This study investigated the effects of local injection of cerium oxide nanoparticles (CeONPs) in a rat spinal cord injury (SCI) model. Thirty-six adult male Wistar rats were divided into 4 groups: controls (healthy animals), sham (laminectomy), SCI (laminectomy+SCI induction), and treatment (laminectomy+SCI induction+intrathecal injection of CeONPs immediately after injury). SCI was induced using an aneurysm clip at the T12-T13 vertebral region. Motor performance and pain threshold tests were performed weekly; H&E staining and measurement of cavity sizes were performed 6 weeks after injury. The expression of granulocyte colony-stimulating factor (GCSF), P44/42 MAPK, P-P44/42 MAPK, Tau, myelin-associated glycoprotein(MAG) was evaluated after 6 weeks by Western blot. The Basso, Beattie, and Bresnahan locomotor scoring scales improved in animals receiving CeONPs compared with SCI animals. The cavity sizes were less in the treatment group. GCSF expression was similar in the animals receiving CeONPs compared with the SCI group but the expression of ERK1/ERK2 and phospho-ERK was lower than in the SCI group. Expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group. These data indicate that the use of CeONPs may improve motor functional recovery in SCI.
Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO2) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthesized, and a gelatin solution containing cerium oxide nanoparticles was attached to the scaffold. For the animal study, 40 male Wistar rats were randomly divided into 4 groups (n = 10): (a) Control; (b) Spinal cord injury (SCI); (c) Scaffold (SCI + scaffold without CeO2 nanoparticles); (d) Scaffold-CeO2 (SCI + scaffold containing CeO2 nanoparticles). After creation of a hemisection SCI, scaffolds were placed at the site of injury in groups c and d, and after 7 weeks the rats were subjected to behavioral tests and then sacrificed for preparation of the spinal cord tissue to measure the expression of G-CSF, Tau and Mag proteins by Western blotting and Iba-1 protein by immunohistochemistry. The result of behavioral tests confirmed motor improvement and pain reduction in the Scaffold-CeO2 group compared to the SCI group. Decreased expression of Iba-1 and higher expression of Tau and Mag in the Scaffold-CeO2 group compared to the SCI group could be the result of nerve regeneration caused by the scaffold containing CeONPs as well as relief of pain symptoms.
Graphical Abstract
Background
Today, gabapentinoids such as Gabapentin (GBP) and pregabalin (PGB) are widely used as painkillers. This may alter the function of the nervous system; hence their results may include a difference in memory and processes that end in memory formation. This study aims to conclude whether gabapentinoids can alter memory or not by reviewing and analyzing clinical and preclinical studies.
Material and methods
A comprehensive search was carried out in databases including PUBMED, EMBASE, SCOPUS, and Web of Science. In the included studies, memory was measured as an outcome variable in clinical or preclinical studies.
Result
A total of 21 articles (4 clinical, 17 preclinical) were included in the meta-analysis by STATA Software. The results showed that memory changes under the influence of GBP. Both the administrated dosage and the time of administration are important in the final results and latency time of retention. GBP administration in healthy animals increased latency time, whereas if the administration of GBP took place exactly before training, the latency time increased slightly.
Short-term administration of PGB in healthy volunteers is accompanied by transient side effects on the CNS. However, the number and homogeneity of the studies were not such that a meta-analysis could be performed on them.
Conclusion
Clinical and preclinical studies showed that PGB administration did not confirm its improving memory effect. GBP administration in healthy animals increased latency time and improved memory. Although it depended on the time of administration.
Spinal cord injury (SCI) is a destructive disease usually induced by high-energy trauma. Patients with SCI suffer from paralysis, sensory and locomotor dysfunction, urinary incontinence or gastrointestinal disorder [1] . The SCI-related impairment leads to vast personal complaint and significant costs to society [2,3] . The global incidence of acute SCI is calculated as almost 10 cases per 100,000 people, resulting in over 700,000 new cases annually detected worldwide [4] . The pathophysiology of SCI has two different phases. Primary injuries cause hemorrhage, the disorder of cell membrane integrity, and neurotransmitter and ion inequality that directly affect neural loss. Secondary injuries include the advanced inflammatory, and ischemic and apoptotic cascade following the initial injury [2] .Following SCI, neuropathic pain, as a chronic pain presents at the same or below the level of damage [1] . This type of pain is known as
Background
Remdesivir is being studied and used to treat coronavirus disease 2019 (COVID-19). This study aimed to systematically identify, critically evaluate, and summarize the findings of the studies on the cost-effectiveness of remdesivir in the treatment of hospitalized patients with COVID-19.
Methods
In this systematic review, PubMed, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched for studies published between 2019 and 2022. We included all full economic evaluations of remdesivir for the treatment of hospitalized patients with COVID-19. Data were summarized in a structured and narrative manner.
Results
Out of 616 articles obtained in this literature search, 12 studies were included in the final analysis. The mean score of the Quality of Health Economic Studies (QHES) for the studies was 87.66 (high quality). All studies were conducted in high-income countries (eight studies in the USA and one study in England), except for three studies from middle-to-high-income countries (China, South Africa, and Turkey). Six studies conducted their economic analysis in terms of a health system perspective; five studies conducted their economic analysis from a payer perspective; three studies from the perspective of a health care provider. The results of five studies showed that remdesivir was cost-effective compared to standard treatment. Furthermore, the therapeutic strategy of combining remdesivir with baricitinib was cost-effective compared to remdesivir alone.
Conclusions
Based on the results of the present study, remdesivir appears to be cost-effective in comparison with the standard of care in China, Turkey, and South Africa. Studies conducted in the United States show conflicting results, and combining remdesivir with baricitinib is cost-effective compared with remdesivir alone. However, the cost-effectiveness of remdesivir in low-income countries remains unknown. Thus, more studies in different countries are required to determine the cost-effectiveness of this drug.
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