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2.
Sci Rep ; 7(1): 17888, 2017 12 20.
Article in English | MEDLINE | ID: mdl-29263366

ABSTRACT

Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients.


Subject(s)
Biomarkers/blood , Matrix Metalloproteinase 9/blood , Muscular Dystrophy, Duchenne/blood , Muscular Dystrophy, Duchenne/genetics , Oligonucleotides, Antisense/genetics , Adolescent , Adult , Child , Child, Preschool , Clinical Trials, Phase III as Topic , Double-Blind Method , Dystrophin/genetics , Exons/genetics , Female , Humans , Longitudinal Studies , Male , Randomized Controlled Trials as Topic , Young Adult
3.
Allergy ; 66(7): 934-40, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21261659

ABSTRACT

BACKGROUND: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. METHODS: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. RESULTS: The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease. CONCLUSION: Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.


Subject(s)
Dermatitis, Atopic/physiopathology , Intermediate Filament Proteins/genetics , Pyrrolidonecarboxylic Acid/metabolism , Severity of Illness Index , Skin/metabolism , Urocanic Acid/metabolism , Child , Child, Preschool , Dermatitis, Atopic/genetics , Dermatitis, Atopic/metabolism , Female , Filaggrin Proteins , Genetic Predisposition to Disease , Genotype , Humans , Intermediate Filament Proteins/metabolism , Male , Mutation
4.
Asia Pac J Clin Nutr ; 18(4): 546-8, 2009.
Article in English | MEDLINE | ID: mdl-19965346

ABSTRACT

In addition to product trade, technology trade has become one of the alternatives for globalization action around the world. Although not all technologies employed on the technology trade platform are innovative technologies, the data base of international technology trade still is a good indicator for observing innovative technologies around world. The technology trade data base from Sinew Consulting Group (SCG) Ltd. was employed as an example to lead the discussion on security or safety issues that may be caused by these innovative technologies. More technologies related to processing, functional ingredients and quality control technology of food were found in the data base of international technology trade platform. The review was conducted by categorizing technologies into the following subcategories in terms of safety and security issues: (1) agricultural materials/ingredients, (2) processing/engineering, (3) additives, (4) packaging/logistics, (5) functional ingredients, (6) miscellaneous (include detection technology). The author discusses examples listed for each subcategory, including GMO technology, nanotechnology, Chinese medicine based functional ingredients, as well as several innovative technologies. Currently, generation of innovative technology advance at a greater pace due to cross-area research and development activities. At the same time, more attention needs to be placed on the employment of these innovative technologies.


Subject(s)
Agriculture/methods , Food Contamination , Food Industry/methods , Food Supply , Animals , Food Contamination/prevention & control , Humans , Internationality , Nutrition Policy
5.
Br J Biomed Sci ; 58(4): 207-11, 2001.
Article in English | MEDLINE | ID: mdl-11787995

ABSTRACT

Evaluation and introduction of a chromogenic urinary tract infection (UTI) medium for the primary culture of routine urine specimens in a very large clinical microbiology laboratory is described. A modified scheme for the direct identification of the main groups of organisms causing UTI has led to quality improvements, with enhanced discrimination of mixed cultures and in efficiencies in staffing and working time that counterbalance increases in media costs. These improvements, together with the concurrent introduction of boric acid preservative for specimens from general practice, significantly reduced the level of positive results by 4.6% (2383 specimens) over an eight-month period (P <0.001). Chromogenic medium provided a reliable alternative to CLED medium for the routine culture of urine specimens.


Subject(s)
Bacteriuria/diagnosis , Chromogenic Compounds , Bacteriological Techniques , Boric Acids , Culture Media , Humans
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