Computational and experimental studies on the interaction between butyrylcholinesterase and fluoxetine: implications in health and disease

1. 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.

2. Here, our aim was to study the interaction between BChE and fluoxetine.

3. 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 V_m, K_m, k_cat and k_cat/K_m 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 K_i value of 36.3?±?4.7?µM.

4. Overall, both the low K_i 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.

     

Correction to: A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats

Metabolic Brain Disease -     

Genomic instability in fragile sites—still adding the pieces

Common fragile sites (CFSs) are specific genomic regions in normal chromosomes that exhibit genomic instability under DNA replication stress. As replication stress is an early feature of cancer development, CFSs are involved in the signature of genomic instability found in malignant tumors. The landscape of CFSs is tissue‐specific and differs under different replication stress inducers. Nevertheless, the features underlying CFS sensitivity to replication stress are shared. Here, we review the events generating replication stress and discuss the unique characteristics of CFS regions and the cellular responses aimed to stabilizing these regions.     

Case report: Evaluation of supernumerary teeth with computerized tomography

Radiographs play an important role in assessment of both the location and the typing of supernumerary teeth. In general, periapical, occlusal, and/or panoramic radiographs are sufficient for providing the information required by the clinician. These modalities, however, do not provide detailed information concerning the 3-dimensional relationship between supernumerary or ectopically impacted teeth and adjacent structures. This case report discusses the value of computerized tomography (CT) for evaluation of the root relationships of supernumerary teeth located palatally to maxillary permanent central incisors. CT accurately demonstrated the relationship between the supernumerary teeth and the permanent tooth roots.     

A method for positioning the premaxilla during impression making for a patient with bilateral cleft lip and palate: a clinical report

In patients with bilateral cleft lip and palate (BCLP), orthodontic and facial orthopedic treatments alone occasionally fail to resolve problems because of the absence of alveolar and palatal hard and soft tissue or contraction resulting from previous surgical repair. Prosthetic reconstruction of the anterior maxilla is important for these patients. Patients with BCLP have premaxillary displacement in up to 3 dimensions. It may be difficult to make impressions without deformation. This clinical report describes a method for positioning the mobile premaxilla during impression making for a patient with BCLP.     

The effect of platelet-rich plasma on osteochondral defects treated with mosaicplasty

Purpose

This study investigated the efficacy of platelet-rich plasma (PRP) on articular surfaces on which the mosaicplasty technique was performed. Our hypothesis was that PRP can accelerate the osseointegration process and enhance the quality of articular integrity after the mosaicplasty procedure.

Methods

Standard defects were created in the femoral groove of both patellofemoral joints of 12 New Zealand rabbits. PRP solution was placed inside the defect before fixation of the osteochondral autografts and injected inside the involved joint after capsular closure of the tested knees. The contralateral knees served as the control sides. The animals were euthanized three or six weeks after mosaicplasty, and both limbs were assessed according to Pineda’s histological grading scale. Significance level was set at p ≤ 0.05 a priori, and the Mann–Whitney U test was used for statistical analysis.

Results

Histologic findings at the interface between the transferred autograft and the original cartilage revealed better integration of the adjacent surfaces in the mosaicplasty with PRP group three weeks after the procedure; the difference was significant (p < 0.05). However, no significant difference in the transition zone was observed between the groups six weeks after the experiment (p = 0.59).

Conclusions

Our animal model showed that adjunctive use of PRP produced a better healing response and resulted in superior histological scores after three weeks compared with the mosaicplasty-only procedure. Interpretation of our results is important in terms of rapid return to previous activity levels. Thus, application of PRP can represent a valid therapeutic option for improving the efficacy of mosaicplasty by stimulating the local healing response.     

Retroanastomotic hernia after Moynihan's gastroenterostomy

Retroanastomotic hernias after gastroenterostomieseither antecolic or retrocolic-are extremely rare but are associated with high mortality rates due to delayed identification which precludes immediate surgical re-duction. In this report, we present a 77-year-old man with retroanastomotic herniation of the efferent loop segments that occurred 14 years after a Moynihan's gastroenterostomy.     

Malignant triton tumor of the gluteal region in a patient unaffected by neurofibromatosis: A case report

Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) made up of both malignant schwannoma cells and malignant rhabdomyoblasts.A 26-years-old male patient was admitted with an asymptomatic gluteal mass. Magnetic resonance imaging showed heterogeneous soft tissue mass and he underwent open biopsy. Malignant peripheral nerve sheath tumor was diagnosed. He was given adjuvant chemotherapy following the removal of the tumor with hip disarticulation. The tumor was diagnosed as “malignant triton tumor” based on pathological examination including immunohistochemical studies. There were no signs of metastasis but recurrence was observed at 9 months follow up.MTT is usually associated with Neurofibromatosis 1 and located in head, neck region. In this case sporadic involvement of gluteal region and aggressive behavior of the lesion despite radical surgery was demonstrated.     

Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma

International Urology and Nephrology - We aimed to assess an “Immunological Profile (IP)” including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects...