scholarly journals Effect of serotonin modulation on dystrophin-deficient zebrafish

Biology Open ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. bio053363 ◽  
Author(s):  
Janelle M. Spinazzola ◽  
Matthias R. Lambert ◽  
Devin E. Gibbs ◽  
James R. Conner ◽  
Georgia L. Krikorian ◽  
...  

ABSTRACTDuchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and re-application of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies.

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3157
Author(s):  
Adiba I. Azad ◽  
Charles B. Rosen ◽  
Timucin Taner ◽  
Julie K. Heimbach ◽  
Gregory J. Gores

Selected patients with unresectable perihilar cholangiocarcinoma (pCCA) derive long-term benefits from liver transplantation. Between 1993–2019, our group at Mayo Clinic performed 237 transplants for pCCA. With this experience, we note that two distinct patient populations comprise this group of pCCA patients: those with underlying primary sclerosing cholangitis (PSC) and those without identifiable risk factors termed sporadic or de novo pCCA. Long-term survival after transplant is better in PSC patients (74% five-year survival) than in those with de novo pCCA (58% five-year survival). Herein, we review the likely clinical factors contributing to the divergence in outcomes for these two patient populations. We also offer our insights on how further advances may improve patient selection and survival, focusing on the de novo pCCA patient population.


2002 ◽  
Vol 36 (4) ◽  
pp. 707-712 ◽  
Author(s):  
Lisa J Miller ◽  
Kristy L Kubes

OBJECTIVE: T o evaluate literature that discusses the treatment of fibromyalgia syndrome (FMS) with agents that involve the neurotransmitter serotonin. DATA SOURCES: Biomedical literature accessed through MEDLINE (1966–August 2001) and International Pharmaceutical Abstracts. DATA SYNTHESIS: The cause and pathophysiology of FMS remain elusive, although abnormalities in the serotonin pathway have been implicated. Several serotonergic agents have been studied for use in FMS. Trials and case reports focusing on the use of newer agents: the selective serotonin reuptake inhibitors, venlafaxine and tramadol, were reviewed. CONCLUSIONS: Current research suggests that the serotonergic agents may reduce at least some of the symptoms of FMS. However, medications that act on multiple neurotransmitters may prove to be more effective in symptom management. Additional long-term studies are required in order to validate these results.


2002 ◽  
Vol 38 ◽  
pp. 9-19 ◽  
Author(s):  
Guy S Salvesen

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.


2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A747-A748
Author(s):  
S DRESNER ◽  
A IMMMANUEL ◽  
P LAMB ◽  
S GRIFFIN

2006 ◽  
Vol 175 (4S) ◽  
pp. 355-355
Author(s):  
Manuel Eisenberg ◽  
John S. Lam ◽  
Rakhee H. Goel ◽  
Allan J. Pantuck ◽  
Robert A. Figlin ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document