A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

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Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Hepatoprotective effects of diethylcarbamazine in acute liver damage induced by carbon tetrachloride in rats

This research was carried out to determine a potential role of leukotrienes in the acute hepatotoxicity induced by CC14 in rats. An inhibitor of leukotrienes biosynthesis, diethylcarbamazine (DEC, 25 and 50 mg ·kg-1 ip) exerted hepatoprotective effects, decreasing the activity of alanine aminotransfer-ase in serum and the concentration of liver triglycerides. DEC reduced histological damage of liver evidenced by electron microscopy. The hepatoprotective effects of DEC were dose-dependent. The results favor the role of leukotrienes in CC14 hepatotoxicity.     

Use of a synthetic peptide-based elisa for the diagnosis of infectious mononucleosis and other diseases

A simple enzyme immunoassay has been developed based on measuring antibodies to synthetic peptides corresponding to sequences in the Epstein-Barr nuclear antigen (EBNA). This assay, which is reproducible, quantitative, and simple to perform and interpret, can be an effective tool to aid in the diagnosis of infectious mononucleosis and nasopharyngeal carcinoma.     

Primary Amine‐Initiated Polymerizations of Alanine‐NCA and Sarcosine‐NCA

Summary: Sarcosine‐N‐carboxyanhydride (Sar‐NCA), L ‐alanine‐NCA and D,L ‐alanine‐NCA were polymerized with benzylamine as initiator in three different solvents: dichloromethane (CH₂Cl₂), 1,4‐dioxane and dimethylformamide (DMF). The isolated polyaminoacids were characterized by ¹H NMR spectroscopy and MALDI‐TOF mass spectrometry. High conversions and degrees of polymerization s close to the monomer‐initiator (M/I) ratios were found for all polypeptides. For polysarcosine which was soluble under the given reaction conditions a narrow monomodal frequency distribution was found. In contrast, a broad frequency distribution was observed, when L ‐alanine NCA was polymerized in dioxane and DMF. These results were attributed to a partial precipitation of oligopeptides in the β‐sheet structure, which reduces the reactivity of endgroups for steric reasons. The polymerizations of D,L ‐alanine‐NCA showed features in between the extremes of Sar‐NCA and L ‐Ala‐NCA.

Schematic illustration of the secondary structures formed in a primary amine initiated polymerization of L ‐Ala‐NCA.     

Alterations in alanine metabolism in diabetic dogs during short-term treatment with an artificial B cell

Summary The flux rates of plasma glucose and alanine were studied isotopically (6-³H-glucose and U-¹⁴C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.     

Pyruvate kinase in human brain tumours. Its significance in the treatment of gliomas

Summary Pyruvate kinase isozyme distribution was studied in 101 intracranial tumours of various nature and origin, and in normal human brain (both foetal and adult). In foetal brain, five different forms could be detected by electrophoresis (K₄, K₃M, K₂M₂, KM₃, and M₄). In adult brain, the M₄ type, K₃M hybrid, and K₄ are present; the M type is largely predominant. Alanine inhibition of pyruvate kinase can be used to discriminate between M and K-type pyruvate kinase. The results obtained in an alanine inhibition test are in agreement with the electrophoretic pattern. Pyruvate kinase from foetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. In adult brain a high residual activity of pyruvate kinase is found in the presence of alanine. Well differentiated neuroepithelial tumours,i.e., astrocytomas, oligodendrogliomas, and ependymomas showed also relatively high residual activities, though less than in normal adult brain. On the contrary, in poorly differentiated gliomas low residual activity was found. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumours. There is also a strong correlationship between alanine inhibition of pyruvate kinase and one year survival after total or subtotal resection of gliomas in adults.When in gliomas the residual activity is determined not in the centre of the tumour but more towards the periphery, much higher residual activity is found. It is suggested that brain biopsies in which a residual activity higher than 70% is found probably contain no tumour in the paraffin slides.Poorly differentiated gliomas were characterized by the presence of type K, and the hybrids K₃M. In well differentiated gliomas, besides K₄ and K₃M, M₄ was also present. Alanine inhibition was in agreement with the electrophoretic pattern in all tumours. In children (age 1–11 years) gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading. Of the non-neuro-epithelial tumours studied relatively high residual activities were found for pyruvate kinase in haemangioblastomas, chromophobe adenomas, and craniopharyngiomas. This was also found in an arteriovenous malformation. Other non-neuroepithelial tumours showed much less residual activity. These included benign tumours, meningiomas, neurilemmomas, malignant metastatic tumours, and fibrosarcomas. It was also found in cavernomas. The determination of pyruvate kinase activity in the presence of alanine may be useful for the diagnosis and treatment of intracerebral tumours, in particular gliomas of adults.The alanine inhibition test is a reliable quantitative procedure. It can be performed in 10 minutes, and may well fit in the scope of a surgical procedure.