64 research outputs found

    Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies

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    Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations.Peer reviewe

    Variability in transport of terrigenous material on the shelves and the deep Arctic Ocean during the Holocene

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    Arctic coastal zones serve as a sensitive filter for terrigenous matter input onto the shelves via river discharge and coastal erosion. This material is further distributed across the Arctic by ocean currents and sea ice. The coastal regions are particularly vulnerable to changes related to recent climate change. We compiled a pan-Arctic review that looks into the changing Holocene sources, transport processes and sinks of terrigenous sediment in the Arctic Ocean. Existing palaeoceanographic studies demonstrate how climate warming and the disappearance of ice sheets during the early Holocene initiated eustatic sea-level rise that greatly modified the physiography of the Arctic Ocean. Sedimentation rates over the shelves and slopes were much greater during periods of rapid sea-level rise in the early and middle Holocene, as a result of the relative distance to the terrestrial sediment sources. However, estimates of suspended sediment delivery through major Arctic rivers do not indicate enhanced delivery during this time, which suggests enhanced rates of coastal erosion. The increased supply of terrigenous material to the outer shelves and deep Arctic Ocean in the early and middle Holocene might serve as analogous to forecast changes in the future Arctic.Peer reviewe

    Variability in transport of terrigenous material on the shelves and the deep Arctic Ocean during the Holocene

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    Arctic coastal zones serve as a sensitive filter for terrigenous matter input onto the shelves via river discharge and coastal erosion. This material is further distributed across the Arctic by ocean currents and sea ice. The coastal regions are particularly vulnerable to changes related to recent climate change. We compiled a pan-Arctic review that looks into the changing Holocene sources, transport processes and sinks of terrigenous sediment in the Arctic Ocean. Existing palaeoceanographic studies demonstrate how climate warming and the disappearance of ice sheets during the early Holocene initiated eustatic sea-level rise that greatly modified the physiography of the Arctic Ocean. Sedimentation rates over the shelves and slopes were much greater during periods of rapid sea-level rise in the early and middle Holocene, as a result of the relative distance to the terrestrial sediment sources. However, estimates of suspended sediment delivery through major Arctic rivers do not indicate enhanced delivery during this time, which suggests enhanced rates of coastal erosion. The increased supply of terrigenous material to the outer shelves and deep Arctic Ocean in the early and middle Holocene might serve as analogous to forecast changes in the future Arctic.Peer reviewe

    2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

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    HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action

    Book review of Pascale, C.-M. (2021). Living on the Edge. When Hard Times Become a Way of Life.

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