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 preventive role of wheat germ oil against sertraline‐induced testicular damage in male albino rats

Sertraline is an antidepressant medication used extensively in the therapy of depression. The present investigation was intended to estimate the actual protective role of wheat germ oil on sertraline‐caused testicular injury in albino rats. Sertraline (human therapeutic dose, 15.63 mg/kg) was orally administrated to rats for 28 successive days. Sertraline‐administered rats were concurrently supplemented with wheat germ oil (human therapeutic dose, 68.75 mg/kg) for 28 successive days. Sertraline administration induced an elevation in testicular DNA damage and acute testicular damage illustrated by the histopathological alterations including marked degeneration and necrosis of germ cells lining seminiferous tubules, as well as interstitial oedema, congestion of interstitial blood vessel. Wheat germ oil administration potentially mitigated the histopathological alterations of sertraline‐administered rats. Lipid peroxidation, oxidative stress biomarker, showed a significant elevation in testicular tissue of sertraline‐administered rats. Furthermore, glutathione content and catalase activity were decreased in testicular tissue of sertraline‐administered rats. Serum testosterone level was elevated in sertraline‐administered rats. Wheat germ oil significantly reduced lipid peroxidation of testicular tissue and improved the antioxidant defences. Finally, wheat germ oil has a preventive role against testicular damage induced by sertraline in rats probably via its potential to prevent reactive oxygen species.     

The effect of topical parasympathomimetics on corneal epithelial healing in rabbits

Corneal wound healing is an important process that involves interaction between the different corneal cell layers, growth factors, and environmental conditions. More powerful therapies for the treatment of delayed epithelial wound healing are still being proposed. The objective of this study is to investigate the effects of the direct-acting parasympathomimetic agents on the healing process of corneal epithelium in rabbits. The corneal epithelial defects, 10 mm in diameter, were created in 32 eyes of 16 island rabbits by combination of chemical debridement using n-heptanol and mechanical scraping. Animals were randomly divided into four groups. Groups 1, 2 and 3 were treatment groups; each group consisted of four rabbits (8 eyes). The animals in these groups were treated with topical 1% acetylcholine (ACh), 2% pilocarpine, and 0.75% carbachol drops respectively. In group 4, four rabbits (8 eyes) were used as control group and left for spontaneous healing. The length and area of the defect were measured at days 3,6,9,12,15,18 and 22 after wounding. Areas of the photographically documented fluorescein-stained defects were measured by planimetry. All eyes in the treatment groups reepithelialized completely. The duration for reepithelialization in Groups 1 and 2 was 12 days, and 18 days for Group 3. In the control group reepithelialization occurred within 22 days. The healing rates of corneal epithelium were statistically significantly faster in all treatment groups as compared with the control group at all times (p=0.0001 to 0.0279). Although the rates of wound healing varied, all of the parasympathomimetics used in the present study were found to facilitate wound healing. Our results indicate that direct-acting cholinergic agents, especially ACh and pilocarpine, may have an important therapeutic role in the treatment of severe corneal epithelial injury.     

Peripheral seventh nerve palsy due to transorbital intracranial penetrating pontine injury

The case of a child injured by a knitting needle penetrating transorbitally and intracranially, resulting in carotid cavernous fistula and pontine injury, is reported. After receiving medical and endovascular treatment, the only remaining abnormal neurological manifestation was right peripheral facial nerve palsy. The clinical sequences of events and the demonstration of a pontine lesion leading to peripheral facial palsy are presented. Facial nuclear injury with a penetrating trauma is an extremely rare condition. It is important to identify the anatomical regions injured in penetrating traumas. The lesions must be identified by computerized tomography, magnetic resonance imaging, clinical and laboratory investigation.     

Correlation between Karnofsky Performance Status Scale and Short-Form Health Survey in patients on maintenance hemodialysis

BACKGROUND: Assessment of quality of life is vital inmonitoring response to various treatment measures. Various instruments, which include both generic and disease-specific instruments, are used in the assessment of health-related quality of life (HRQOL). In this study, we compare two commonly used generic instruments. OBJECTIVES: The objective of this study was to compare two generic instruments, the Karnofsky Performance Status Scale and the SF-36 Health Survey in hemodialysis (HD) patients. The study also aims to find out the association (if any) between HRQOL scores using these two scales and various clinical and biochemical parameters. MATERIALS AND METHODS: Sixty-two maintenance HD patients were recruited after informed consents were obtained. Detailed sociodemographic data was obtained. They were assessed during their regular HD sessions. Serum chemistry (which included serum urea, creatinine, Na+, K+, HCO3-, Ca2+, Po4(2-)), albumin, globulin, total protein and hemoglobin (g/dl) were assessed in all the patients. Adequacy of HD was assessed using second-generation Daugirdais formula. HRQOL was assessed using the Karnofsky and SSF-36 instruments and the scores collated and compared. Data was analyzed using SPSS version 10. RESULTS: Fifty-five patients completed the study (27 males and 28 females, mean age 40.76 +/- 11.05 years and age range of 20-65 years). There was a significant positive correlation between Karnofsky scores and all eight SF-36 domains, but only physical functioning, social functioning and role limitation due to emotional problems maintained the significance on multiple regression analysis. The serum creatinine and hemoglobin postively correlated with physical function, bodily pain, social functioning and Karnofsky scores. Age of the patients correlated negatively with two SF-36 dimensions (physical functioning and role limitation due to physical fitness) and Karnofsky scores. CONCLUSION: This study revealed a good correlation between Karnofsky performance status scale and the short-form (SF36) health survey in this Egyptian population. Age, serum creatinine and hemoglobin significantly influence quality of life in this HD patient population.     

The Hawaii family study of cognition: A reply

Differences in age and number of children tested per family between two ethnic groups (Americans of Japanese ancestry and Americans of European ancestry) have a trivial effect on differences in regressions of midchild on midparent for tests of specific cognitive abilities. Although the regression of offspring on midparent value is not a mathematical function of the spouse correlation, an empirical association between these two measures of familial resemblance is expected for characters with nonzero heritability. Such an association is reported for anthropometric characters. Since age effects contribute to the covariance of family members, age correction of family cognitive data is essential.The results reported here are made possible by collaboration of a group of investigators (G. C. Ashton, R. C. Johnson, M. P. Mi, and M. N. Rashad at the University of Hawaii, and J. C. DeFries, G. E. McClearn, S. G. Vandenberg, and J. R. Wilson at the University of Colorado) supported by NSF Grant GB-34720 and Grant HD-06669 from the National Institute of Child Health and Human Development.     

Laser in situ keratomileusis for myopic anisometropia in children.

PURPOSE: To evaluate the visual and refractive results of laser in situ keratomileusis (LASIK) in pediatric patients with myopic anisometropia and amblyopia, and to assess the predictability, safety, and efficacy of the procedure in children. METHODS: Fourteen patients aged 7 to 12 years with myopic anisometropia and amblyopia had LASIK in the more myopic eye (14 eyes) using the Chiron Automatic Corneal Shaper and the Chiron-Technolas Keracor 116 excimer laser. Preoperative spherical equivalent manifest refraction ranged from -4.62 to -12.50 D (mean, -7.87 D) and spectacle-corrected visual acuity ranged from 20/40 to 20/100 (median, 20/50). All patients completed a minimum follow-up of 12 months. RESULTS: One year after LASIK, spherical equivalent manifest refraction ranged from 0 to -1.50 D (mean, -0.55 D). Spectacle-corrected visual acuity improved in all eyes (range, 20/20 to 20/40; median, 20/25). Six eyes (42.9%) had a postoperative spectacle-corrected visual acuity of 20/20. Uncorrected visual acuity was 20/40 or better in 10 eyes (71.4%) (range, 20/20 to 20/70; median, 20/30). Uncorrected visual acuity exceeded preoperative spectacle-corrected visual acuity in all eyes by an average of 2 lines. There were no significant complications. CONCLUSION: LASIK was effective for correction of myopic anisometropia in this small group of children and reversed refractive amblyopia. LASIK in these children was safe, predictable, and provided good visual results.