Improving access by delivering the 18 weeks referral to treatment target (RTT)

2008 ◽  
Keyword(s):  
Treatment Target

FRI0076 Low Disease Activity or DAS-Remission as Treatment Target in Early Rheumatoid Arthritis Patients

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 454.1-454
Author(s):  
G. Akdemir ◽  
I.M. Markusse ◽  
A.A. Schouffoer ◽  
P.B. de Sonnaville ◽  
B.A. Grillet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Treatment Target ◽  
Low Disease Activity

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target

2017 ◽  
Vol 26 (5) ◽  
pp. 442-449 ◽  
Author(s):  
Ahmed M. Selim ◽  
Nitasha Sarswat ◽  
Iosif Kelesidis ◽  
Muhammad Iqbal ◽  
Ramesh Chandra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Potential Treatment ◽  
Treatment Target ◽  
Plasma Serotonin

scholarly journals Avolition as the core negative symptom in schizophrenia: relevance to pharmacological treatment development

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gregory P. Strauss ◽  
Lisa A. Bartolomeo ◽  
Philip D. Harvey
Keyword(s):  
Negative Symptom ◽  
Negative Symptoms ◽  
Clinical Trial Design ◽  
Core Component ◽  
Treatment Target ◽  
Global Improvement ◽  
Treatment Development ◽  
The Core ◽  
Current Review ◽  
Symptom Domains

AbstractNegative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed.

scholarly journals Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Endocrinology ◽  
2018 ◽  
Vol 159 (8) ◽  
pp. 2836-2849 ◽  
Author(s):  
Vasileios Chortis ◽  
Angela E Taylor ◽  
Craig L Doig ◽  
Mark D Walsh ◽  
Eirini Meimaridou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adrenocortical Carcinoma ◽  
Reduced Form ◽  
Polyamine Metabolism ◽  
Metabolome Analysis ◽  
Nucleotide Synthesis ◽  
Treatment Target ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Response To Chemotherapy

Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.

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