Effects of N,N-dimethylformamide and sodium butyrate on enzymes of pyrimidine metabolism in cultured human tumor cells

Effects of a 7-day treatment with the maturational agents DMF and sodium butyrate on enzymes of pyrimidine metabolism, growth rate and cell maturation were assessed in 5 human tumor cell lines, ARH-77 (myeloma), K-562 (chronic myeloid leukemia), KG-1 (myeloid leukemia), HL-60 (promyelocytic leukemia) and RWLy-1 (non-Hodgkin's lymphoma). DMF lengthened the doubling times of all five cell lines while sodium butyrate lengthened only those of K-562, HL-60 and RWLy-1. Full maturation was induced only in HL-60 by either agent and in K-562 by butyrate. Exposure resulted in a decreased activity of the anabolic enzyme orotate phosphoribosyltransferase (EC 2.4.2.10) and increased activities of the catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrouracil dehydrogenase (EC 1.3.1.2). Changes in the amphibolic enzyme, uridine phosphorylase (EC 2.4.2.3) did not follow any apparent pattern. This study indicates that the pattern of pyrimidine metabolism differs between the differentiated and slowly growing, and undifferentiated rapidly growing counterpart of several human tumors, suggesting that enzymes of pyrimidine metabolism can be used as markers for cellular growth and/or maturity.     

Insulin Derived Fibrils Induce Cytotoxicity in vitro and Trigger Inflammation in Murine Models

Background:Effective exogenous insulin delivery is the cornerstone of insulin dependent diabetes mellitus management. Recent literature indicates that commercial insulin-induced tissue reaction and cellular cytotoxicity may contribute to variability in blood glucose as well as permanent loss of injection or infusion site architecture and function. It is well accepted that insulin formulations are susceptible to mechanical and chemical stresses that lead to insulin fibril formation. This study aims to characterize in vitro and in vivo toxicity, as well as pro-inflammatory activity of insulin fibrils.Method:In vitro cell culture evaluated cytotoxicity and fibril uptake by macrophages and our modified murine air-pouch model quantified inflammatory activity. The latter employed FLOW cytometry and histopathology to characterize fibril-induced inflammation in vivo, which included fibril uptake by inflammatory phagocytes.Results:These studies demonstrated that insulin derived fibrils are cytotoxic to cells in vitro. Furthermore, inflammation is induced in the murine air-pouch model in vivo and in response, macrophages uptake fibrils both in vitro and in vivo.Conclusions:Administration of insulin fibrils can lead to cytotoxicity in macrophages. In vivo data demonstrate insulin fibrils to be pro-inflammatory which over time can lead to cumulative cell/tissue toxicity, inflammation, and destructive wound healing. Long term, these tissue reactions could contribute to loss of insulin injection site architecture and function.     

Über Brucheinklemmung und Kriegsernährung

Ohne Zusammenfassung     

Are cognitive researchers ignoring their senses? The problem of sensory deficit in cognitive aging research

Sensory impairments are common in older adult populations and have notable impacts on aging outcomes. Relationships between sensory and cognitive functions have been clearly established, though the mechanisms underlying those relationships are not fully understood. Given the growing burden of dementia, older adults with sensory deficits are an important and growing population to study in cognitive aging research. Yet, cognitive research sometimes excludes those with uncorrected significant/severe sensory deficits and often poorly or inconsistently assesses those deficits. Observational and interventional studies that exclude participants with sensory deficits will be limited in their generalizability to the narrower subset of the older adult population without vision or hearing impairment and may be missing an opportunity to study a growing population of older adults at higher risk of cognitive impairment. Strategies exist for adapting cognitive testing instruments, and inroads could be made into collecting normative data to inform ongoing research. Bringing together psychometricians with researchers who specialize in vision and hearing impairments could launch highly innovative research on both measurement methods and cognitive disease etiology, as sensory organs provide readily accessible neuronal and vascular beds that may show pathology earlier and elucidate innovative screening opportunities for early signs of cognitive disease.