scholarly journals Translational control of antibiotic resistance

Open Biology ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 190051 ◽  
Author(s):  
Anne Witzky ◽  
Rodney Tollerson ◽  
Michael Ibba

Many antibiotics available in the clinic today directly inhibit bacterial translation. Despite the past success of such drugs, their efficacy is diminishing with the spread of antibiotic resistance. Through the use of ribosomal modifications, ribosomal protection proteins, translation elongation factors and mistranslation, many pathogens are able to establish resistance to common therapeutics. However, current efforts in drug discovery are focused on overcoming these obstacles through the modification or discovery of new treatment options. Here, we provide an overview for common mechanisms of resistance to translation-targeting drugs and summarize several important breakthroughs in recent drug development.

2009 ◽  
Vol 21 (S2) ◽  
pp. 27-34 ◽  
Author(s):  
Sven G. Meuth ◽  
Stefan Bittner ◽  
Heinz Wiendl

Abstract:Multiple sclerosis (MS) is regarded as a prototypic inflammatory autoimmune central nervous system disorder causing neurological disability in young adults. Recommended basic immunomodulatory therapies of MS are currently interferon beta and glatiramer acetate. Both have proven to be clinically and paraclinically effective and clinical evidence suggests that treatment should be initiated as early as possible.However, despite the fact that therapeutic options for MS have significantly been widened over the past decade there is still tremendous activity in the search for new treatment options for MS.One important development in the field is reflected by the substantial number of promising results for oral therapies. Various phase III clinical trials are currently being initiated or are already underway evaluating the efficacy of a variety of orally administered agents, including cladribine, teriflunomide, laquinimod, fingolimod and fumaric acid. It is hoped that these oral therapies for MS further broaden our armament for MS therapy.


Perfusion ◽  
2003 ◽  
Vol 18 (4) ◽  
pp. 253-256 ◽  
Author(s):  
Joseph J Sistino

Treatment for cardiovascular disease has dramatically changed the surgical patient population over the past 10 years. Advances in medical management and interventional cardiovascular procedures have delayed surgery in many adults, and the surgical pool has begun to decrease despite an aging population. This affects perfusionists in terms of new psychological and technical challenges, and has serious consequences and implications for the future of the profession. This study will review the changing patterns of diagnosis and treatment of cardiovascular disease in the USA over the past 10 years by examining the annual surgical procedure rates and correlating them with the number of practicing perfusionists and new student graduates. The purpose of this review is to project the future employment opportunities for perfusionists. The second part of the paper will look at the alternative roles perfusionists have expanded into as a result of changes in the treatment of cardiovascular disease. The results of an e-mail survey of perfusionists will be presented to identify new applications of perfusion technology.


Author(s):  
W. Curt LaFrance ◽  
Laura H. Goldstein

Psychogenic nonepileptic seizures (PNES) have been in the medical literature for centuries. However, treatments were limited, being based on uncontrolled data, until the past decade. Treatment advances published since 2010 have included pilot controlled trials using psychotherapies, psychoeducational approaches, medications, and combined pharmacological and psychotherapeutic approaches that provide new treatment options for patients with PNES. This chapter describes these controlled trials in detail. It also covers studies of treatments for other functional neurological disorders including PNES. One conclusion from this review is that future studies still need to improve on as-yet limited sample sizes and provide insights into predictors of treatment outcome so that rational decisions can be made about which treatments offer the best outcome and who is likely to best respond to which treatment.


2010 ◽  
Vol 74 (3) ◽  
pp. 417-433 ◽  
Author(s):  
Julian Davies ◽  
Dorothy Davies

SUMMARY Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4842-4842
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
John Crowley ◽  
Herbert Duvivier ◽  
Youram Nassir ◽  
...  

Abstract New treatment options have greatly improved the overall survival for MM pts. Although many baseline prognostic factors have been identified among pts with MM in the past, few studies have evaluated prognostic factors during the past five years when these new treatment options became available. Included in the newer regimens for myeloma pts is the use of monthly infusions of ZOL to reduce skeletal complications for MM pts. During this time of changes in the therapy for MM pts, complications associated with administration of bisphosphonates have been reported among MM pts. The outcome for patients with these complications has not been well-defined. The goal of this study was to identify baseline and on-treatment prognostic factors for determining overall survival of MM pts treated with ZOL. The inclusion criteria for this study included a diagnosis of MM and having received at least one dose of ZOL in our clinic. One hundred consecutive pts were analyzed in this retrospective study. The median survival of this group was 117 months. Risk factors for an earlier death included occurrence of a SRE (hazard ratio [HR] = 3.06), increased serum creatinine (HR = 3.35), elevated serum calcium (HR = 2.60), and ISS Stage II or III at diagnosis (HR = 2.04). Notably, diabetes was found to be a significant risk factor for SREs but not overall survival (P = 0.022). Ten pts developed ONJ, of whom nine are alive and one died in remission (non-MM-related). The 2-year incidence of ONJ was approximately 5%. There was a trend toward increased risk of ONJ for diabetes, smoking, and alcohol use. When evaluating the course of ONJ, only one pt showed progression, while six improved or resolved, and three remained stable. All but one pt with ONJ remain on monthly ZOL therapy. In regards to the disease status of the nine pts surviving with ONJ, five are in complete remission, two with ongoing partial responses, and two have stable disease. The skeletal morbidity rate (SMR) was only 0.16 SRE/year among all 100 pts analyzed. Notably, pts with ONJ had a lower SMR (0.07 SRE/year) than the 90 pts treated with ZOL who did not develop ONJ (0.18 SRE/year). Importantly, overall survival was superior among pts with ONJ versus pts without ONJ in this study when analyzed both by a landmark analysis and in a time-dependent fashion. Thus, development of new SREs, elevated serum creatinine, increased serum calcium and ISS Stage II or III at diagnosis predicted for an earlier death. With active monitoring for ONJ and early input from dental experts, ONJ has been mild to moderate in severity, had minimal impact on overall quality of life, and improved or healed in the majority of pts. In this study, absence of SREs (time-dependent) and occurrence of ONJ were associated with an improved overall survival (P ≤ .01 for each). These results suggest that with proper management, ONJ is a manageable, infrequent complication of ZOL that may be associated with a reduced SRE risk and improved overall survival. This study also suggests the avoidance of SREs is associated with an increased life expectancy; and, thus, reduction in these events through ongoing bisphosphonate therapy is important in the overall management of MM pts.


1998 ◽  
Vol 9 (4) ◽  
pp. 522-540 ◽  
Author(s):  
M.C. Roberts

In the last 20 years, changes in world technology have occurred which have allowed for the rapid transport of people, food, and goods. Unfortunately, antibiotic residues and antibiotic-resistant bacteria have been transported as well. Over the past 20 years, the rise in antibiotic-resistant gene carriage in virtually every species of bacteria, not just oral/respiratory bacteria, has been documented. In this review, the main mechanisms of resistance to the important antibiotics used for treatment of disease caused by oral/respiratory bacteria-including β-lactams, tetracycline, and metronidazole-are discussed in detail. Mechanisms of resistance for macrolides, lincosamides, streptogramins, trimethoprim, sulfonamides, aminoglycosides, and chloramphenicol are also discussed, along with the possible role that mercury resistance may play in the bacterial ecology.


Author(s):  
Paul K. Paik ◽  
Rathi Narayana Pillai ◽  
Christopher S. Lathan ◽  
Sylvia A. Velasco ◽  
Vassiliki Papadimitrakopoulou

The past few years have witnessed a rapid shift in the treatments for patients with squamous cell lung cancers (SQCLCs) after the U.S. Food and Drug Administration approval of a number of immune checkpoint inhibitors as second-line therapies for patients with non–small cell lung cancers. These series of approvals marked the first substantial improvement in overall survival for patients with SQCLC in over a decade. Further gains have been made more recently with the incorporation of immune checkpoint inhibition in the first-line setting, either as monotherapy or in combination with chemotherapy. These advances have, however, exposed existing deficiencies in the management of this disease. Despite a deeper understanding of the genomic alterations that characterize SQCLCs and years of trial work targeting these alterations, personalized therapies remain out of hand. Future studies will continue to focus on identifying targeted approaches to expand the treatment options for our patients.


2002 ◽  
Vol 111 (12) ◽  
pp. 1066-1075 ◽  
Author(s):  
Chantal M. Giguère ◽  
Nancy M. Bauman ◽  
Richard J. H. Smith

Lymphangiomas are congenital malformations of the lymphatic system. These lesions occur most often in the head and neck area, and their treatment continues to be a challenge. Fortunately, a number of advances have occurred in the diagnosis and management of lymphatic malformations in the past decade. The purpose of this article is to clarify the embryology, pathogenesis, histopathology, and classification of these lesions, as well as to describe their various forms of clinical presentation. We provide a complete review of the diagnostic measures available and thoroughly discuss new therapeutic interventions proposed to treat lymphangiomas.


2015 ◽  
Vol 8 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Pablo Ruiz Sada ◽  
Hannah Cohen ◽  
David Isenberg

Advances in our knowledge of the pathogenic mechanisms of antiphospholipid syndrome have been achieved in the past few years. Apart from the well-known role of anti-β2-glycoprotein I antibodies, complement, endocrine and genetic factors and a variety of other molecules are now under investigation. These new approaches should lead to novel explanations and potential new treatment options.


2019 ◽  
Vol 25 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Marjorie C. Argollo ◽  
Mariangela Allocca ◽  
Federica Furfaro ◽  
Laurent Peyrin-Biroulet ◽  
Silvio Danese

Over the past decades, the advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD. However, primarily and more importantly, secondary loss of response to anti-TNF agents, is often observed. Thus, new treatment options have been actively explored and some have already been incorporated in the current clinical practice. Among the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have been first presented, in clinical practice, by the anti-p40 mAb ustekinumab in Crohn’s disease (CD). More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.


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