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93.
Nicole Willems Frances C Bach Saskia G M Plomp Mattie HP van Rijen Jeannette Wolfswinkel Guy CM Grinwis Clemens Bos Gustav J Strijkers Wouter JA Dhert Bj?rn P Meij Laura B Creemers Marianna A Tryfonidou 《Arthritis research & therapy》2015,17(1)
IntroductionStrategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain.MethodsCanine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue.ResultsIn vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7.ConclusionsAn intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users. 相似文献94.
Loes?AM?Leenen Ben?FM?WijnenEmail author Reina?JA?de Kinderen Marian?HJM?Majoie Caroline?M?van Heugten Silvia?MAA?Evers 《BMC neurology》2014,14(1):255
Background
In patients with epilepsy, poor adherence to anti-epileptic drugs has been shown to be the most important cause of poorly controlled epilepsy. Furthermore, it has been noted that the quality of life among patients with epilepsy can be improved by counseling and treatments aimed at increasing their self-efficacy and concordance, thus stimulating self-management skills. However, there is a need for evidence on the effectiveness of such programs, especially within epilepsy care. Therefore, we have developed a multi-component intervention (MCI) which combines a self-management/education program with e-Health interventions. Accordingly, the overall objective of this study is to assess the (cost)-effectiveness and feasibility of the MCI, aiming to improve self-efficacy and concordance in patients with epilepsy.Methods
A RCT in two parallel groups will be conducted to compare the MCI with a control condition in epilepsy patients. One hundred eligible epilepsy patients will be recruited and allocated to either the intervention or control group. The intervention group will receive the MCI consisting of a self-management/education program of six meetings, including e-Health interventions, and will be followed for 12 months. The control group will receive care as usual and will be followed for 6 months, after which patients will be offered the possibility of participating in the MCI. The study will consist of three parts: 1) a clinical effectiveness study, 2) a cost-effectiveness study, and 3) process evaluation. The primary outcome will be self-efficacy. Secondary outcomes include adherence, side effects, change in seizure severity & frequency, improved quality of life, proactive coping, and societal costs. Outcome assessments will be done using questionnaires at baseline and after 3, 6, 9, and 12 months (last two applicable only for intervention group).Discussion
In times of budget constraints, MCI could be a valuable addition to the current healthcare provision for epilepsy, as it is expected that higher concordance and self-efficacy will result in reduced use of healthcare resources and an increased QOL. Accordingly, this study is aimed helping patients to be their own provider of health care, shifting epilepsy management from professionals to self-care by patients equipped with appropriate skills and tools.Trial registration number
NTR4484.95.
López-Valenzuela BE Armenta-Bojórquez AD Hernández-Verdugo S Apodaca- Sánchez MA Samaniego-Gaxiola JA Valdez-Ortiz A 《Phyton》2019,88(1):37-46
Microbes that are beneficial to plants are used to
enhance the crop growth, yield and are alternatives to chemical
fertilizers. Trichoderma and Bacillus are the predominant plant
growth-promoting fungi and bacteria. The objective of this study
was select, characterize, and evaluate isolates of Trichoderma
spp. and Bacillus spp. native from the northern region of Sinaloa,
Mexico, and assess their effect on growth promotion in maize (Zea
mays L.). In greenhouse conditions, four Trichoderma isolates and
twenty Bacillus isolates, as well as two controls, were tested in a
completely randomized design with three replicates. We selected
the two best strains of Trichoderma and Bacillus: TB = Trichoderma
asperellum, TF = Trichoderma virens, B14 = Bacillus cereus sensu
lato and B17 = Bacillus cereus, which were evaluated in the field in
a completely randomized blocks in factorial arrangement design
with three replicates applying different rates of nitrogen fertilizer
(0, 150 kg N/ha, and 300 kg N/ha). Treatments 5 (B17 = B. cereus)
and 11 (TF = T. virens) both fertilized with 150 kg N/ha showed
similar yields and they did not reveal significant differences from
the treatments fertilized with 300 kg N/ha. This indicated that
treatment 5 (B17= B. cereus with 150 kg N/ha) and treatment
11 (TF= T. virens with 150 kg N/ha) were efficient as growth
promoters, by not showing significant differences in root volume
and dry weight of foliage. The results indicated a reduction of 50%
in the rate of nitrogen to fertilizer required for maize (Zea mays
L.) crops. These microorganisms Trichoderma and Bacillus could
be an alternative to reduce the use of chemical fertilizers in maize. 相似文献
96.
I Prieto-Potín JA Roman-Blas MJ Martínez-Calatrava R Gómez R Largo Gabriel Herrero-Beaumont 《Arthritis research & therapy》2013,15(4):R81
Objective
The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.Methods
Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-α and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone.Results
Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-α and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups.Conclusions
This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process. 相似文献97.
Adel Shalata Maria?C. Ramirez Robert?J. Desnick Nolan Priedigkeit Christoph Buettner Claudia Lindtner Mohammed Mahroum Muhammad Abdul-Ghani Feng Dong Nazik Arar Olga Camacho-Vanegas Rui Zhang Sandra?C. Camacho Ying Chen Mwafaq Ibdah Ralph DeFronzo Virginia Gillespie Kevin Kelley Brian?D. Dynlacht Sehyun Kim Marc?J. Glucksman Zvi?U. Borochowitz John?A. Martignetti 《American journal of human genetics》2013,93(6):1061-1071
Obesity is a major public health concern, and complementary research strategies have been directed toward the identification of the underlying causative gene mutations that affect the normal pathways and networks that regulate energy balance. Here, we describe an autosomal-recessive morbid-obesity syndrome and identify the disease-causing gene defect. The average body mass index of affected family members was 48.7 (range = 36.7–61.0), and all had features of the metabolic syndrome. Homozygosity mapping localized the disease locus to a region in 3q29; we designated this region the morbid obesity 1 (MO1) locus. Sequence analysis identified a homozygous nonsense mutation in CEP19, the gene encoding the ciliary protein CEP19, in all affected family members. CEP19 is highly conserved in vertebrates and invertebrates, is expressed in multiple tissues, and localizes to the centrosome and primary cilia. Homozygous Cep19-knockout mice were morbidly obese, hyperphagic, glucose intolerant, and insulin resistant. Thus, loss of the ciliary protein CEP19 in humans and mice causes morbid obesity and defines a target for investigating the molecular pathogenesis of this disease and potential treatments for obesity and malnutrition. 相似文献
98.
Sacha?Ferdinandusse Hans?R?Waterham Simon?JR?Heales Garry?K?Brown Iain?P?Hargreaves Jan-Willem?Taanman Roxana?Gunny Lara?Abulhoul Ronald?JA?Wanders Peter?T?Clayton James?V?Leonard Shamima?RahmanEmail author 《Orphanet journal of rare diseases》2013,8(1):188
Background
Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme deficiencies can arise from a number of mechanisms, including defective maintenance or expression of mitochondrial DNA. Impaired biosynthesis of iron-sulphur clusters and lipoic acid can lead to pyruvate dehydrogenase complex (PDHc) deficiency in addition to multiple RC deficiencies, known as the multiple mitochondrial dysfunctions syndrome.Methods
Two brothers born to distantly related Pakistani parents presenting in early infancy with a progressive neurodegenerative disorder, associated with basal ganglia changes on brain magnetic resonance imaging, were investigated for suspected Leigh-like mitochondrial disease. The index case had deficiencies of multiple RC enzymes and PDHc in skeletal muscle and fibroblasts respectively, but these were normal in his younger brother. The observation of persistently elevated hydroxy-C4-carnitine levels in the younger brother led to suspicion of HIBCH deficiency, which was investigated by biochemical assay in cultured skin fibroblasts and molecular genetic analysis.Results
Specific spectrophotometric enzyme assay revealed HIBCH activity to be below detectable limits in cultured skin fibroblasts from both brothers. Direct Sanger sequence analysis demonstrated a novel homozygous pathogenic missense mutation c.950G <A; p.Gly317Glu in the HIBCH gene, which segregated with infantile-onset neurodegeneration within the family.Conclusions
HIBCH deficiency, a disorder of valine catabolism, is a novel cause of the multiple mitochondrial dysfunctions syndrome, and should be considered in the differential diagnosis of patients presenting with multiple RC deficiencies and/or pyruvate dehydrogenase deficiency.99.
A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony 总被引:24,自引:1,他引:23
The method of evolutionary parsimony--or operator invariants--is a
technique of nucleic acid sequence analysis related to parsimony analysis
and explicitly designed for determining evolutionary relationships among
four distantly related taxa. The method is independent of substitution
rates because it is derived from consideration of the group properties of
substitution operators rather than from an analysis of the probabilities of
substitution in branches of a tree. In both parsimony and evolutionary
parsimony, three patterns of nucleotide substitution are associated
one-to-one with the three topologically linked trees for four taxa. In
evolutionary parsimony, the three quantities are operator invariants. These
invariants are the remnants of substitutions that have occurred in the
interior branch of the tree and are analogous to the substitutions assigned
to the central branch by parsimony. The two invariants associated with the
incorrect trees must equal zero (statistically), whereas only the correct
tree can have a nonzero invariant. The chi 2-test is used to ascertain the
nonzero invariant and the statistically favored tree. Examples, obtained
using data calculated with evolutionary rates and branchings designed to
camouflage the true tree, show that the method accurately predicts the
tree, even when substitution rates differ greatly in neighboring peripheral
branches (conditions under which parsimony will consistently fail). As the
number of substitutions in peripheral branches becomes fewer, the parsimony
and the evolutionary-parsimony solutions converge. The method is robust and
easy to use.
相似文献
100.