scholarly journals A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn’s Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhoulei Li ◽  
Baolan Lu ◽  
Jinjiang Lin ◽  
Shaofu He ◽  
Li Huang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mr Imaging ◽  
Rat Model ◽  
Type I Collagen ◽  
Type I ◽  
Imaging Probe ◽  
Antifibrotic Therapy ◽  
Before And After ◽  
Targeted Mri

Fibrostenosis is a serious complication of Crohn’s disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T1 relaxation time (T1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson’s trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p < 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.

scholarly journals CM-101: Type I Collagen–targeted MR Imaging Probe for Detection of Liver Fibrosis

Radiology ◽  
2018 ◽  
Vol 287 (2) ◽  
pp. 581-589 ◽  
Author(s):  
Christian T. Farrar ◽  
Eric M. Gale ◽  
Richard Kennan ◽  
Ian Ramsay ◽  
Ricard Masia ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mr Imaging ◽  
Type I Collagen ◽  
Type I ◽  
Imaging Probe

Transabdominal bowel sonography modifications in patients with active Crohn's disease before and after infliximab treatment

2001 ◽  
Vol 120 (5) ◽  
pp. A273-A273
Author(s):  
C SERRA ◽  
P GIONCHETTI ◽  
L VOLPE ◽  
C MORELLI ◽  
M CAMPIERI ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Infliximab Treatment ◽  
Before And After ◽  
Bowel Sonography

scholarly journals Targeting Mitochondrial Damage as a Therapeutic for Ileal Crohn’s Disease

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1349
Author(s):  
Kibrom M. Alula ◽  
Dakota N. Jackson ◽  
Andrew D. Smith ◽  
Daniel S. Kim ◽  
Kevin Turner ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Lipid Metabolism ◽  
Crohn's Disease ◽  
Paneth Cell ◽  
Mitochondrial Damage ◽  
Paneth Cells ◽  
Cell Phenotype ◽  
Type I ◽  
Targeted Therapeutics ◽  
Gene Signatures

Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction in Paneth cells as a mediator of ileitis in mice. We hypothesized that CD Paneth cells exhibit impaired mitochondrial health and that mitochondrial-targeted therapeutics may provide a novel strategy for ileal CD. Terminal ileal mucosal biopsies from adult CD and non-IBD patients were characterized for Paneth cell phenotyping and mitochondrial damage. To demonstrate the response of mitochondrial-targeted therapeutics in CD, biopsies were treated with vehicle or Mito-Tempo, a mitochondrial-targeted antioxidant, and RNA transcriptome was analyzed. During active CD inflammation, the epithelium exhibited mitochondrial damage evident in Paneth cells, goblet cells, and enterocytes. Independent of inflammation, Paneth cells in Type I CD patients exhibited mitochondrial damage. Mito-Tempo normalized the expression of interleukin (IL)-17/IL-23, lipid metabolism, and apoptotic gene signatures in CD patients to non-IBD levels. When stratified by Paneth cell phenotype, the global tissue response to Mito-Tempo in Type I patients was associated with innate immune, lipid metabolism, and G protein-coupled receptor (GPCR) gene signatures. Targeting impaired mitochondria as an underlying contributor to inflammation provides a novel treatment approach for CD.

scholarly journals Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Sanchis-Artero ◽  
Juan Francisco Martínez-Blanch ◽  
Sergio Manresa-Vera ◽  
Ernesto Cortés-Castell ◽  
Marina Valls-Gandia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Area Under The Curve ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Multicenter Observational Study ◽  
Partial Restoration ◽  
Before And After

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

scholarly journals Musculoskeletal Outcomes from Chronic High-Speed, High-Impulse Resistance Exercise

2018 ◽  
Vol 39 (10) ◽  
pp. 791-801 ◽  
Author(s):  
John Caruso ◽  
Michael Voor ◽  
Jason Jaggers ◽  
T. Symons ◽  
Jeremy Stith ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
High Speed ◽  
Type I Collagen ◽  
Training Session ◽  
Knee Extension ◽  
Type I ◽  
Before And After ◽  
Force Peak ◽  
Blood Marker ◽  
Hip Extension

AbstractWhile bones and muscles adapt to mechanical loading, it appears that very specific types of stimuli must be applied to achieve osteogenesis. Our study assessed musculoskeletal outcomes to 30 training sessions on an Inertial Exercise Trainer (Newnan, GA). Subjects (n=13) performed workouts with their left leg, while their right served as an untreated control. Workouts entailed three 60-s sets each of knee extension, hip extension and calf press exercises, separated by 90-s rests. Before and after the 30 training sessions, subjects underwent strength tests (knee and ankle extensors of both legs), DEXA scans (hip, knee and ankles of both legs), and blood draws. After 30 training sessions 2×2 ANOVAs showed left leg peak torques rose significantly. 2×2 ANCOVAs, with bone scan area as a covariate, showed significant left leg calcaneal bone mineral content (+29%) and density (+33%) increases after 30 training sessions. A significant decline in C-terminal telopeptides of type I collagen, a blood marker of bone resorption, also occurred after 30 training sessions. The Inertial Exercise Trainer’s large volume of training session repetitions elicited high peak force, peak acceleration and impulses that likely provided a mechanical loading stimulus that evoked calcaneal accretion.

Platelet deposition on stainless steel, spiral, and braided polylactide stents

2004 ◽  
Vol 92 (12) ◽  
pp. 1394-1401 ◽  
Author(s):  
Paula Maasilta ◽  
Hanne Juuti ◽  
Juha-Pekka Nuutinen ◽  
Ari Harjula ◽  
Ulla-Stina Salminen ◽  
...  
Keyword(s):  
Stainless Steel ◽  
Flow Rate ◽  
Type I Collagen ◽  
Blood Perfusion ◽  
Type I ◽  
Thrombotic Occlusion ◽  
Protein Deposition ◽  
Biodegradable Stents ◽  
Platelet Deposition ◽  
Before And After

SummaryPlatelets play a key role in (sub)acute thrombotic occlusion after stenting. We examined the possible differences between biodegradable polylactide (PLA) and stainless steel (SS) stents in platelet attachment and morphology after whole blood perfusion. PLA stents of different configurations (spiral/braided) and polycaprolactone-polylactide (PCL-PLA)-coatings, or SS stents were implanted into a PVC tube (Ø 3.2 mm), with or without precoating of the tube with type-I collagen. PPACK (30 µM)-anticoagulated blood with 3H-serotonin prelabeled platelets was perfused (flow rate: 30 ml/min, 90 s) over the stents. Platelet deposition was assessed by scintillation counting and morphology by scanning electron microscopy (SEM). To examine coagulation activation, plasma prothrombin fragments (F1+2) were measured before and after the perfusion. Protein deposition on PLA/SS stents was assessed at augmented shear forces mimicking coronary flow (rate: 60 ml/min, 60 s) under minimal anticoagulation (PPACK 1 µM). More platelets deposited on PLA stents than on SS stents under all study conditions (p <0.03). Under anticoagulation (PPACK 30 µM) the generation of F1+2 remained unaltered. Under higher flow rate and limited anticoagulation SS stents accumulated 3.27 ± 0.75 µg and PLA stents 5.25 ± 1.74 µg of protein (Mean ± SD, p <0.95). Among all biodegradable stents, the braided PLA stent coated with PCL-PLA-heparin accumulated the fewest platelets (p <0.02). In SEM, signs of platelet activation on braided heparin-coated PLA stents, when compared with uncoated braided PLA/SS stents, appeared modest. In conclusion, PCL-PLAheparin coating of biodegradable stents may enhance their hemocompatibility, expressed by less platelet deposition. Nevertheless, materials, design, and coating techniques of biodegradable stents must be further developed.

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