Changes in serum levels of TNF-α, IL-6, OPG, RANKL and their correlation with radiographic and clinical assessment in fragility fractures and high energy fractures

Stages of bone turnover during fracture repair can be assessed employing serum markers of osteoblastic and osteoclastic activity, inflammatory cytokines, clinical evaluation and imaging instruments. Our study compare the fracture healing process in fragility fractures and high energy fractures by evaluating serum changes of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG) and receptor activator of the nuclear factor-kB ligand (RANKL) in combination with radiographic (Radiographic Union Scale for Tibial fractures, RUST) and clinical (Lower extremity measure, LEM) assessments. We enrolled 56 patients divided into four corresponding groups: group A with high energy trauma fracture (tibial/femoral shaft); group B with low energy trauma fracture (femoral fractures); healthy (control A) and osteoporotic subjects (control B). Blood samples were collected before surgery (T0) and after 10 weeks (T10). Serum concentrations of IL-6, TNF-α, RANKL and OPG were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. Our results show that RANKL values are significantly higher at T10 than at T0 in low energy trauma fractures (group B). OPG is significantly lower in each control group than that of the respective fractured group and its concentration at T0 and at T10 is significantly lower in high than in low energy fractures. RANKL/OPG ratio is significantly higher in both controls than in fractured groups, and significantly increases after 10 weeks. IL-6 and TNF-α concentrations significantly decrease during fracture healing and are higher in high (group A) than in low energy fractures (group B). Significant differences were also found in both RUST score and LEM between groups A and B. Changes in TNF-α and IL-6 levels correlate with RUST and LEM in fragility and high energy fractures, while RANKL/OPG ratio is associated with these clinical parameters only in fragility fractures. These findings suggest that serum levels of IL-6, TNF-α, RANKL and OPG might be used to monitor the stages of fracture repair. Further studies will be needed to confirm the role of these cytokines in fracture repair

Coadministration of Atorvastatin Prevents Nitroglycerin-Induced Endothelial Dysfunction and Nitrate Tolerance in Healthy Humans

ObjectivesWe aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans.BackgroundAnimal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunction and tolerance, likely through an antioxidant mechanism.MethodsThirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 days. On the second visit, forearm blood flow was measured with venous-occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 μg/min). Acetylcholine infusions were coinfused first with saline, and repeated during the coinfusion of vitamin C (24 mg/min). Blood pressure responses to sublingual GTN (400 μg) were assessed on both visits.ResultsAcetylcholine responses in the GTN plus placebo group were significantly attenuated versus those in the GTN plus atorvastatin and atorvastatin groups (p < 0.01). Coinfusion of vitamin C completely restored acetylcholine responses in the GTN plus placebo group (p < 0.01 vs. saline coinfusion), but caused no change in either the atorvastatin or the GTN plus atorvastatin groups. Blood pressure responses to sublingual GTN did not significantly change between visits in subjects receiving GTN plus atorvastatin and atorvastatin alone, but were significantly blunted in the GTN plus placebo group (p < 0.05).ConclusionsThe present findings demonstrate, for the first time in humans, that atorvastatin prevents both GTN-induced endothelial dysfunction and nitrate tolerance, likely by counteracting the GTN-induced increase in oxidative stress

Pengendalian Frekuensi Dengan Menggunakan Kontrol Fuzzy Prediktif Pada Simulator Plant Turbin-Generator Pada PLTU

Sistem pembangkit dirasakan sangat perlu guna memenuhi kebutuhan tenaga listrik yang semakin meningkat, kestabilan sangat dibutuhkan pada proses pembangkit sehingga sistem pengendalian digunakan untuk menjaga variabel proses tersebut tetap stabil. Salah satunya adalah dengan melakukan pengendali frekuensi pada tubin-generator suatu pembangkit listik, contohnya PLTU (Pembangkit Listrik Tenaga Uap). Frekuensi dari turbin uap harus dijaga kestabilannya agar keluaran daya listrik di generator berjalan dengan baik. Fluktuasi frekuensi adalah salah satu kendala penyampaian daya listrik ke beban, juga waktu kembali yang tidak segera ke kondisi normal akan mengakibatkan kerusakan pada sistem seperti patahnya poros turbin-generator dan kemungkinan terjadi gangguan pada jaringan listrik, sehingga perlu dilakukan pengaturan laju aliran uap yang masuk ke turbin. Kontroler yang digunakan untuk menjaga Perubahan frekuensi adalah kontrol fuzzy prediktif, dengan penambahan gain K1 pada kontrol fuzzy prediktif sebesar 42.35 yang bekerja secara sucsessive kontroler ini dapat mengurangi error sebesar 1,04% jika sistem hanya menggunakan kontroler fuzzy pada saat terjadi Perubahan beban

UTRdb and UTRsite (RELEASE 2010) : a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs

The 5' and 3' untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5' and 3' untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated and also collated as the UTRsite database where more specific information on the functional motifs and cross-links to interacting regulatory protein are provided. In the current update, the UTR entries have been organized in a gene-centric structure to better visualize and retrieve 5' and 3'UTR variants generated by alternative initiation and termination of transcription and alternative splicing. Experimentally validated miRNA targets and conserved sequence elements are also annotated. The integration of UTRdb with genomic data has allowed the implementation of an efficient annotation system and a powerful retrieval resource for the selection and extraction of specific UTR subsets. All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://utrdb.ba.itb.cnr.it/

p53FamTaG: a database resource of human p53, p63 and p73 direct target genes combining in silico prediction and microarray data

<p>Abstract</p> <p>Background</p> <p>The p53 gene family consists of the three genes p53, p63 and p73, which have polyhedral non-overlapping functions in pivotal cellular processes such as DNA synthesis and repair, growth arrest, apoptosis, genome stability, angiogenesis, development and differentiation. These genes encode sequence-specific nuclear transcription factors that recognise the same responsive element (RE) in their target genes. Their inactivation or aberrant expression may determine tumour progression or developmental disease. The discovery of several protein isoforms with antagonistic roles, which are produced by the expression of different promoters and alternative splicing, widened the complexity of the scenario of the transcriptional network of the p53 family members. Therefore, the identification of the genes transactivated by p53 family members is crucial to understand the specific role for each gene in cell cycle regulation. We have combined a genome-wide computational search of p53 family REs and microarray analysis to identify new direct target genes. The huge amount of biological data produced has generated a critical need for bioinformatic tools able to manage and integrate such data and facilitate their retrieval and analysis.</p> <p>Description</p> <p>We have developed the p53FamTaG database (p53 FAMily TArget Genes), a modular relational database, which contains p53 family direct target genes selected in the human genome searching for the presence of the REs and the expression profile of these target genes obtained by microarray experiments. p53FamTaG database also contains annotations of publicly available databases and links to other experimental data.</p> <p>The genome-wide computational search of the REs was performed using PatSearch, a pattern-matching program implemented in the DNAfan tool. These data were integrated with the microarray results we produced from the overexpression of different isoforms of p53, p63 and p73 stably transfected in isogenic cell lines, allowing the comparative study of the transcriptional activity of all the proteins in the same cellular background.</p> <p>p53FamTaG database is available free at <url>http://www2.ba.itb.cnr.it/p53FamTaG/</url></p> <p>Conclusion</p> <p>p53FamTaG represents a unique integrated resource of human direct p53 family target genes that is extensively annotated and provides the users with an efficient query/retrieval system which displays the results of our microarray experiments and allows the export of RE sequences. The database was developed for supporting and integrating high-throughput <it>in silico</it> and experimental analyses and represents an important reference source of knowledge for research groups involved in the field of oncogenesis, apoptosis and cell cycle regulation.</p