent secretory proteins enter the endoplasmic reticulum (ER). Both Xenopus and mice were found to express an alternatively spliced transcript that gives rise to a previously unknown version of the TRAP delta protein. The product of the second gene is a novel and highly conserved protein with structural similarity to glycoprotein gp25L, a constituent of another translocon-associated protein complex. A database search revealed the existence of a novel family of gp25L-related proteins whose members occur throughout the animal kingdom. Together, our data imply that (i) the group of ER proteins surrounding translocating polypeptide chains may be far more complex than previously expected, and (ii) a number of the accessory components of the translocon participate in early steps of prohormone biosynthesis.

Molecular probing of the secretory pathway in peptide hormone-producing cells.

The biosynthetic machinery in the melanotrope cells of the Xenopus intermediate pituitary is primarily dedicated to the generation of proopiomelanocortin (POMC)-derived, melanophore-stimulating peptides. Transfer of the animal to a black background stimulates the production of these peptides and causes a dramatic increase in POMC mRNA levels. To identify genes involved in the biosynthesis and regulated release of peptide hormones, we differentially screened an intermediate pituitary cDNA library of toads adapted to a black background with cDNA probes derived from intermediate pituitary mRNA of black- and white-adapted animals. Here we report the identification of twelve distinct genes whose expression levels in the melanotropes are regulated in coordination with that of POMC. Four of these genes are novel while the others code for translocon-associated proteins, a lumenal cysteine protease of the endoplasmic reticulum, prohormone-processing enzymes, members of the granin family and a transmembrane protein presumably involved in the assembly and/or specific functioning of vacuolar H(+)-ATPase from secretory granules. Our results indicate that a wide variety of both soluble and membrane-associated components of the secretory pathway is recruited in physiologically activated, peptide hormone-producing cells.

Isodynamic evaluation of trunk muscles and low-back pain among workers in a steel factory.

A cross-sectional study was conducted to explore the relationship between dynamic parameters of trunk muscle strength and the occurrence of low-back pain (LBP). Isodynamic strength measurements were performed among 31 male maintenance workers with spells of low-back pain in the past 12 months and 28 maintenance workers without a history of low-back pain. In general, workers with low-back pain showed a lower trunk muscle performance than the workers without low-back pain. Only the measures of torque during lateral movement differed significantly between both groups. Regression analysis revealed the importance of the nature of low-back pain for trunk muscle strength. Most parameters of trunk muscle strength were significantly decreased among workers with chronic low-back pain of a rather severe nature, showing reductions from 18% to 50%. None of the work-related risk factors for low-back pain contributed significantly to the prediction of trunk strength measures. The study suggests that isodynamic evaluation of trunk muscle strength may assist in determining objective measures for the severity of low-back pain rather than in evaluating a subject's capability of successfully coping with a specific work load.

Cloning and sequence analysis of pituitary cDNA encoding the beta-subunit of Xenopus proteasome.

The proteasome is a multicatalytic proteinase composed of a number of non-identical subunits. A Xenopus pituitary cDNA was isolated and found to code for the beta-subunit of proteasome. The amino acid sequence deduced from the open reading frame consisted of 215 amino acid residues with a calculated molecular weight of 23,979. A comparative structural analysis indicated that the proteasome subunits can be divided into two groups with the same evolutionary origin. One group consists of subunits with an N-terminally blocked residue and includes components C2, C3, C8 and C9, while the second group of non-blocked proteins includes component C5 and the beta-subunit.