scholarly journals AB5 Enterotoxin-Mediated Pathogenesis: Perspectives Gleaned from Shiga Toxins

Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 62
Author(s):  
Erika N. Biernbaum ◽  
Indira T. Kudva

Foodborne diseases affect an estimated 600 million people worldwide annually, with the majority of these illnesses caused by Norovirus, Vibrio, Listeria, Campylobacter, Salmonella, and Escherichia coli. To elicit infections in humans, bacterial pathogens express a combination of virulence factors and toxins. AB5 toxins are an example of such toxins that can cause various clinical manifestations, including dehydration, diarrhea, kidney damage, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Treatment of most bacterial foodborne illnesses consists of fluid replacement and antibiotics. However, antibiotics are not recommended for infections caused by Shiga toxin-producing E. coli (STEC) because of the increased risk of HUS development, although there are conflicting views and results in this regard. Lack of effective treatment strategies for STEC infections pose a public health threat during outbreaks; therefore, the debate on antibiotic use for STEC infections could be further explored, along with investigations into antibiotic alternatives. The overall goal of this review is to provide a succinct summary on the mechanisms of action and the pathogenesis of AB5 and related toxins, as expressed by bacterial foodborne pathogens, with a primary focus on Shiga toxins (Stx). The role of Stx in human STEC disease, detection methodologies, and available treatment options are also briefly discussed.

2019 ◽  
Vol 21 (10) ◽  
pp. 734-748 ◽  
Author(s):  
Baoling Guo ◽  
Qiuxiang Zheng

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.


Thrombosis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Jonathan S. Bleeker ◽  
William J. Hogan

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jan Philipp Delling ◽  
Tobias M. Boeckers

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition, which is characterized by clinical heterogeneity and high heritability. Core symptoms of ASD include deficits in social communication and interaction, as well as restricted, repetitive patterns of behavior, interests, or activities. Many genes have been identified that are associated with an increased risk for ASD. Proteins encoded by these ASD risk genes are often involved in processes related to fetal brain development, chromatin modification and regulation of gene expression in general, as well as the structural and functional integrity of synapses. Genes of the SH3 and multiple ankyrin repeat domains (SHANK) family encode crucial scaffolding proteins (SHANK1-3) of excitatory synapses and other macromolecular complexes. SHANK gene mutations are highly associated with ASD and more specifically the Phelan-McDermid syndrome (PMDS), which is caused by heterozygous 22q13.3-deletion resulting in SHANK3-haploinsufficiency, or by SHANK3 missense variants. SHANK3 deficiency and potential treatment options have been extensively studied in animal models, especially in mice, but also in rats and non-human primates. However, few of the proposed therapeutic strategies have translated into clinical practice yet. Main text This review summarizes the literature concerning SHANK3-deficient animal models. In particular, the structural, behavioral, and neurological abnormalities are described and compared, providing a broad and comprehensive overview. Additionally, the underlying pathophysiologies and possible treatments that have been investigated in these models are discussed and evaluated with respect to their effect on ASD- or PMDS-associated phenotypes. Conclusions Animal models of SHANK3 deficiency generated by various genetic strategies, which determine the composition of the residual SHANK3-isoforms and affected cell types, show phenotypes resembling ASD and PMDS. The phenotypic heterogeneity across multiple models and studies resembles the variation of clinical severity in human ASD and PMDS patients. Multiple therapeutic strategies have been proposed and tested in animal models, which might lead to translational implications for human patients with ASD and/or PMDS. Future studies should explore the effects of new therapeutic approaches that target genetic haploinsufficiency, like CRISPR-mediated activation of promotors.


2009 ◽  
Vol 03 (01) ◽  
pp. 41 ◽  
Author(s):  
Götz Ulrich Grigoleit ◽  
Markus Kapp ◽  
Hermann Einsele ◽  
◽  
◽  
...  

Primary cytomegalovirus (CMV) infection often presents as an asymptomatic self-limiting disease in immunocompetent individuals and is followed by latent persistence in different host tissues. However, solid organ transplant (SOT) recipients and patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of life-threatening complications caused by CMV infection. Direct effects (or CMV disease) are marked by viral proliferation in a variety of tissues and organs. Clinical manifestations that are observed after SOT and alloHSCT are gastroenteritis, pneumonitis, hepatitis, uveitis, retinitis, encephalitis and graft rejection. In contrast to the direct effects, indirect effects are a consequence of the maintenance of persistent low-level viral replication and have been associated with an increased risk of rejection and graft dysfunction, graft-versus-host disease, accelerated atherosclerosis, opportunistic infections, malignancies, posttransplant diabetes and Guillain-Barré syndrome. This article aims to summarise these indirect effects of CMV, their possible causes and possible treatment strategies.


Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Amelie Schramm ◽  
Nikolaus De Gregorio ◽  
Peter Widschwendter ◽  
Visnja Fink ◽  
Jens Huober

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.


2003 ◽  
Vol 15 (5) ◽  
pp. 1-7 ◽  
Author(s):  
James K. Liu ◽  
Douglas L. Brockmeyer ◽  
Andrew T. Dailey ◽  
Meic H. Schmidt

Object Aneurysmal bone cysts of the spine are benign, highly vascular osseous lesions of unknown origin that may present difficult diagnostic and therapeutic challenges. They are expansile lesions containing thin-walled, blood-filled cystic cavities that cause bone destruction and sometimes spinal deformity and neurological compromise. The treatment of aneurysmal bone cysts of the spine remains controversial according to the literature. In this review, the authors discuss the clinical manifestations, pathophysiological features, neuroimaging characteristics, and treatment strategies for these lesions. Methods Treatment options include simple curettage with bone grafting, complete excision, embolization, and radiation therapy. Reconstruction and stabilization of the spine may be warranted if deformity and instability are present. Special factors need to be considered in the management of these lesions. Conclusions Complete excision of aneurysmal bone cysts offers the best chance of cure and spinal decompression if neurological deficits are present.


2013 ◽  
Vol 6 (1) ◽  
pp. 14-19
Author(s):  
Mary Virmani1 ◽  
Luis Ortega ◽  
Loay Salman ◽  
Tushar Vachharajani ◽  
Arif Asif ◽  
...  

Takayasu’s arteritis is a rare disorder characterized by granulomatous and necro-inflammatory disease of the aorta and its major branches. Its etiology remains unknown. We report a young woman with Takayasu’s arteritis affecting the aortic arch, carotid, mesenteric, celiac and bilateral renal arteries resulting in severe hypertension, unilateral renal atrophy and renal insufficiency. The immunosuppressive therapy did not halt the progression of her vascular disease, which required revascularization procedures on numerous occasions. Here, the clinical manifestations and histopathological features of Takayasu’s arteritis are reviewed. In addition, the available medical treatment options including glucocorticoids, cytotoxic agents and TNF-alpha inhibitors are discussed. Furthermore, current revascularization procedures such as percutaneous transluminal angioplasty and reconstructive vascular surgery in the treatment of occlusive vasculopathy due to Takayasu’s arteritis are discussed. Although the prognosis of this debilitating disease has improved over the past two decades, a better understanding of its etiology and pathogenesis will facilitate the discovery of effective target-specific treatment strategies with a narrow adverse effects profile.


2018 ◽  
Vol 22 (4) ◽  
pp. 18-39
Author(s):  
Timothy H.J. Goodship ◽  
H. Terence Cook ◽  
Fadi Fakhouri ◽  
Fernando C. Fervenza ◽  
Veronique Fremeaux-Bacchi ◽  
...  

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015  Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of  these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and  assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians  who are caring for such patients, recommendations for best  treatment strategies were discussed at length, providing the  evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda  was proposed to resolve outstanding controversial issues. 


2004 ◽  
Vol 17 (4) ◽  
pp. 926-941 ◽  
Author(s):  
Saul Tzipori ◽  
Abhineet Sheoran ◽  
Donna Akiyoshi ◽  
Arthur Donohue-Rolfe ◽  
Howard Trachtman

SUMMARY Hemolytic uremic syndrome (HUS) is a disease that can lead to acute renal failure and often to other serious sequelae, including death. The majority of cases are attributed to infections with Escherichia coli, serotype O157:H7 strains in particular, which cause bloody diarrhea and liberate one or two toxins known as Shiga toxins 1 and 2. These toxins are thought to directly be responsible for the manifestations of HUS. Currently, supportive nonspecific treatment is the only available option for the management of individuals presenting with HUS. The benefit of antimicrobial therapy remains uncertain because of several reports which claim that such intervention can in fact exacerbate the syndrome. There have been only a few specific therapies directed against neutralizing the activities of these toxins, but none so far has been shown to be effective. This article reviews the literature on the mechanism of action of these toxins and the clinical manifestations and current management and treatment of HUS. The major focus of the article, however, is the development and rationale for using neutralizing human antibodies to combat this toxin-induced disease. Several groups are currently pursuing this approach with either humanized, chimeric, or human antitoxin antibodies produced in transgenic mice. They are at different phases of development, ranging from preclinical evaluation to human clinical trials. The information available from preclinical studies indicates that neutralizing specific antibodies directed against the A subunit of the toxin can be highly protective. Such antibodies, even when administered well after exposure to bacterial infection and onset of diarrhea, can prevent the occurrence of systemic complications.


2020 ◽  
Vol 244 (3) ◽  
pp. 501-510 ◽  
Author(s):  
H Y Li ◽  
Y X Liu ◽  
L Harvey ◽  
S Shafaeizadeh ◽  
E M van der Beek ◽  
...  

The prevalence of gestational diabetes mellitus (GDM) is estimated at 14% globally, and in some countries, such as Singapore, exceeds 20%. Both women and children exposed to GDM have an increased risk of later metabolic diseases, cardiovascular disease and other health issues. Beyond lifestyle changes and pharmaceutical intervention using existing type 2 diabetes medications for expecting women, there are limited treatment options for women with GDM; targeting better outcomes of potentially affected infants is unexplored. Numerous animal models have been generated for understanding of pathological processes of GDM development and for development of treatment strategies. These models, however, suffer from limited windows of opportunity to examine risk factors and potential intervention options. By combining short-term high-fat diet (HFD) feeding and low-dose streptozotocin (STZ) treatments before pregnancy, we have established a mouse model with marked transient gestation-specific hyperglycemia, which allows testing of nutritional and pharmacological interventions before, during and beyond pregnancy.


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