RESUMO
Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.
RESUMO
During the early stages of the COVID-19 pandemic, infection rates were high and symptoms were severe. Medical resources, including healthcare experts and hospital facilities, were put to the test to ensure their readiness to deal with this unique event. An intensive care unit (ICU) is expected to be required by many hospitalized patients. Many hospitals worldwide lacked resources during the pandemic's peak stages, particularly in critical care treatment. Because of this, there were issues with capacity, as well as an excessive influx of patients. Additionally, even though the research location provides medical care to a sizable population, there is a paucity of scientific data detailing the situation as it pertains to COVID-19 patients during the height of the outbreak. Therefore, this study aimed to identify and describe the features of COVID-19 patients hospitalized in the ICU of one of the multispecialty hospitals in Riyadh, Saudi Arabia. An observational retrospective study was conducted using a chart review of COVID-19 patients admitted to the ICU between March 2020 and December 2020. To characterize the patients, descriptive statistics were utilized. An exploratory multivariate regression analysis was carried out on the study cohort to investigate the factors that were shown to be predictors of death and intubation. Only 333 (29.33%) of the 1135 samples from the hospital's medical records were used for the final analysis and interpretation. More than 76% of the patients in the study were male, with a mean BMI of 22.07 and an average age of around 49 years. The most frequent chronic condition found among the patients who participated in the study was diabetes (39.34%), followed by hypertension (31.53%). At the time of admission, 63 of the total 333 patients needed to have intubation performed. In total, 22 of the 333 patients died while undergoing therapy. People with both diabetes and hypertension had a 7.85-fold higher risk of death, whereas those with only diabetes or hypertension had a 5.43-fold and 4.21-fold higher risk of death, respectively. At admission, intubation was necessary for many male patients (49 out of 63). Most intubated patients had hypertension, diabetes, or both conditions. Only 13 of the 63 patients who had been intubated died, with the vast majority being extubated. Diabetes and hypertension were significant contributors to the severity of illness experienced by COVID-19 participants. The presence of multiple comorbidities had the highest risk for intubation and mortality among ICU-admitted patients. Although more intubated patients died, the fatality rate was lower than in other countries due to enhanced healthcare management at the ICU of the study center. However, large-scale trials are needed to determine how effective various strategies were in preventing ICU admission, intubation, and death rates.