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In plasma, 94.3% of total radioactivity was aprocitentan. In urine and feces, 5 and 2, respectively (in feces one being aprocitentan) main products were identified. Metabolism data of aprocitentan identified two main elimination pathways, glucosidation to M3 and hydrolysis to M1, representing approximately 25% and 32% of the radioactive dose, respectively.
Based on these metabolism data, aprocitentan can be concomitantly administered without dose adjustment with drugs that are inhibitors or inducers of any metabolizing enzyme, specifically cytochrome P450 enzymes.
Based on these metabolism data, aprocitentan can be concomitantly administered without dose adjustment with drugs that are inhibitors or inducers of any metabolizing enzyme, specifically cytochrome P450 enzymes.
Curcumin is a well-documented bioactive compound present in Curcuma sp., a tropical medicinal plant. This substance exhibits broad spectrum biological activities including antivirus. Despite, the lack of pharmaceutical properties of curcumin limits its clinical use.
This study aims to produce curcumin nanoemulsion with different surface charge (curcumin (+) nanoemulsion and curcumin (-) nanoemulsion) and to evaluate its physical characteristics, in vitro cell cytotoxicity and antiviral activity against dengue virus (DENV) 1 and 2.
Two forms of nanoemulsion were prepared which were differed from their surface charge through spontaneous procedure resulting similar characteristics except the zeta potential value. Cytotoxicity was determined using RT-PCR method in A549 cell line and anti-DENV properties were determined by calculation of inhibitory concentration 50 (IC50) value.
The positively charge of curcumin-loaded nanoemulsion showed better effect in reducing the viral replication represented by lower IC50 value. In addition, DENV-1 was more sensitive and responsive to curcumin as compared to DENV-2.
Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin suggesting a promising approach for alternative treatment for dengue virus infection.
Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin suggesting a promising approach for alternative treatment for dengue virus infection.
Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts.
The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera.
This was retrospective study, conducted snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment.
141 cases were investigated including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1years. Age group 30-39 years accounted for highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from the rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and sever in 1patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%).
Snakebite is one of the significantlife-threatening environmental events.Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.
Snakebite is one of the significantlife-threatening environmental events.Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.
Heat shock protein90 (Hsp90) is overexpressed in tumor cells, thus the inhibition of the Hsp90 ATPase activity would be a meaningfully an effective strategy in cancer therapy.
The present work was aimed at four steps designing new Hsp90 inhibitors as anti-cancer by a virtual screening study; synthesize designed compounds; biological evaluation of them and finally molecular dynamic (MD) simulations of best compounds.
A virtual screening study was performed on a library (100 compounds) of the ZINC database with benzimidazole scaffold; then an extracted compound and two derivatives were synthesized. The anti-proliferative and ATPase inhibitory activities of these compounds were evaluated by MTT and ATPase inhibition assays, respectively. The western blot analysis was performed to the evaluation of the expression level of Hsp70 and Her2 proteins. Finally, 200 ns molecular dynamic simulation was carried out to confirm stability the strongest synthesized compound in Hsp90 active site.
ZINC00173501 compound with an aminobenzimidazole scaffold was chosen by the virtual screening study. ZINC00173501 compound and two of its derivatives were synthesized. ATPase inhibitory activity of three synthesized compounds shown that ZINC00173501 compound was the most potent inhibitor (IC50= 8.6 μM) with the anti-proliferative activity 14.41 μM, 19.07 μM and more than 100 μM against MCF-7, HeLa and HUVEC cell lines, respectively. ABT-199 price The high level of Hsp70 expression and low level of Her2 expression confirmed ZINC00173501 as an Hsp90 inhibitor. Finally, molecular dynamics simulation showed that ZINC00173501 was stable in Hsp90 active cite during 200 ns simulation.
The biological evaluation results show that 2-aminobenzimidazole scaffold could be suggested as a lead for inhibition of Hsp90.
The biological evaluation results show that 2-aminobenzimidazole scaffold could be suggested as a lead for inhibition of Hsp90.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via angiotensin-converting enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to the human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population.
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