ABSTRACT
Abstract Background: To date there are no specific classification criteria for childhood-onset systemic lupus erythematosus (cSLE). This study aims to compare the performance among the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics criteria (SLICC) and the new European League Against Rheumatism (EULAR)/ACR criteria, in a cSLE cohort. Methods: We conducted a medical chart review study of cSLE cases and controls with defined rheumatic diseases, both ANA positive, to establish each ACR1997, SLICC and EULAR/ACR criterion fulfilled, at first visit and 1-year-follow-up. Results: Study population included 122 cSLE cases and 89 controls. At first visit, SLICC criteria had higher sensitivity than ACR 1997 (89.3% versus 70.5%, p < 0.001), but similar specificity (80.9% versus 83.2%, p = 0.791), however performance was not statistically different at 1-year-follow-up. SLICC better scored in specificity compared to EULAR/ACR score ≥ 10 at first visit (80.9% versus 67.4%, p = 0.008) and at 1-year (76.4% versus 58.4%, p = 0.001), although sensitivities were similar. EULAR/ACR criteria score ≥ 10 exhibited higher sensitivity than ACR 1997 (87.7% versus 70.5%, p < 0.001) at first visit, but comparable at 1-year, whereas specificity was lower at first visit (67.4% versus 83.2%, p = 0.004) and 1-year (58.4% versus 76.4%, p = 0.002). A EULAR/ACR score ≥ 13 against a score ≥ 10, resulted in higher specificity, positive predictive value, and cut-off point accuracy. Compared to SLICC, a EULAR/ACR score ≥ 13 resulted in lower sensitivity at first visit (76.2% versus 89.3%, p < 0.001) and 1-year (91% versus 97.5%, p = 0.008), but similar specificities at both assessments. When compared to ACR 1997, a EULAR/ACR total score ≥ 13, resulted in no differences in sensitivity and specificity at both observation periods. Conclusions: In this cSLE population, SLICC criteria better scored at first visit and 1-year-follow-up. The adoption of a EULAR/ACR total score ≥ 13 in this study, against the initially proposed ≥10 score, was most appropriate to classify cSLE. Further studies are necessary to address if SLICC criteria might allow fulfillment of cSLE classification earlier in disease course and may be more inclusive of cSLE subjects for clinical studies.
Subject(s)
Animals , Humans , Brain/metabolism , Pharmaceutical Preparations/metabolism , Blood-Brain Barrier/metabolism , Tissue Distribution/physiology , Models, Theoretical , Arachnoid/drug effects , Arachnoid/metabolism , Biological Transport/drug effects , Biological Transport/physiology , Brain/drug effects , Pharmaceutical Preparations/administration & dosage , Blood-Brain Barrier/drug effects , Tissue Distribution/drug effects , Extracellular Fluid/drug effects , Extracellular Fluid/metabolismABSTRACT
Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding), the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD) and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.
Subject(s)
Humans , Alzheimer Disease/metabolism , /physiology , Alzheimer Disease/physiopathology , Biological Transport/physiology , Cholesterol/physiology , Gallstones/metabolism , Gallstones/physiopathology , Gene Expression Regulation/physiology , Homeostasis/physiology , Kidney Diseases/metabolism , Kidney Diseases/physiopathology , /genetics , /metabolism , Tissue Distribution/physiologyABSTRACT
The placenta is an essential organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. It is known that the placenta growth factor (PlGF)is a member of the vascular endothelial growth factor family and is critical for placental growth and fetal development. However, there is little information regarding the expression pattern and cellular localization of PlGF mRNA in rat placenta during pregnancy. The aim of this study was to define the distribution of PlGF mRNA in rat placenta at various gestations. RT-PCR analysis showed that the expression level of PlGF mRNA increased as gestation advanced. Using in situ hybridization histochemistry, positive cells of PlGF mRNA were detected in chorionic villi. PlGF mRNA was expressed in the trophoblast cells and stroma cells surrounding the blood vessels within chorionic villi on day 13 and 15. Also, positive signals of PlGF mRNA were strongly detected in stroma cells of chorionic villi on day 17, 19, and 21. In particular, the density and number of positive signals of PlGF mRNA was significantly increased as gestation advanced. The expression pattern of PlGF mRNA in rat placenta during pregnancy demonstrates that PlGF plays a functional role for placental growth and fetal development during mid-late pregnancy.
Subject(s)
Animals , Female , Pregnancy , Rats , Gene Expression Regulation/physiology , Placenta/metabolism , Pregnancy Proteins/metabolism , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Tissue Distribution/physiologyABSTRACT
A neuromedina B (NB) e o peptídeo liberador de gastrina são peptídeos bombesina-símiles encontrados em mamíferos, inclusive em seres humanos. Ambos inibem a secreção hipofisária de tireotrofina (TSH); entretanto, somente a NB tem importância fisiológica demonstrada. A NB é produzida em abundância em tireotrofos e parece inibir a secreção de TSH por via autócrina, uma vez que o bloqueio do peptídeo endógeno causa aumento na liberação do TSH, tanto in vivo quanto in vitro. A NB é positivamente regulada pelos hormônios tireóideos (HT). Os HT aumentam o conteúdo de neuromedina B e do seu RNAm em adeno-hipófises de ratos hipotireóideos, poucas horas após sua administração, o que coincide com diminuição do TSH sérico. Isto nos levou a sugerir que a NB possa ser um intermediário protéico envolvido na inibição aguda da liberação de TSH induzida pelos HT. O TRH também altera rapidamente a expressão da NB. Quinze e 30 minutos após a administração do TRH em ratos normais já há diminuição do conteúdo hipofisário de NB e dos níveis do seu RNAm. No jejum e diabetes experimental, que se caracterizam por diminuição de HT séricos com níveis inadequadamente normais ou diminuídos de TSH, ocorre aumento do conteúdo de NB e de seu RNAm. O análogo de somatostatina, octreotide, também é capaz de aumentar o conteúdo de NB. Assim, a neuromedina B é um importante inibidor local da secreção de TSH, podendo ser uma via final comum de hormônios e neuro-hormônios que determinam variações na secreção de TSH.
Subject(s)
Humans , Animals , Bombesin/physiology , Gastrin-Releasing Peptide/physiology , Hypothalamo-Hypophyseal System/metabolism , Bombesin/analogs & derivatives , Tissue Distribution/physiology , Mammals , Receptors, Bombesin/physiology , Thyrotropin/antagonists & inhibitors , Thyrotropin/metabolismABSTRACT
The biodistribution and removal from plasma (measured as fractional clerance rate, FCR, per hour) of native and oxidatively modified (99m)technetium-labeled Beta-very low density lipoprotein ((99m)Tc-Beta-VLDL)) were investigated in hypercholesterolemic (HC) and control (C) three-month old New Zealand rabbits. The intracellular accumulation of Beta-VLDL labeled with (99m)Tc was studied in vitro in THP-1 cells and monocyte-derived macrophages isolated from rabbits. After intravenous injection into C rabbits, copper-oxidized Beta-VLDL ((99m)Tc-ox-Beta-VLDL)) was cleared from the circulation faster (0.362 + 0.070/h) than native Beta-VLDL ((99m)Tc-nat-Beta-VLDL, 0.241 + 0.070/h)). In contrast, the FCR of (99m)Tc-ox-Beta-VLDL in HC rabbits was lower (0.100 + 0.048/h) than that of (99m)Tc-nat-Beta-VLDL (0.163 + 0.043/h). The hepatic uptake of radiolabeled lipoproteins was lower in HC rabbits (0.114 + 0.071 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.116 + 0.057 percent injected dose/g tissue for (99m) Tc-ox-Beta-VLDL) than in C rabbits (0.301 + 0.113 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.305 + 0.149 percent injected dose/g tissue for ((99m)Tc-ox-Beta-VLDL). The uptake of (99m)Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL by atherosclerotic aorta lesions isolated from HC rabbits ((99m)Tc-nat-Beta-VLDL:0.033 + 0.012 percent injected dose/g tissue and (99m)Tc-ox-Beta-VLDL: 0.039 + 0.017 percent injected dose/g tissue) was higher in comparison to that of non-atherosclerotic aortas from C rabbits (99m)Tc-nat-Beta-VLDL: 0.023 + 0.010 percent injected dose/g tissue and (99m)Tc-ox-Beta VLDL: 0.019 + 0.010 percent injected dose/g tissue). However, (99m) Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL were taken up by atherosclerotic lesions at similar rates. In vitro studies showed that both monocyte-derived macrophages isolated from rabbits and THP-1 macrophages significantly internalized more (99m)Tc-ox-Beta-VLDL than (99m)Tc-nat-Beta-VLDL. These results indicate that in cholesterol-fed rabbits (99m)Tc-ox-Beta-VLDL is slowly cleared from plasma and accumulates in atherosclerotic lesions. However, although the extent of in vitro uptake of (99m)Tc-ox-Beta-VLDL by macrophages was high, the in vivo accumulation of this radiolabeled lipoprotein by atherosclerotic lesions did not differ from that of (99m)Tc-nat-Beta-VLDL.
Subject(s)
Rabbits , Animals , Male , Atherosclerosis/metabolism , Lipids/blood , Lipoproteins, VLDL/blood , Lipoproteins, VLDL/isolation & purification , Lipoproteins, VLDL/pharmacology , Macrophage Activation/physiology , Sodium Pertechnetate Tc 99m/blood , Sodium Pertechnetate Tc 99m/isolation & purification , Sodium Pertechnetate Tc 99m/pharmacokinetics , Tissue Distribution/physiology , Autoradiography , Metabolic Clearance RateABSTRACT
Distribution study using 75Se shows that maximum accumulation was in liver tissues after 24h of 75Se administration. Induction of selenium binding protein (Se-P) in hepatic tissues of chick embryo was observed. Chick embryo hepatic Se-P was isolated after 24h of 75Se treatment using Sephadex G-75 column chromatography. Fractions of induced protein shows the presence of maximum concentration of 75Se. This induced protein was found to have an approximate molecular weight of 56 KD on molecular sieve. It also showed an absorbance maxima at 254 nm, which indicates the presence of high concentrations of sulphydryl groups.
Subject(s)
Animals , Carrier Proteins/isolation & purification , Chick Embryo , Liver/chemistry , Selenium , Selenium Radioisotopes/diagnosis , Selenium-Binding Proteins , Tissue Distribution/physiologyABSTRACT
El anticuerpo monoclonal (AcMo) B2C114, dirigido contra el antígeno carcinoembrionario (CEA) fue conjugado con el anhídrido bicíclico del DTPA (CA-DTPA) usando diferentes relaciones molares CA-DTPA: AcMo desde 1:1 hasta 30:1. Se determinó para cada caso la eficiencia de acoplamiento y el número de moléculas de DTPA por molécula de AcMo. Se realizó la marcación con 111In para todas las relaciones molares CA-DTPA: AcMo y se determinó la pureza radioquímica por cromatografía instantánea en placa delgada (ITLC Gelman SG) y cromatografía en gel (Sephadex G-25). La biodistribución del AcMo marcado en ratones normales Balb/c y en portadores de tumor reactivo (M3), a diferentes horas post-inyección, mostró una acumulación creciente en el tumor al cabo de 72 h, con captación en hígado y riñón. Se observó también que al aumentar la relación molar CA-DTPA se incrementó el porcentaje de radiactividad asociada al riñón, lo cual indicaría una mayor inestabilidad del radiofármaco