Search results for " type II"
showing 10 items of 542 documents
Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity
2018
Significance In spite of TNF involvement in the pathogenesis of multiple sclerosis (MS), systemic TNF neutralization in MS patients was not successful. One of the possible reasons is that TNF possesses both pathogenic and protective features that may be related to TNFR1 versus TNFR2 receptor engagement. This study uncovers one of such protective functions of TNF mediated by intrinsic TNFR2 signaling in Treg cells. In mice bearing humanized TNF and TNFR2 genetic loci, TNFR2 ablation restricted to Treg cells led to reduced capacity to control Th17 cell responses, exacerbated experimental autoimmune encephalomyelitis (EAE) development, and affected the maintenance of Treg cells. These findings…
Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
2002
A series of nine dimethylamino-chalcone derivatives (1,3-diaryl-propenones) was synthesized and screened as potential inhibitors of NO and PGE(2) production in the RAW 264.7 macrophage cell line. 4-Dimethylamino-2',5'-dimethoxychalcone (6) was found to be the most potent and dual inhibitor (IC(50s) in the submicromolar range) of NO and PGE(2) production. 2',6'-Dimethoxylation appeared to be an effective requirement for selective and potent inhibition of nitric oxide synthase induction as it was confirmed by Western blot analysis. Chalcone (6) at 25 mg kg(-1) by oral route, inhibited significantly the formation of oedema in the carrageenan-induced model of inflammation in mice.
Retinol encapsulated into amorphous Ca2+ polyphosphate nanospheres acts synergistically in MC3T3-E1 cells
2015
Both the quality and quantity of collagen, the major structural component of the skin, decrease in aging skin. We succeeded to encapsulate retinol into amorphous inorganic polyphosphate (polyP) nanoparticles together with calcium ions ("aCa-polyP-NP"), under formation of amorphous Ca-polyP/retinol nanospheres ("retinol/aCa-polyP-NS"). The globular nanospheres are not cytotoxic, show an almost uniform size of ≈ 45 nm and have a retinol content of around 25%. Both components of those nanospheres, retinol and the aCa-polyP-NP, if administered together, caused a strong increase in proliferation of mouse calvaria MC3T3 cells. The expressions of collagen types I, II and III genes, but not the exp…
New insights in the metabolic behaviour of PAO under negligible poly-P reserves
2017
[EN] In a previous study the authors confirmed the ability of PAOs to perform GAO metabolism in short-term experiments. However, what happens when PAOs are exposed to poly-P shortage for an extended period of time? The answer to this question was the aim of this work from a macroscopic and microscopic point of view. Therefore, the poly-P was removed from a PAO enriched SBR and maintained without poly-P during five solid retention time. The PAOs were found to quickly change their metabolism to a clear GAO performance and remained without GAO colonization for the entire experimental period, even though GAO was present (around 5%) at the beginning of the experiment. Unlike the results obtained…
Plasma non-cholesterol sterols: a useful diagnostic tool in pediatric hypercholesterolemia.
2010
Current guidelines strongly recommend the identification of genetic forms of hypercholesterolemia (HC) during childhood. The usefulness of non–cholesterol sterols (NCS) in the diagnosis of genetic HC has not been fully explored. Plasma NCS were measured by gas chromatography/mass spectrometry (GC/MS) in 113 children with hypercholesterolemia affected by: autosomal dominant hypercholesterolemia (ADH), familial combined hyperlipidemia (FCHL), polygenic hypercholesterolemia (PHC), and in 79 controls to evaluate: i) plasma NCS profile in different genetic HC and ii) the usefulness of NCS for the diagnosis of HC beyond current clinical criteria. ADH was characterized by raised lathosterol/total …
Electrothermal Atomic Absorption Spectrometric Diagnosis of Familial Hypercholesterolemia
2000
We have developed a new nonradioactive assay to identify human low-density lipoprotein receptor defects. It is based on the incubation of cultured cells with colloidal gold-LDL conjugates and quantitation of the gold associated with the cells by electrothermal atomic absorption spectrometry. After an oxidative treatment with nitric and hydrochloric acids, the biological matrix interferes neither with the gold recovery nor with the gold measurements, which are linear, at least from 0.15 to 3 ng of gold. When cells expressing a functional LDL receptor are incubated with increasing amounts of colloidal-gold LDL conjugates, the obtained saturation curve parallels that described when [125I]LDL i…
Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization
2006
Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) tha…
Adaptive trial design: a general methodology for censored time to event data.
2008
Adaptive designs allow a clinical trial design to be changed according to interim findings without inflating type I error. The Inverse Normal method can be considered as an adaptive generalization of classical group sequential designs. The use of the Inverse Normal method for censored survival data was demonstrated only for the logrank statistic. However, the logrank statistic is inefficient in the presence of nuisance covariates affecting survival. We demonstrate, how the Inverse Normal method can be applied to Cox regression analysis. The required independence between test statistics of the different stages of the trial can be obtained by two different approaches. One is using the indepen…
Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients
2022
Background and aims: Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study. Methods: 836 hypercholesterolemic patients with LDL-C > 4.…
Familial hypercholesterolæmia in children and adolescents: Gaining decades of life by optimizing detection and treatment
2015
Contains fulltext : 155263.pdf (Publisher’s version ) (Open Access) Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testin…