ABSTRACT
BACKGROUND: Most Alzheimer's disease (AD) cases arise sporadically and may involve innate immune activation of microglial expressed Toll-like receptors regulated through the myeloid differentiation protein 88 (MyD88) pathway. OBJECTIVE: It was the aim of this study to test the innate immune involvement in AD pathology. METHODS: We mated APPsw/PS1ΔE9 mice with MyD88-deficient mice. RESULTS: Progeny mice had similar levels of soluble amyloid-ß peptides, amyloid plaque density and neuroimmune staining patterns. However, double-transgenic mice did show a significantly reduced life expectancy. CONCLUSION: Our findings indicate that impaired innate immune responses may play a role in AD pathology.
Subject(s)
Alzheimer Disease/immunology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Brain/pathology , Myeloid Differentiation Factor 88/deficiency , Amyloid beta-Peptides/metabolism , Animals , Brain/immunology , Brain/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Mice , Mice, Transgenic , Plaque, Amyloid/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVES: This study was carried out to determine the prognosis, and the clinical approach, in fetuses with umbilical cord cysts, during the second and third trimesters of gestation, according to our experience and data in the current literature. METHODS: We identified 10 fetuses with umbilical cord cysts that were diagnosed during the second and third trimesters of pregnancy at three referral centers. All underwent detailed ultrasound evaluation at the time of diagnosis and during follow-up. Prenatal karyotype testing was offered to all women. A MEDLINE review of the literature published from 1980 to 2009 was carried out to identify previous studies and case reports of fetuses with umbilical cord cysts. RESULTS: In our series of 10 cases, significant additional abnormalities were observed in two during a detailed sonogram. In one case, trisomy 18 was diagnosed, leading to pregnancy termination, and in the other case a neonate with heart defects and a normal karyotype was born. These results differ from those reported in the literature, in which the association between second- and third-trimester umbilical cord cysts and fetal anomalies ranged from 38 to 100%. CONCLUSIONS: In our study, as in other publications, an association was found between the presence of second- and third-trimester umbilical cord cysts and fetal anomalies. The strong association between second- and third-trimester umbilical cord cysts and aneuploidy in the literature seems to be biased, mainly because of the tendency to report abnormal cases. When these findings are accompanied by additional sonographic abnormalities, the association with aneuploidy is clear and should be an indication for fetal karyotype testing.
Subject(s)
Trisomy/diagnosis , Urachal Cyst/diagnostic imaging , Adult , Female , Humans , Karyotyping , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Prognosis , Trisomy/pathology , Ultrasonography, Prenatal , Urachal Cyst/complications , Urachal Cyst/embryology , Young AdultABSTRACT
Heart cells in culture were used to clarify whether furosemide or digoxin cause thiamine deficiency and if so, by what mechanism. The intracellular level of thiamine pyrophosphate gradually decreased, with a half-life of 16-19 days, after treatment of cardiac cells with furosemide or digoxin. When thiamine was excluded from the growth medium, thiamine pyrophosphate levels gradually decreased, with a half-life of 5-6 days. No additive effect was observed in the presence of the above drugs when thiamine was excluded from the medium. Thiamine uptake by cardiac cells grown in a thiamine-free medium for 7 days decreased significantly in the presence of furosemide or digoxin. The effect of furosemide or digoxin on thiamine uptake was found to be dose dependent. Co-administration of furosemide and digoxin to the cardiac cell cultures resulted in an additive effect on thiamine uptake. Our results demonstrate that furosemide and digoxin inhibit thiamine uptake by cardiac cells in culture and may therefore cause thiamine deficiency in patients undergoing chronic treatment with these drugs.
