scholarly journals The Role of Methotrexate in Psoriatic Therapy in the Age of Biologic and Biosimilar Medication: Therapeutic Benefits versus Toxicology Emergencies

Author(s):  
Carolina Negrei ◽  
Daniel Boda
Keyword(s):  
2021 ◽  
pp. 216770262199831
Author(s):  
Alex Lau-Zhu ◽  
Richard N. Henson ◽  
Emily A. Holmes

Intrusive memories of a traumatic event can be reduced by a subsequent interference procedure, seemingly sparing voluntary memory for that event. This selective-interference effect has potential therapeutic benefits (e.g., for emotional disorders) and legal importance (e.g., for witness testimony). However, the measurements of intrusive memory and voluntary memory typically differ in the role of associations between a cue and the emotional memory “hotspots.” To test this, we asked participants to watch a traumatic film followed by either an interference procedure (reminder plus Tetris) or control procedure (reminder only). Measurement of intrusions (using a laboratory task) and voluntary memory (recognition for film stills) were crossed with the presence or absence of associative cues. The reminder-plus-Tetris group exhibited fewer intrusions despite comparable recognition memory, replicating the results of prior studies. Note that this selective interference did not appear to depend on associative cues. This involuntary versus voluntary memory dissociation for emotional material further supports separate-trace memory theories and has applied advantages.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 447
Author(s):  
Richard B. Kreider ◽  
Jeffery R. Stout

Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.


2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Lakshana Sreenivasan ◽  
Hui Wang ◽  
Shyong Quin Yap ◽  
Pascal Leclair ◽  
Anthony Tam ◽  
...  

AbstractMedulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6789
Author(s):  
Misael Bermúdez-Bazán ◽  
Gustavo Adolfo Castillo-Herrera ◽  
Judith Esmeralda Urias-Silvas ◽  
Antonio Escobedo-Reyes ◽  
Mirna Estarrón-Espinosa

Agaves are plants used in the production of alcoholic beverages and fibers. Ever since ancient times, pre-Hispanic cultures in Mexico have used them in traditional medicine to cure different ailments. Over the years, studies of the active principles responsible for the therapeutic benefits of agaves have increased. Leaves and fibers are the main agro-wastes generated in tequila and mezcal production, while fibers are the main waste product in the textile sector. Different investigations have referred to the agro-waste from agave processing as a source of bioactive molecules called secondary metabolites (SM). Among them, phenols, flavonoids, phytosterols, and saponins have been extracted, identified, and isolated from these plants. The role of these molecules in pest control and the prospect of metabolites with the biological potential to develop novel drugs for chronic and acute diseases represent new opportunities to add value to these agro-wastes. This review aims to update the biological activities and recent applications of the secondary metabolites of the genus Agave.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Bryan S Yung ◽  
Sunny Y Xiang ◽  
Nicole Purcell ◽  
Hugh Rosen ◽  
Jerold Chun ◽  
...  

Sphingosine-1-phoshpate (S1P) is a bioactive lysophospholipid, generated and released at sites of tissue injury. S1P signals through a variety of G-protein coupled receptor subtypes and there are three major sub-types, S1P 1 , S1P 2 , and S1P 3 , to mediate cardiovascular responses. S1P 2 and S1P 3 receptors couple to Gα i , Gα 12 , Gα 13 and Gα q and we first examined the contribution of S1P 2 and S1P 3 to cardiac hypertrophy using S1P 2 and S1P 3 knockout (KO) mice and found that there is no difference in hypertrophy induced by pressure-overload. We previously showed that S1P provides cardioprotection against oxidative stress such as ischemia/reperfusion in which RhoA activation and its downstream effector PKD1 play an important role. It has not, however, been determined which S1P receptor subtype is responsible for S1P mediated cardioprotection. We knocked down the three major S1P receptors using siRNA in neonatal rat ventricular myocytes (NRVMs) and assessed RhoA and PKD1 activation induced by S1P. Knockdown of S1P 3 abolished RhoA activation and largely attenuated phosphorylation of PKD1 while knockdown of S1P 1 and S1P 2 did not. Using siRNA or pertussis toxin to inhibit different G-proteins, we further established that S1P regulates RhoA activation through Gα 13 , but not Gα 12 , Gα q , or Gα i . To investigate the role of S1P 3 receptors in the adult heart, hearts were isolated from wild-type or S1P 3 KO adult mice, perfused in the Langendorff mode and subjected to ex vivo ischemia/reperfusion. As previously reported, S1P perfusion significantly reduced infarct size induced by ischemia/reperfusion in WT hearts (by 50%), but this protection was abolished in the S1P 3 KO mouse heart. To further confirm the role of S1P 3 in cardioprotection we perfused WT mouse hearts with an S1P 3 -specific agonist CYM-51736. We observed that CYM-51736 attenuated the infarct size to a similar degree as that observed with S1P. Our findings reveal that activation of the S1P 3 receptor coupling to Gα 13 and subsequent RhoA activation is responsible for cardioprotection against ischemia/reperfusion. Accordingly specific drug targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease without the undesirable effects of global activation of other cardiac S1P receptors.


Author(s):  
Mark Griffiths ◽  
Daria J. Kuss ◽  
Angelica B. Ortiz de Gortari

There is a long history of using videogames in a therapeutic capacity, including rehabilitation for stroke patients, people with traumatic brain injuries, burns victims, wheelchair users, Erb’s palsy sufferers, children undergoing chemotherapy, children with muscular dystrophy, and autistic children. This chapter briefly examines a number of areas including: (1) videogames as physiotherapy and occupational therapy, (2) videogames as distractors in the role of pain management, (3) videogames and cognitive rehabilitation, (4) videogames and the development of social and communication skills among the learning disabled, (5) videogames and impulsivity/attention deficit disorders, (6) videogames and therapeutic benefits in the elderly, (7) videogames in psychotherapeutic settings, (8) videogames and health care, and (9) videogames and anxiety disorders. It is concluded that there has been considerable success when games are designed to address a specific problem or to teach a certain skill. However, generalizability outside the game-playing situation remains an important consideration.


2020 ◽  
Vol 319 (4) ◽  
pp. L596-L602
Author(s):  
Rodrigo Pacheco Silva-Aguiar ◽  
Diogo Barros Peruchetti ◽  
Patricia Rieken Macedo Rocco ◽  
Alvin H. Schmaier ◽  
Patrícia Machado Rodrigues e Silva ◽  
...  

A new form of severe acute respiratory syndrome (SARS) caused by SARS-coronavirus 2 (CoV-2), called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (ANG II) is linked to the pathogenesis of COVID-19. This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of ANG II. Furthermore, ANG II has a critical role in the genesis and worsening of hypertension. In this context, the idea that there is a surge in the level of ANG II with COVID-19 infection, causing multiple organ injuries in hypertensive patients becomes attractive. However, the role of other components of the renin angiotensin system (RAS) in this scenario requires elucidation. The identification of other RAS components in COVID-19 hypertension may provide both diagnostic and therapeutic benefits. Here, we summarize the pathophysiologic contributions of different components of RAS in hypertension and their possible correlation with poor outcome observed in hypertensive patients with COVID-19.


2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.


2005 ◽  
Vol 7 (2) ◽  
pp. 36-41 ◽  
Author(s):  
Herbert I. Karpatkin

Compared with other neurologic disorders, relatively little literature exists to define or support the role of exercise in MS. This review describes issues relating to exercise in patients with MS, discusses relevant literature, offers exercise guidelines for persons with MS, and suggests topics for future research. Unique aspects of MS that affect physical therapy are addressed, including disease progression, fatigue, and thermosensitivity. Review of the literature includes discussion of strength training, aerobic exercise, and respiratory training. While physical activity was once contraindicated in persons with MS, current literature supports its therapeutic benefits in these patients. More research could be focused on the specific types of exercise appropriate for this patient population.


2017 ◽  
Vol 312 (2) ◽  
pp. F266-F275 ◽  
Author(s):  
Michael S. Goligorsky

Three decades ago a revolutionary idea was born that ascribed to dysfunctional endothelia some manifestations of diabetes, the Steno hypothesis, so named after the Steno Diabetes Center, Gentofte, in Denmark. Here I briefly outline the accomplishments accrued in the past 15 years to buttress this hypothesis. Those include development of novel technological platforms to examine microcirculatory beds, deeper understanding of patterns of microvascular derangement in diabetes, pathophysiology of nitric oxide synthesis and availability, nitrosative and oxidative stress in diabetes, premature senescence of endothelial cells and the role of sirtuin 1 and lysosomal dysfunction in this process, and the state of endothelial glycocalyx and endothelial progenitor cells in diabetes. These pathophysiological findings may yield some therapeutic benefits.


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