Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.
Here, our aim was to study the interaction between BChE and fluoxetine.
Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.
Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.
We review the spectrum of cutaneous disorders associated with inflammatory and neoplastic plasmacytic pathology. Because plasma cells are derived from B‐lymphocytes our overview includes discussion of certain lymphoplasmacytic proliferations. It is structured along histopathological lines, addressing conditions characterized by (a) cutaneous plasma cell infiltrates, (b) deposits of plasma cell products or their derivatives in the skin and (c) miscellaneous, poorly understood cutaneous complications of plasmacytic disorders. Lesions arising primarily in the skin and those due to cutaneous involvement by multisystem disorders are addressed. The range includes a spectrum of tumefactive and circulatory manifestations. We highlight key clinical and pathological features of the different conditions and outline recent advances in our understanding of these entities. By emphasizing the dermatopathological characteristics of this spectrum of disorders we hope to hone the diagnostic accuracy of practitioners in the field. 相似文献
Introduction: It is now clear that circulating cell-free ribonucleic acids (ccfRNAs), including messenger RNA (mRNA) and miRNA, are potential cancer biomarkers. As ccfmiRNA is relatively more stable than ccfmRNA, research should concentrate on developing novel methods to preserve the stability of ccfmRNA and standardization of the protocol which includes extraction, detection, and multicenter validation.
Areas covered: This literature review concentrates on the potential of ccfRNA being used as a biomarker in cancer, with special focus on mRNAs and microRNAs (miRNAs).
Expert opinion: With the advancement of high-throughput technologies such as RNA sequencing, a panel of biomarkers will be used for the diagnosis, prognosis and therapeutic monitoring of cancer patients. In order to achieve this important target, bioinformatics education to pathologists, scientists, and technologists in molecular diagnostic laboratories is essential. Moreover, the panel of these new ccfRNAs biomarkers has to obtain approval or clearance from an authority such as the US Food and Drug Administration (FDA), and the standard of utilizing these new protocols has to be recognized via accreditation exercise. Therefore, there is still a long way to go before an extensively use of ccfRNA biomarkers in cancer patients can be realized. 相似文献
Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans. 相似文献
BackgroundComputerized tomography‐guided celiac plexus neurolysis has become almost a safe technique to alleviate abdominal malignancy pain. We compared the single needle technique with changing patients’ position and the double needle technique using posterior anterocrural approach.MethodsIn Double Needles Celiac Neurolysis Group (n = 17), we used two needles posterior anterocrural technique injecting 12.5 mL phenol 10% on each side in prone position. In Single Needle Celiac Neurolysis Group (n = 17), we used single needle posterior anterocrural approach. 25 mL of phenol 10% was injected from left side while patients were in left lateral position then turned to right side. The monitoring parameters were failure block rate and duration of patient positioning, technique time, Visual Analog Scale, complications (hypotension, diarrhea, vomiting, hemorrhage, neurological damage and infection) and rescue analgesia.ResultsThe failure block rate and duration of patient positioning significantly increased in double needles celiac neurolysis vs. single needle celiac neurolysis (30.8% vs. 0.13.8±1.2 vs. 8.9 ± 1; p = 0.046, p ≤ 0.001 respectively). Also, the technique time increased significantly in double needles celiac neurolysis than single needle celiac neurolysis (24.5 ± 5.1 vs. 15.4 ± 1.8; p ≤ 0.001). No significant differences existed as regards visual analogue scale: double needles celiac neurolysis = 2 (0‐5), 2 (0‐4), 3 (0‐6), 3 (2‐6) and single needle celiac neurolysis = 3 (0‐5), 2 (0‐5), 2 (0‐4), 4 (2‐6) after 1 day, 1 week, 1 and 3 months respectively. However, visual analogue scale in each group reduced significantly compared with basal values (p ≤ 0.001). There were no statistically significant differences as regards rescue analgesia and complications (p > 0.05).ConclusionSingle needle celiac neurolysis with changing patients’ position has less failure block rate, less procedure time, shorter duration of patient positioning than double needles celiac neurolysis in abdominal malignancy. 相似文献