Amyotrophic lateral sclerosis (ALS) affects motor neurons in the cerebral cortex, brainstem and spinal cord and leads to death due to respiratory failure within three to five years. Although the ...clinical symptoms of this disease were first described in 1869 and it is the most common motor neuron disease and the most common neurodegenerative disease in middle-aged individuals, the exact etiopathogenesis of ALS remains unclear and it remains incurable. However, free oxygen radicals (i.e., molecules containing one or more free electrons) are known to contribute to the pathogenesis of this disease as they very readily bind intracellular structures, leading to functional impairment. Antioxidant enzymes, which are often metalloenzymes, inactivate free oxygen radicals by converting them into a less harmful substance. One of the most important antioxidant enzymes is Cu
Zn
superoxide dismutase (SOD1), which is mutated in 20% of cases of the familial form of ALS (fALS) and up to 7% of sporadic ALS (sALS) cases. In addition, the proper functioning of catalase and glutathione peroxidase (GPx) is essential for antioxidant protection. In this review article, we focus on the mechanisms through which these enzymes are involved in the antioxidant response to oxidative stress and thus the pathogenesis of ALS and their potential as therapeutic targets.
This study presents the development and validation of a novel capillary zone electrophoresis method for the precise determination of glatiramer acetate and its amino acid constituents. A 120 mmol dm
...−3
phosphoric acid solution adjusted to pH 1.9 with Tris, supplemented with 20 mmol dm
−3
triethylamine to achieve a final of pH 2.1, resulted in a repeatable analysis of glatiramer acetate. The method demonstrated a limit of detection and quantification of 39.2 µg cm
−3
and 130.7 µg cm
−3
, respectively. This method allows for the rapid control of glatiramer acetate-based pharmaceuticals and distinguishes glatiramer acetate from the amino acids used in its synthesis.
Graphical abstract
Present demographic changes demonstrate that the number of elderly people is growing at a frenetic pace. This shift in population consequently results in many social and economic problems, which ...burden the social and economic systems of countries. The aging process is associated with age-related diseases, the most common of which are dementia and Alzheimer's disease, whose main symptom is a decline in cognitive function, especially memory loss. Unfortunately, it cannot be cured. Therefore, alternative approaches, which are cost-effective, safe, and easy to implement, are being sought in order to delay and prevent cognitive impairment. The purpose of this review was to explore the effect of multidomain lifestyle intervention strategies on the delay and/or prevention of cognitive impairment in healthy older individuals. The methods are based on a literature review of available sources found on the research topic in three acknowledged databases: Web of Science, Scopus, and PubMed. The results of the identified original studies reveal that multidomain lifestyle interventions generate significant effects. In addition, these interventions seem feasible, cost-effective, and engaging. Thus, there is a call for the implementation of effective lifestyle prevention programs, which would involve goal-setting and would focus on the prevention of crucial risk factors threatening the target group of elderly people, who are at risk of cognitive decline and dementia.
Smart mobile phone use is increasing worldwide, as is the ability of mobile devices to monitor daily routines, behaviors, and even cognitive changes. There is a growing opportunity for users to share ...the data collected with their medical providers which may serve as an accessible cognitive impairment screening tool. Data logged or tracked in an app and analyzed with machine learning (ML) could identify subtle cognitive changes and lead to more timely diagnoses on an individual and population level. This review comments on existing evidence of mobile device applications designed to passively and/or actively collect data on cognition relevant for early detection and diagnosis of Alzheimer's disease (AD). The PubMed database was searched to identify existing literature on apps related to dementia and cognitive health data collection. The initial search deadline was December 1, 2022. Additional literature published in 2023 was accounted for with a follow-up search prior to publication. Criteria for inclusion was limited to articles in English which referenced data collection via mobile app from adults 50+ concerned, at risk of, or diagnosed with AD dementia. We identified relevant literature (
= 25) which fit our criteria. Many publications were excluded because they focused on apps which fail to collect data and simply provide users with cognitive health information. We found that although data collecting cognition-related apps have existed for years, the use of these apps as screening tools remains underdeveloped; however, it may serve as proof of concept and feasibility as there is much supporting evidence on their predictive utility. Concerns about the validity of mobile apps for cognitive screening and privacy issues remain prevalent. Mobile applications and use of ML is widely considered a financially and socially viable method of compiling symptomatic data but currently this large potential dataset, screening tool, and research resource is still largely untapped.
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ...ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.
Current demographic trends indicate that the population is aging. The aging process is inevitably connected with cognitive decline, which manifests itself in worsening working memory, processing ...speed, and attention. Therefore, apart from pharmacological therapies, non-pharmacological approaches which can influence cognitive performance (such as physical activities or healthy diet), are being investigated. The purpose of this study is to explore the types of nutritional interventions and their benefits in the prevention and delay of cognitive delay in healthy older individuals. The methods used in this study include a literature review of the available studies on the research topic found in Web of Science, Scopus, and MEDLINE. The findings show that nutritional intervention has a positive impact on cognitive function in healthy older people. However, it seems that the interactions between more than one nutrient are most effective. The results reveal that specifically the Mediterranean diet appears to be effective in this respect. Moreover, the findings also indicate that multi-domain interventions including diet, exercise, cognitive training, and vascular risk monitoring have a far more significant effect on the enhancement of cognitive functions among healthy older individuals.
We aimed was to assess the factors influencing therapy choice and clinical outcome after 3-4 months in patients with cerebral venous sinus thrombosis (CVST). In a retrospective, bi-centric study, the ...set consisted of 82 consecutive CVST patients (61 females; mean age 33.5 ± 15.7 years). Following data were collected: baseline characteristics, presence of gender-specific risk factors (GSRF), location and extent of venous sinus impairment, clinical presentation, type of treatment, recanalization, presence of parenchymal lesions, and clinical outcome after 3-4 months (assessed using the modified Rankin Scale mRS, with excellent outcome defined as mRS 0-1). Multivariate logistic regression analysis was used for statistical evaluation. After 3-4 months, complete recovery was achieved in 41 (50%) and excellent clinical outcome in 67 (81.7%) patients. Female sex (OR 0.11; p = 0.0189) and presence of focal neurologic deficit (OR 0.16; p = 0.0165) were identified as significant independent negative predictors and, the presence of GSRF (OR 15.63; p = 0.0011) as significant independent positive predictor of excellent clinical outcome. In conclusion, in our CVST patients, the presence of GSRF was associated with excellent clinical outcome, while the female sex itself was associated with poorer clinical outcome.
Summary Background Pain is a common non-motor symptom of Parkinson's disease. We investigated the analgesic efficacy of prolonged-release oxycodone–naloxone (OXN PR) in patients with Parkinson's ...disease and chronic, severe pain. Methods We did this phase 2 study in 47 secondary care centres in the Czech Republic, Germany, Hungary, Poland, Romania, Spain, and the UK. We enrolled patients with Hoehn and Yahr Stage II–IV Parkinson's disease, at least one type of severe pain, and an average 24-h pain score of at least 6 (assessed on an 11-point rating scale from 0=no pain to 10=pain as bad as you can imagine). Participants were randomly assigned (1:1) with a validated automated system (block size four) to either oral OXN PR or placebo for 16 weeks (starting dose oxycodone 5 mg, naloxone 2·5 mg, twice daily). Patients and investigators were masked to treatment assignment. The primary endpoint was average 24-h pain score at 16 weeks in the full analysis population. This study is registered with EudraCT (2011-002901-31) and ClinicalTrials.gov ( NCT01439100 ). Findings We enrolled 202 patients; 93 were assigned to OXN PR and 109 to placebo; the full analysis population consisted of 88 patients versus 106 patients. Least squares mean average 24-h pain score at 16 weeks in the full analysis population was 5·0 (95% CI 4·5 to 5·5) in the OXN PR group versus 5·6 (5·1 to 6·0) in the placebo group (difference −0·6, 95% CI −1·3 to 0·0; p=0·058). Similar proportions of patients in each group had adverse events (60/92 65% vs 76/109 70%), treatment-related adverse events (52/92 57% vs 62/109 57%), and serious adverse events (5/92 5% vs 7/109 6%). Treatment-related nausea was more common in the OXN PR group than in the placebo group (16/92 17% vs 10/109 9%), as was treatment-related constipation (16/92 17% vs 6/109 6%). Interpretation The primary endpoint, based on the full analysis population at week 16, was not significant. Nonetheless, the results of this study highlight the potential efficacy of OXN PR for patients with Parkinson's disease-related pain and might warrant further research on OXN PR in this setting. Funding Mundipharma Research.
Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on ...doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals' whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales-hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.
Background:The composition of intra-arterial clots might influence the efficacy of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute occlusions within large cerebral arteries. The ...aims were to assess the factors associated with blood clot structure and the impact of thromboembolus structure on MT using stent-retrievers in patients with acute large artery IS in the anterior circulation.Methods and Results:In an observational cohort study, we studied the components of intra-arterial clots retrieved from large cerebral arteries in 80 patients with acute IS treated with MT with or without i.v. thrombolysis (IVT). Histology of the clots was carried out without knowledge of the clinical findings, including the treatment methods. The components of the clots, their age, origin and semi-quantitative graded changes in the architecture of the fibrin components (e.g., “thinning”) were compared via neuro-interventional, clinical and laboratory data. The most prominent changes in the architecture of the fibrin components in the thromboemboli were associated with IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21–10.10, P=0.02) and platelet count (OR, 2.94; 95% CI: 1.06–8.12, P=0.04).Conclusions:In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.
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