Refine
Document Type
- Article (4)
Language
- English (4)
Has Fulltext
- yes (4)
Is part of the Bibliography
- no (4)
Keywords
Institute
- Universitätsmedizin (4) (remove)
Publisher
- S. Karger AG (3)
- MDPI (1)
Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test
(2019)
Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations
within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous,
multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to
demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study
was to establish a test that allows for an objective assessment of the pathological potential of NPC1
gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in
lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying
distinct sequence variants. Filipin staining was used to test for complementation of the phenotype.
The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and
24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys
showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met,
and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr
acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the
variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance.
Moreover, we present a system that can be utilized to screen for new drugs.
Histopathologic and Clinical Subtypes of Autoimmune Pancreatitis: The Honolulu Consensus Document
(2011)
Autoimmune pancreatitis (AIP) has been extensively reported from Japan, Europe and the USA. While the descriptions of AIP from Japan have predominantly been based on the presence of a distinct clinical phenotype, reports from Europe and the USA describe at least 2 histopathologic patterns in patients diagnosed with AIP, namely lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) or granulocytic epithelial lesion- positive pancreatitis. While the 2 entities share common histopathologic features (periductal lymphoplasmacytic infiltration and peculiar periductal fibrosis), expert pathologists can accurately distinguish them on the basis of other unique histopathologic features. Clinically, the 2 entities have a similar presentation (obstructive jaundice/pancreatic mass and a dramatic response to steroids), but they differ significantly in their demography, serology, involvement of other organs and disease relapse rate. While LPSP is associated with elevation of titers of nonspecific autoantibodies and serum IgG4 levels, IDCP does not have definitive serologic autoimmune markers. All experts agreed that the clinical phenotypes associated with LPSP and IDCP should be nosologically distinguished; however, their terminology was controversial. While most experts agreed that the entities should be referred to as type 1 and type 2 AIP, respectively, others had concerns regarding use of the term ‘autoimmune’ to describe IDCP.
Background: Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. Summary: A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.
Background: Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. Summary: A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.