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ABSTRACT: This study describes the interaction between human acetylcholinesterase (AChE), a key regulator of central and peripheral cholinergic function, and the widely used nitrogen mustard alkylating agent, cyclophosphamide (CP). Modeling of the AChE sequence (NCBI Accession No: AAI05061.1) was performed using 'Swiss Model Workspace'. The protein-model was submitted to the Protein Model Database and was assigned accession number PM0077393. A plot showing normalized QMEAN scores versus protein size was made to compare the model with a non-redundant set of Protein Data Bank structures, which gave a Z-score QMEAN as -0.58. The predicted local error for the modeled structure was found to be well within tolerable limits. Z-score values for Cβ interaction, all atom interaction, solvation and torsion were found to be -1.10, -0.90, -0.06 and -0.40, respectively. Docking between CP and AChE was performed using 'Autodock4.2'. Apart from other interaction-types, six carbon atoms of CP (C1, C2, C3, C4, C6 and C7) were determined to be involved in hydrophobic interactions with amino acid residues Y121, W233, L323, F331, F335 and Y338 of the 'acyl pocket' within AChE. Five carbon atoms of CP (C2, C4, C5, C6 and C7) were involved in hydrophobic interactions with 3 amino acid residues within the enzyme's 'catalytic site'. In conclusion, hydrophobic interactions play a major role in the appropriate positioning of CP within the 'acyl pocket' as well as 'catalytic site' of AChE to permit suitable orientation and allow docking. This information may aid the design of more potent and versatile AChE-inhibitors as pharmacologic tools and drugs to characterize and treat neurological disorders, and additionally provides a model whose value can be quantitatively assessed by X-ray crystallographic analysis of the AChECP three-dimensional structure.
CNS & neurological disorders drug targets 10/2011; 10(7):845-8. · 3.57 Impact Factor
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ABSTRACT: The main aims of this study were, first, to estimate the need for periodontal care among adult residents of Saudi Arabia using the community periodontal index of treatment need (CPITN) and, second, to quantify the relationship between the frequency of using the 'Miswak' and the need for periodontal care. The Miswak is a stick made from the roots of the Arak tree (Salvadora persica) and is used for oral hygiene purposes by many cultures. A total sample of 480 adults aged 35 to 44 years and 65 years and older from the cities of Mecca and Jeddah was included in the study. The findings indicate that the level of need for periodontal care in the sample chosen is low when compared with the findings of similar studies undertaken in other countries. The frequent use of the 'Miswak' was associated with a lower need for treatment.
Community dental health 01/1992; 8(4):323-8. · 0.75 Impact Factor
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ABSTRACT: We have applied a multi-stage computer algorithm for normalization of distributions and calculation of reference intervals of some urine characteristics and constituents. The study analyzed 24-h urines, collected from adult male Saudis from different socioeconomic classes, for volume, pH, osmolality, specific gravity, creatine, creatinine, urea and uric acid. Frequency distributions, for each analyte, were found to be nongaussian as judged by the coefficients of skewness and kurtosis, chi 2 and Kolmogorov-Smirnov tests, and from probability plots. Data were transformed to gaussian distributions by multistage log-power transformation. Stepwise, this procedure removed skewness and residual kurtosis. Using the gaussian transformed data the reference intervals were estimated parametrically as the mean +/- 2 SD. In addition, the non-parametric percentile technique was applied to estimate these values. The former intervals were found to have narrower 0.90 confidence limits than the latter. When established limits were compared with those reported for Western subjects urine volume and uric acid showed the most marked variation.
Clinica Chimica Acta 07/1987; 166(1):9-16. · 2.54 Impact Factor
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Clinica Chimica Acta 12/1986; 160(3):319-26. · 2.54 Impact Factor
