γ-Glutamyltranspeptidase-Triggered Intracellular Gadolinium Nanoparticle Formation Enhances the T2-Weighted MR Contrast of Tumor.

Magnetic resonance imaging (MRI) is advantageous in the diagnosis of deep internal cancers, but contrast agents (CAs) are always needed to improve MRI sensitivity. Gadolinium (Gd)-based agents are routinely used as T1-dominated CAs in clinic but using intracellularly formed Gd nanoparticles to enhance the T2-weighted MRI of tumor in vivo at high magnetic field has not been reported. Herein, we rationally designed a "smart" Gd-based probe Glu-Cys(StBu)-Lys(DOTA-Gd)-CBT (1), which was subjected to γ-glutamyltranspeptidase (GGT) cleavage and an intracellular CBT-Cys condensation reaction to form Gd nanoparticles (i.e., 1-NPs) to enhance the T2-weighted MR contrast of tumor in vivo at 9.4 T. Living cell experiments indicated that the 1-treated HeLa cells had an r2 value of 27.8 mM-1 s-1 and an r2/r1 ratio of 10.6. MR imaging of HeLa tumor-bearing mice indicated that the T2 MR contrast of the tumor enhanced 28.6% at 2.5 h post intravenous injection of 1. We anticipate that our probe 1 could be employed for T2-weighted MRI diagnosis of GGT-related cancers in the future when high magnetic field is available in clinic.

Pre-administration of rats with Helicobacter pylori γ-glutamyl-transpeptidase alleviates osteoarthritis.

OBJECTIVE: To determine the efficacy of Helicobacter pylori γ-glutamyl-transpeptidase (GGT) in osteoarthritis (OA) therapy. RESULTS: Oral administration of rats with rGGT alleviated joint pain in the acute phase of iodoacetate (IA)-induced OA. The CXCL1/IL-6 in blood and in articular tissue as well as circulating granulocytes in the recipients of GGT, were reduced. This might be associated with the expansion of regulatory T cells in the inguinal lymph nodes and increased articular IL-10. CONCLUSION: We provide preclinical evidence that H. pylori GGT may represent a promising candidate for OA therapy.

Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice.

The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.

Serum γ - glutamyltransferase activity as an indicator of chronic liver injury in cattle with no clinical signs / γ - glutamiltransferase como indicador de lesão hepática crônica em bovinos sem sinais clínicos

This study aimed to determine the power of the serum aspartate aminotransferase (AST) and gamma-glutamyltransferasase (GGT) activities and of the albumin and cholesterol dosages for detecting hepatic histopathological injuries. A total of 220 healthy male Nelore cattle that had been extensively bred were evaluated. Blood and liver samples were collected on the day of slaughter for biochemical and histopathological tests. The results showed that the sensitivity to AST, GGT, albumin, and cholesterol tests were respectively 22.4%, 22.4%, 36%, and 37.2%.

Determinou-se a capacidade da dosagem das atividades séricas da aspartato aminotransferase (AST) e gama-glutamiltransferase (GGT) e das dosagens de albumina e de colesterol para a detecção de lesões histopatológicas hepáticas. Foram avaliados 220 bovinos, machos da raça Nelore, criados de forma extensiva. Amostras de sangue e de fígado foram coletadas para a realização dos testes histopatológicos e bioquímicos no dia do abate. Os resultados mostraram que a sensibilidade dos testes de AST, GGT, albumina e colesterol foram, respectivamente, de 22,4%, 22,4%, 36%, e 37,2%. A especificidade dos testes AST, GGT, albumina e colesterol foram, respectivamente, de 78,8%, 90,4%, 75,6% e 68,3%.

Effect of enhancing curd formation during the first colostrum feed on absorption of gamma glutamyl transferase by newborn calves.

OBJECTIVE: To examine the effects of curd formation within the abomasum, on the absorption of gamma glutamyl transferase (GGT) from colostrum in newborn calves. DESIGN: An in vivo physiological study with controls, and in vitro examination of calf abomasal fluid. PROCEDURES: Newborn calves were taken from cows without allowing them to suckle. They were fed either 1.5 kg colostrum or 1.5 kg colostrum plus rennet, with intervals between calving and colostrum feeding ranging from 0.4 to 12.7 h. Absorption of proteins from the whey component of colostrum was assessed from the rise in activity of serum GGT. In in vitro studies, colostrum was incubated with bovine amniotic fluid, newborn calf abomasal fluid or newborn calf forestomach contents, with or without rennet, to test the curd inhibiting effects of components in the abomasal fluid of newborn calves. RESULTS: In vivo: addition of rennet to the colostrum feed reduced the proportion of calves with serum GGT activity below 500 U/L by 60%. In vitro: 43% of newborn calves lacked curd forming activity in their abomasal fluid, and that deficiency was corrected by adding rennet to the incubation medium. CONCLUSIONS: Some calves are born with low amounts of curd forming enzyme activity in the abomasum. This may compromise their ability to absorb large whey proteins from the first feed of colostrum. Adding rennet to the first colostrum feed may improve passive immunity in those calves.

Clearance of purified human liver gamma-glutamyltransferase after intravenous injection in the rat.

The clearance of gamma-glutamyltransferase was studied by injecting the purified human liver enzyme intravenously in the rat. The results show a biphasic clearance, with a rapid initial rate of removal. The initial uptake is more rapid for neuraminidase-treated GT. Liver accounts for the bulk organ uptake and the enzyme is almost exclusively taken up into the parenchymal cells. We suggest that the uptake of circulating GT is receptor mediated, most likely by the galactose receptor of the parenchymal cells.

Utilizaçäo da dosagem da gama glutamil transferase associada ao teste cage no diagnóstico do alcoolismo na empresa / Used of gamma glutamyltransferase dosage associated is CAGE test in diagnosis of alcoholism in refinery

No curso do exame periódico anual, realizxado em 1986, numa Refinaria de Petróelo, foram solicitadas dosagens de yGT em todos os empregados, independente do uso ou näo de bebidas alcoólicas. Para os bebedores, sem considerar o grau de ingestäo, foi aplicado o questionário CAGE. As dosagens da yGT solicirtadas juntamente e outros exames complementares foram feitas por um único laboratório. O teste CAGE foi aplicado durante a anamnese por médicos do trabalho pertencentes à empresa e previamente orientados para que houvesse uniformidade. Os 944 indivíduos pesquisados foram dividiso em dois grandes grupos: o de bebdores e o de näo bebedores. O grupo de näo bebedores foi separado com relaçäo a yGT normal e elevada. No grupo de bebedores, separados como o anterior, foi feita correlaçäo com o teste CAGE. Os resultados foram comparados com os existentes na literatura e demonstraram a utilidade da associaçäo desses dois indicadores