Objective: To study the concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocytes (ASTLL) and ileocolonoscopy in patients with spondyloarthropathies (SpA) and without clinical evidence of inflammatory bowel disease (IBD).
Patients And Methods: Fifteen patients with SpA (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD were studied prospectively with ASTLL and ileocolonoscopy.
Results: This cohort consisted of seven men and eight women aged 31.8+/-10.5 yr (18-47) [mean age +/- S.D. (range)] and with a disease duration of 6.0+/-4.4 yr (0.4-15). ASTLL showed abnormal uptake in four patients. Ileocolonoscopy was abnormal in five patients, showing acute inflammatory lesions in one patient with reactive arthritis, undifferentiated chronic inflammatory lesions in two cases, and features indistinguishable from those of Crohn's disease in two cases. ASTLL was negative in two cases in which ileocolonoscopy showed inflammatory lesions and was positive (terminal ileum) in one case with normal ileocolonoscopy. The concordance between the two examinations was statistically significant (kappa = 0.53; P = 0.008).
Conclusion: ASTLL may be an interesting tool to detect subclinical gut inflammation in patients with SpA.
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http://dx.doi.org/10.1093/rheumatology/38.6.543 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, Netherlands.
The lack of an in-vivo pathology marker for synuclein pathology has been a long standing challenge for dementia for Lewy bodies (DLB) research. This issue is critically important for phase II trials, which are often small, requiring the precise measurement of the biological effects, whether disease modifying or symptomatic. Recent advances have enabled the determination of alpha-synuclein pathology status with CSF measurements, using aggregation assays [RT-QUIC].
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Alzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
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