Protective action of glutamine in rats with severe acute liver failure

BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function.Thioacetamide(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress.AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced IHAG.METHODS Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory process.RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P 0.001), GSH(P 0.01), IL-1β, IL6, and TNFα levels(P 0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P 0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P0.01, P 0.01, and P 0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P 0.05), NQO1, and SOD(P 0.01), as well as levels of IL-10(P 0.001), while decreasing expression of Keap1, TLR4, NFκB(P 0.001), COX-2 and iNOS,(P 0.01), and reducing NO_2 and NO_3 levels(P 0.05).CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway,thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.     

Long-term results and tolerability of tandem peptide receptor radionuclide therapy with <Superscript>90</Superscript>Y/<Superscript>177</Superscript>Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study

Introduction

The peptide receptor radionuclide therapy (PRRT) with ⁹⁰Y and ¹⁷⁷Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET).

Aim

The aim of the study was to evaluate clinical results and long-term side effects of tandem ⁹⁰Y /¹⁷⁷Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site.

Materials and methods

59 patients with disseminated NET were included in the study prospectively. 3–5 cycles of combined 1:1 ⁹⁰Y/¹⁷⁷Lu-DOTATATE (total injected activity 11.1–16.65 GBq) with mixed amino acids for kidney protection were performed.

Results

During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor’s site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed.

Conclusions

These results indicated the tandem ⁹⁰Y/¹⁷⁷Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.

     

New Coordination Polymers of Selected Lanthanides with 1,2-Phenylenediacetate Linker: Structures,Thermal and Luminescence Properties

Solvothermal reactions of lanthanide (III) salts with 1,2-phenylenediacetic acid in N,N′-dimethylformamide (DMF) solvent lead to the formation of the metal complexes of the general formula Ln₂(1,2-pda)₃(DMF)₂, where Ln(III) = Pr(1), Sm(2), Eu(3), Tb(4), Dy(5), and Er(6), 1,2-pda = [C₆H₄(CH₂COO)₂]²⁻. The compounds were characterized by elemental analysis, powder and single-crystal X-ray diffraction methods, thermal analysis methods (TG-DSC and TG-FTIR), infrared and luminescence spectroscopy. They exhibit structural similarity in the two groups (Pr, Sm, and Eu; Tb, Dy, and Er), which was reflected in their thermal behaviours and spectroscopic properties. Single-crystal X-ray diffraction studies reveal that Sm(2) and Eu(3) complexes form 2D coordination polymers with four crystallographically independent metal centers. Every second lanthanide ion is additionally coordinated by two DMF molecules. The 1,2-phenylenediacetate linker shows different denticity being: penta- and hexadentate while carboxylate groups exhibit bidentate-bridging, bidentate-chelating, and three-dentate bridging-chelating modes. The infrared spectra reflect divergence between these two groups of complexes. The complexes of lighter lanthanides contain in the structure coordinated DMF molecules, while in the structures of heavier complexes, DMF molecules appear in the inner and outer coordination sphere. Both carboxylate groups are deprotonated and engaged in the coordination of metal centers but in different ways in such groups of complexes. In the groups, the thermal decomposition of the isostructural complexes occurs similarly. Pyrolysis of complexes takes place with the formation of such gaseous products as DMF, carbon oxides, ortho-xylene, ethers, water, carboxylic acids, and esters. The complexes of Eu and Tb exhibit characteristic luminescence in the VIS region, while the erbium complex emits NIR wavelength.     

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of kidney lesions: A review

Traditionally, treatment of renal lesions is indicated based only on imaging features. Although controversy exists about tissue sampling from small renal masses, renal biopsy is indicated in some cases. In this review, we discuss the rationale for endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) andsummarize the recent advances in this field, providing recommendations for the practicing clinician. The use of EUS-FNA appears to be a safe and feasible means of confirming or excluding malignancy. EUS allows assessment and biopsy of masses or lesions within both kidneys and related complications are rare. The main advantages of EUS-FNA are that it can be done as an outpatient procedure, with good results, minimal morbidity and a short hospital stay. Nevertheless, EUS-FNA of renal masses should be indicated only in selected cases, in which there is potential to decrease unnecessary treatment of small renal masses and to best select tumors for active surveillance and minimally invasive ablative therapies. Additionally, some renal lesions may be ineligible for EUS-guided biopsy because of anatomical limitations. EUS-FNA renal biopsy will probably be best applied to central anterior renal masses, while tumors on the posterior aspect of the kidney, percutaneous access will probably be superior.