scholarly journals Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1270
Author(s):  
Mònica Millán ◽  
Núria DeGregorio-Rocasolano ◽  
Natàlia Pérez de la Ossa ◽  
Sílvia Reverté ◽  
Joan Costa ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Optimal Dose ◽  
Iron Chelator ◽  
Good Clinical Outcome ◽  
Dose Selection ◽  
Iron Saturation ◽  
Deferoxamine Mesylate ◽  
The Impact ◽  
New Evidence

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40–60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40–60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50–58% of the 40–60 mg/Kg/day DFO-treated patients.

New Empirical Evidence of the Role of Interest Groups in Influencing the Growth of Government

2000 ◽  
Vol 18 (2) ◽  
pp. 83-100
Author(s):  
Gary A. Wagner ◽  
Russell S. Sobel
Keyword(s):  
Interest Groups ◽  
Political Action ◽  
Political Action Committees ◽  
The Public ◽  
The Status ◽  
Short Run ◽  
Using Data ◽  
The Impact ◽  
New Evidence

Abstract We provide new evidence regarding the role of interest groups in influencing the size and growth of government spending. Using data on the change in individual legislators’ total voted and sponsored spending from the status quo, we explore this relationship in a manner closer to the public choice tradition. Examining the impact diat interest groups have on individual legislators’ preferences for new spending, we find that interest groups within a legislator’s district exhibit more influence on the short-run growth of the budget than do Political Action Committees.

scholarly journals Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 89 ◽  
Author(s):  
Rosita Stanzione ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
Maurizio Forte ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Epigenetic Modifications ◽  
Review Article ◽  
Epigenetic Changes ◽  
Therapeutic Approaches ◽  
Nutritional Factors ◽  
New Therapeutic Approaches ◽  
Different Types ◽  
The Impact

Epigenetics is the branch of molecular biology that studies modifications able to change gene expression without altering the DNA sequence. Epigenetic modulations include DNA methylation, histone modifications, and noncoding RNAs. These gene modifications are heritable and modifiable and can be triggered by lifestyle and nutritional factors. In recent years, epigenetic changes have been associated with the pathogenesis of several diseases such as diabetes, obesity, renal pathology, and different types of cancer. They have also been related with the pathogenesis of cardiovascular diseases including ischemic stroke. Importantly, since epigenetic modifications are reversible processes they could assist with the development of new therapeutic approaches for the treatment of human diseases. In the present review article, we aim to collect the most recent evidence concerning the impact of epigenetic modifications on the pathogenesis of ischemic stroke in both animal models and humans.

scholarly journals The Role of Gut Microbiota in an Ischemic Stroke

2021 ◽  
Vol 22 (2) ◽  
pp. 915
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Ischemic Stroke ◽  
Intestinal Microflora ◽  
Intestinal Bacteria ◽  
Intestinal Microbiome ◽  
Gut Dysfunction ◽  
Development And Aging ◽  
Host Metabolism ◽  
The Impact ◽  
The Brain

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke.

The impact of the reputation of underwriter and sponsoring representative on IPO underwriting fees

2016 ◽  
Vol 6 (4) ◽  
pp. 342-366 ◽  
Author(s):  
Chao Chen ◽  
Xinrong Wang
Keyword(s):  
Initial Public Offering ◽  
Political Connection ◽  
Content Type ◽  
Underwriting Fees ◽  
The One ◽  
Public Offering ◽  
The Impact ◽  
New Evidence ◽  
Practical Implications

Purpose The purpose of this paper is to analyze the effect of the reputation of underwriters and sponsoring representatives on initial public offering (IPO) underwriting fees, and further investigates the role of ownership and political connection. Design/methodology/approach The methodology includes three models. Model 1 empirically investigates the effect of underwriter’s reputation on underwriting fee. Model 2 studies the effect of sponsoring representative’s reputation on underwriting fee. Model 3 further examines the effect of underwriter’s reputation and sponsoring representative reputation on the underwriting fee controlling for the impact of ultimate controlling ownership and political connection. Findings The study documents that underwriters’ and sponsoring representatives’ reputation can result in reputational premiums. In the IPO of state-owned enterprises (SOEs), the reputation of underwriters and sponsoring representatives does not significantly affect the underwriting fees. In the IPO of non-state-owned enterprises (NSOEs), there is a significantly positive correlation between underwriters’ and sponsoring representatives’ reputation and underwriting fees. Further research results show that, on the one hand, the effect of underwriters’ and sponsoring representatives’ reputation on underwriting fees is not significant in the IPO of NSOEs with political connection. On the other hand, underwriting fees are positively associated with underwriters’ and sponsoring representatives’ reputation in the IPO of NSOEs without political connection. Research limitations/implications The sponsoring representative’s fee is not disclosed separately, which makes it difficult to distinguish the incremental effect from underwriter’s services and reputation. Practical implications NSOEs relative to SOEs are more likely to pay higher underwriting fees for hiring underwriter and sponsoring representative with better reputation during the process of IPO. Social implications The reputation of underwriter and sponsoring representative does not matter to SOEs but does matter to NSOEs. However, NSOEs’ political connection affects underwriter fees. Originality/value This paper provides new evidence of sponsoring representatives’ reputation and political connection on the underwriting fees in the IPO in Chinese SOEs and NSOEs.

Persistent Inequality? Trade, Factor Endowments, and Inequality in Republican Latin America

2013 ◽  
Vol 73 (1) ◽  
pp. 38-78 ◽  
Author(s):  
Leticia Arroyo Abad
Keyword(s):  
Nineteenth Century ◽  
Latin America ◽  
Theoretical Framework ◽  
Data Set ◽  
Factor Endowments ◽  
The Impact ◽  
New Evidence ◽  
Persistent Inequality

Using a new data set, this article presents new evidence on inequality in Latin America for the nineteenth century and studies the effects of factor endowments and trade on inequality. Recent research has highlighted the link between the colonial origins of inequality and its persistence in Latin America. We find that inequality varied substantially throughout the century and across the region. We identify the impact of changing factor endowments and trade on inequality using a simple theoretical framework. This work suggests that the role of initial colonial origins has been overemphasized as important changes took place during postcolonial times.

Possible role of glucocorticoids in a complement-activated state induced by cobra venom factor in rats

1986 ◽  
Vol 112 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Kiwao Nakano ◽  
Seiji Suzuki ◽  
Oh Chanho ◽  
Kazuo Yamashita
Keyword(s):  
Complement Activation ◽  
Serum Levels ◽  
Iron Chelator ◽  
Cobra Venom ◽  
Cyclooxygenase Inhibitors ◽  
Cobra Venom Factor ◽  
Deferoxamine Mesylate ◽  
Thromboxane Synthetase ◽  
Activated State

Abstract. Activation of the complement system of adrenalectomized rats with an injection of cobra venom factor (CVF) caused death of the rats within 2.5 h. Morphologically, this activation provoked distinct congestion of the gastric glandular mucosa and pulmonary leukostasis. Pretreatment of the animals with dexamethasone abolished the undesirable responses completely. Injection of CVF to intact rats produced only slight responses, but caused a marked increase in the serum levels of corticosterone. Dexamethasone was found to be replaced by promethazine (H1-antihistamine) or dimethylsulphoxide (scavenger of hydroxyl radicals) but not by indomethacine, ibuprofen (cyclooxygenase inhibitors), deferoxamine mesylate (iron chelator) or imidazole (thromboxane synthetase inhibitor). These results suggest that glucocorticoids protect the animals from the adverse effects of excessive complement activation and that they act as an inhibitor of the production or action of histamine and toxic oxygen products induced by complement activation.

scholarly journals Polyphenols and Ischemic Stroke: Insight into One of the Best Strategies for Prevention and Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1967
Author(s):  
Francesca Pacifici ◽  
Valentina Rovella ◽  
Donatella Pastore ◽  
Alfonso Bellia ◽  
Pasquale Abete ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Causes Of Death ◽  
Epidemiological Studies ◽  
Brain Protection ◽  
Functional Therapy ◽  
Beneficial Effects ◽  
Long Time ◽  
The Impact ◽  
Insight Into

Ischemic stroke (IS) is still among the leading causes of death and disability worldwide. The pathogenic mechanisms beyond its development are several and are complex and this is the main reason why a functional therapy is still missed. The beneficial effects of natural compounds against cardiovascular diseases and IS have been investigated for a long time. In this article, we reviewed the association between the most studied polyphenols and stroke protection in terms of prevention, effect on acute phase, and rehabilitation. We described experimental and epidemiological studies reporting the role of flavonols, phenolic acid, and stilbens on ischemic mechanisms leading to stroke. We analyzed the principal animal models used to evaluate the impact of these micronutrients to cerebral blood flow and to molecular pathways involved in oxidative stress and inflammation modulation, such as sirtuins. We reported the most significant clinical trials demonstrated as the persistent use of polyphenols is clinically relevant in terms of the reduction of vascular risk factors for IS, such as Atrial Fibrillation. Interestingly, different kinds of polyphenols provide brain protection by activating different pathways and mechanisms, like inducing antithrombotic effect, such as Honokiol. For this reason, we discussed an appropriate integrative use of them as a possible therapeutic alternative against stroke.

Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients

2015 ◽  
Vol 40 (3-4) ◽  
pp. 130-136 ◽  
Author(s):  
Zhaolu Wang ◽  
Adrian Wong ◽  
Wenyan Liu ◽  
Jie Yang ◽  
Winnie C.W. Chu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Transient Ischemic Attack ◽  
Cerebral Microbleeds ◽  
Cognitive Domains ◽  
Deep Region ◽  
Ischemic Attack ◽  
The Impact

Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

scholarly journals The Impact of Sex on Arterial Ischemic Stroke in Young Patients: From Stroke Occurrence to Poststroke Consequences

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 238
Author(s):  
Beata Sarecka-Hujar ◽  
Ilona Kopyta
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Young Patients ◽  
Protective Role ◽  
Arterial Ischemic Stroke ◽  
Clinical Presentations ◽  
Children And Young Adults ◽  
The Subject ◽  
The Impact

The male sex has been suggested to predominate in paediatric patients with arterial ischemic stroke (AIS), especially in newborns. The explanation for this phenomenon remains unsatisfactory since it focuses on the analysis of the potential relationship with trauma and arterial dissection. In turn, in some populations of young adults, men suffer from AIS more frequently than women, which may be related to the protective role of oestrogen. On the other hand, certain data indicate that women dominate over men. Some of the disparities in the frequencies of particular symptoms of AIS and poststroke consequences in both children and young adults have been suggested; however, data are scarce. Unfortunately, the low number of studies on the subject does not allow certain conclusions to be drawn. For adults, more data are available for patients aged over 60 years, the results of which are more obvious. The present literature review aimed to discuss available data on the prevalence of AIS, its clinical presentations, and poststroke consequences in regard to the sex of young patients. We considered young patients to be children from birth up to the age of 19 years of life and young adults to be individuals up to the age of 55 years. The role of sex hormones in AIS and possible gender differences in genetic risk factors for AIS were also discussed briefly.

scholarly journals Cross-Border Mobility Responses to Covid-19 in Europe: New Evidence from Facebook Data

2021 ◽  
Author(s):  
Frederic Docquier ◽  
Nicolas Golenvaux ◽  
Siegfried Nijssen ◽  
Pierre Schaus ◽  
Felix Stips
Keyword(s):  
Predictive Power ◽  
International Travel ◽  
School Closures ◽  
Commuting Flows ◽  
Cross Border ◽  
Containment Measures ◽  
Modelling Techniques ◽  
The Impact ◽  
New Evidence

Abstract BackgroundWe use a unique database on Facebook users’ mobility to study the daily evolution of cross-border movements of people during the Covid-19 pandemic. To limit censoring issues, we focus on 45 pairs of European countries, and document the changes in daily traffic during an entire pandemic year. We rely on regression and machine learning models to identify the role of infection threats and containment policies. Permutation techniques allow us to compare the impact and predictive power of these two categories of variables. ResultsIn contrast with studies on within-border mobility, our models point to a stronger importance of containment policies in explaining changes in cross-border traffic as compared with international travel bans and fears of being infected. The latter are proxied by the numbers of Covid-19 cases and deaths at destination. Although the ranking among coercive policies varies across modelling techniques, containment measures in the destination country (such as cancelling of events, restrictions on internal movements and public gatherings), and school closures in the origin country (influencing parental leaves) have the strongest impacts on cross-border movements. ConclusionWhile descriptive in nature, our findings have policy-relevant implications. Cross-border movements of people predominantly consist of labor commuting flows and business travels. These economic and essential flows are marginally influenced by the fear of infection and international travel bans. They are mostly governed by the stringency of internal containment policies and the ability to travel.

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