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.

     

The levels of plasma and salivary antioxidants in the patient with recurrent aphthous stomatitis

BACKGROUND: Despite plenty of research, the cause of recurrent aphthous stomatitis (RAS) remains obscure. It has been proposed that, the aetiological factors such as local trauma, smoking, vitamin deficiencies and viral infections lead to aphthae formation via final common pathway based on increased oxidative stress. The aim of this investigation was to evaluate the antioxidant enzyme superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) alterations in plasma and saliva, and in addition uric acid (UA) in saliva, in patients with RAS and healthy controls. METHODS: Thirty-two patients with RAS and 30 healthy controls were included into the study. The SOD, CAT, GSHPx and UA levels were measured in plasma and saliva in study and control groups. RESULTS: In the RAS group, although the mean SOD (P<0.001) and CAT (P<0.05) levels of plasma were lower, GSHPx (P<0.001) levels were higher than control group. The salivary concentrations of the SOD (P<0.001), CAT (P<0.05) and GSHPx (P<0.001) in RAS group were entirely opposite to plasma concentrations. UA were not significant between RAS group and controls. CONCLUSION: Since we found salivary SOD and CAT levels were high whereas plasma levels were low, it has been thought that, salivary defence mechanisms via antioxidant agents may be stimulated against to the ulcerous lesion. We consider that the organism might mobilize the antioxidant potential to the sites where they were needed. At this point, decrease of SOD and CAT levels in the plasma may be related to this shift. It is also thought that GSHPx secretion in the saliva may also be increased but the increase in its turnover may be responsible for the diminished activity.     

Rapidly advancing invasive endomyocardial aspergillosis.

The exposure to Aspergillus organisms/spores is likely common, but disease caused by tissue invasion with these fungi is uncommon and occurs primarily in the setting of immunosuppression. We report a case of rapidly advancing invasive endomyocardial aspergillosis secondary to prolonged usage of multiple broad-spectrum antibiotics in a nonimmunocompromised host. A 36-year-old cotton textile worker presented to our institution with a 3-month history of weight loss and fatigue. He reported receiving prolonged use of multiple broad-spectrum antibiotic treatment. The echocardiogram demonstrated multiple endomyocardial vegetations and a mass in the left atrium. Myocardial biopsy specimen revealed an invasive endomyocardial aspergillosis. The patient was investigated for immune deficiency including HIV, and this workup was negative. Treatment was started with amphotericin B and heparin for presumed left atrial thrombus. The patient died because of a rupture of mycotic aneurysm that resulted in cerebral hemorrhage. This case illustrates the risk of an invasive fungal infection in a nonimmunocompromised host who is a prolonged user of antibiotics in the setting of environmental exposure of opportunistic invasive fungal infections.     

Stereological evaluation of liver volume in living donor liver transplantation using MDCT via the Cavalieri method.

In living donor liver transplantation (LDLT), obtaining the precise volume of the graft is very important to decrease volume-related postoperative complications, especially in cases with suspected small-for size grafts. We used stereology based on the Cavalieri method (CM), a new method to measure liver graft volume, and compared the results with those obtained through intraoperative measurement (IOM) and through multidetector computed tomography (MDCT) measurement. Liver volumes estimated using the 3 methods were well-correlated with each other (r(2) = 0.94 and P < 0.001 for IOM and CM; r(2) = 0.91 and P < 0.001 for IOM and MDCT, and r(2) = 0.95 and P < 0.001 for CM and MDCT); however, they were different from each other (in descending order, 908 +/- 124 cm(2), 861 +/- 121 cm(2), and 777 +/- 168 cm(2) for MDCT, CM, and IOM, respectively). Although MDCT and CM overestimated the volumes, the results of CM were almost similar to those obtained via IOM. In conclusion, our results suggest that CM measured the liver graft volume more reliably. Thus, its use, particularly in cases with suspected small-for-size graft, may prove useful.     

Erectile dysfunction due to venous incompetence treated by dorsal vein ligation

The authors describe 14 cases of erectile dysfunction. The sites of leakage were detected by duplex or colour flow Doppler sonography. Treatment by dorsal vein ligation resulted in fairly good early responses, however, at 4-month follow-up the great majority of patients returned to the original functional state.     

Gallbladder sludge and acute pancreatitis induced by acute hepatitis A.

In this case report, a young woman with gallbladder sludge and acute pancreatitis due to acute hepatitis A (HAV) is presented. She was admitted to our hospital with abnormal hepatic enzymes. Five days prior to her admission, an initial abdominal ultrasound was performed at another hospital and revealed no abnormality, while her serum aspartate aminotransferase (AST) level was at the upper limit of normal (ULN) x 8. A second ultrasound was performed at our hospital and revealed a gallbladder wall thickness (9.3 mm), gallbladder sludge in the gallbladder lumen, pancreatic edema, ascites, and hepatomegaly while AST was at the ULN x 50. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness with coexisting sludge in the gallbladder lumen. HAV infection was diagnosed by the detection of immunoglobulin M against HAV in the serum. The patient underwent two repeated abdominal ultrasound examinations on the 5th (AST was at the ULN x 3) and the 20th days (AST was at the normal) after her discharge, and both revealed normal findings. In our case, we observed reversible changes in the hepatobiliary and pancreatic system which was related to the severity of hepatic necro-inflammation. HAV-associated pancreatitis may be due to the formation of biliary sludge during the acute phase of the viral illness, but this association needs further investigation.     

Synovial chondromatosis of four compartments of the knee: medial and lateral tibiofemoral spaces,patellofemoral joint and proximal tibiofibular joint

A case of synovial chondromatosis of the proximal tibiofibular joint in addition to lateral and medial tibiofemoral spaces and patellofemoral joint has been presented.