Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings

Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO. Methods: Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20–22 weeks—submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: Emax; pD2) to carbachol or sodium nitroprusside to evaluate endothelial dependent or independent NO-induced vasodilation, or GSNO (exogenous NO vasodilation depending from the endothelial GGT activity). GGT activity was measured using a chromogenic substrate in aortic homogenates. Its role in GSNO-induced relaxation was assessed following inhibition of the enzyme activity (serine-borate complex). That of protein disulfide isomerase (PDI), another redox sensitive enzyme involved in GSNO metabolism, was assessed following inhibition with bacitracin. Results: Aortic GGT activity (18–23 μmol/min/mg of tissue in adult WKY) decreased by 33% in SHR and 45% in SHR with high salt diet. Emax and pD2 for sodium nitroprusside were similar in all groups. Emax for carbachol decreased by −14%, reflecting slight endothelial NO-dependent dysfunction. The GSNO curve was slightly shifted to the left in SHR and in SHR with high salt diet, showing a small enhanced sensitivity to GSNO. Involvements of GGT, as that of PDI, in the GSNO effects were similar in all groups (pD2 for GSNO −0.5 to −1.5 following enzymatic inhibition). Conclusion: Hypertension is associated with a decreased aortic GGT activity without decreasing the vasorelaxant effects of GSNO, whose bioactivity may be supplemented through the alternative enzymatic activity of PDI

Clinical and demographic factors in endometrial and ovary carcinoma: Synchronous carcinoma vs stage IIIA endometrial carcinoma

Objective: To compare pre-surgical demographic and clinical factors and preoperative serum tumor marker values of patients with endometrial and ovarian synchronous carcinoma with those diagnosed with endometrial carcinoma with metastatic ovarian involvement (FIGO stage IIIA). Methods: A retrospective observational study including patients with endometrial and ovarian malignant tumors that were treated at Miguel Servet University Hospital, Zaragoza, Spain, since January 2000 to June 2020. All pathologic specimens were reviewed by two pathologists specialized in gynecological oncology. Results: Overall, 51 patients were included. 24 cases of them, were endometrial and ovarian synchronous primary carcinomas and the remaining 27 cases were endometrial tumors with adnexa. Parity, personal and family oncological history, arterial hypertension, diabetes, dyslipidemia, obesity and the prior use of hormone replacement therapy did not show significant differences between both groups. Age (p = 0.002), menopausal status (p = 0.029), abnormal uterine bleeding (p = 0.001), Ca 12.5 preoperative serum level (p = 0.038) and Ca 19.9 preoperative serum level (0.028) were factors with significant differences between both groups. In multivariate analysis, only abnormal uterine bleeding and Ca 19.9 values were independents factors. Conclusions: The presence of abnormal uterine bleeding and Ca 19.9 preoperative serum level could guide the clinician in the preoperative differential diagnosis between endometrial cancer with ovarian involvement and endometrial and ovarian synchronous carcinoma. © 2021 The Author(s)

MAYA – MAnufacturing of the lining panel using hYbrid technologies; Additive manufacturing, injection moulding and thermoforming

MAYA aims at developing innovative manufacturing routes integrating standard thermoplastic processes (such as injection moulding) and additive manufacturing to produce fuselage composite lining panels. These panels basically consist on sandwich structures with sheets reinforced with fibre-glass hold to the aircraft frame by a set of brackets. The high productivity rate of thermoplastic injection moulding associated to the design freedom of 3D printing will lead to an enhancement of the manufacturing process of the panel-bracket assembly resulting in lighter and less expensive panels with improved overall performance. The work carried out by the research group AMADE focuses on the experimental analysis for interface characterisation, material selection and validation of designs. The first stage of the experimental campaign includes the initial characterisation of the interface bonding of dissimilar materials with different thicknesses obtained by direct 3D printing on the composite skin or by using adhesives under mode I, static and fatigue, and mode II, static, to obtain the best material candidates and design properties. The second part of the work is based on the experimental analysis of the union between the composite skin and small-scale brackets under pull-out and shear-out conditions. Lastly, the final designs of the brackets, both for injection moulding and additive manufacturing, and the corresponding interface bonding with the sandwich panels are validated in large-scale tests under static and fatigue conditions simulating the in-use forces applied to the panels. In this work, the characterisation of the interface bonding of dissimilar materials is presented

Opposite impact of inflammation and oxidative stress on vascular GGT activity

Opposite impact of inflammation and oxidative stress on vascular GGT activity

Endothelial gamma-glutamyltransferase contributes to the vasorelaxant effect of S-nitrosoglutathione in rat aorta

S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide (•NO), plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ−glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and its activity measurement were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), •NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). In each experiment, the role of GGT was assessed using a γ-glutamyl acceptor, glycylglycine, and a non-competitive inhibitor of GGT, serine borate complex. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free •NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In endothelium-intact aorta, half maximal effective concentration (EC50) for GSNO (3.2 ± 0.5.10-7 M) was increased in the presence of serine borate complex serine borate complex (1.6 ± 0.2.10-6 M) and decreased with glycylglycine (4.7 ± 0.9.10-8 M). In endothelium-denuded aorta, EC50 for GSNO alone increased to 2.3 ± 0.3.10-6 M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because new therapeutics treatments based on GSNO are actually developed, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective