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المقدمة

الحمد لله رب العالمين الصلاة والسلام على سيدنا محمّد الأمين - صلى الله عليه وسلم- المبعوث رحمة للعالمين وعلى آله وأصحابه أجمعين ومن تبعهم بإحسان إلى يوم الدين.

 أما بعد:                    

فلا شكّ أنَّ البشرية، لم تعرف كتابًا حظي بالدرس، والتمحيص، واحتفاء الناس به، كما هو الحال مع (القرآن العظيم). فمنذ تنزل الوحي على قلب نبينا - صلّى الله عليه وسلّم - لم يتوقف تأثير هذا الكتاب على قـُلوب الناس، وعقولهم؛ وذلك لأنّه نزل مفصلاً، قيمًا، متصفـًا بمعجز النظم كما في قوله تعالى: ﴿لَا يَأْتِيهِ الْبَاطِلُ مِنْ بَيْنِ يَدَيهِ وَلَا مِنْ خَلْفِهِ تَنْزِيلٌ مِنْ حَكِيمٍ حَمِيدٍ﴾ (فصلت: 42). جعله الله متلوًا لا يمل على طول التلاوة، وعجيبًا لا تنقضي عجائبه.

وقد أنزل الله - عزّ وجلّ - القرآن الكريم بلسانٍ عربيّ مبين، وجعلهُ محكمًا فقال:﴿كِتَابٌ أُحْكِمَتْ آيَاتُهُ ثُمَّ فُصِّلَتْ مِنْ لَدُنْ حَكِيمٍ خَبِيرٍ﴾ (هود: 1). وجعله معجزًا؛ تحدى به العرب، أنْ يأتوا بمثله، أو بسورة من مثله فقال سبحانه وتعالى: ﴿فَأْتُوا بِسُورَةٍ مِنْ مِثْلِهِ وَادْعُوا شُهَداءَكُمْ مِنْ دُونِ اللَّهِ إِنْ كُنْتُمْ صَادِقِينَ﴾ (البقرة: 23). وحكم عليهم بالعجز أنْ يفعلوا ذلك في الماضي، أو الحاضر، أو المستقبل فقال: ﴿فَإِنْ لَمْ تَفْعَلُوا وَلَنْ تَفْعَلُوا فَاتَّقُوا النَّارَ الَّتِي وَقُودُهَا النَّاسُ وَالْحِجَارَةُ أُعِدَّتْ لِلْكَافِرِينَ﴾  [االبقرة: 24]. ولم يكن هذا التحدي للعرب الذين اشتهروا بالفصاحة وحدهم، بل كان للإنس والجنّ قاطبةً، يقول تعالى: ﴿قُلْ لَئِنِ اجْتَمَعَتِ الْإِنْسُ وَالْجِنُّ عَلَى أَنْ يَأْتُوا بِمِثْلِ هَذَا الْقُرْآنِ لَا يَأْتُونَ بِمِثْلِهِ وَلَوْ كَانَ بَعْضُهُمْ لِبَعْضٍ ظَهِيرًا﴾ [الإسراء: 88].

أما الفصاحة لهذه الايات الكريمة تنمي إلى أدب القرآن فالآداب لا تكون في الإنسان إلا شرائع، ولكن الإنسان إذا عَرِيَ من الأدب النفسي، فربما شرع لنفسه ما لا يصنع الشيطانُ أخبثَ منه بل ما يَركضُ فيه الشيطانُ ركضاً؛ وقلما انتفعَ مَن لا أدب له بشريعة من الشرائع وإن كانت في الغاية التي لا مذهبَ وراءها...

مستوى الالتزام التنظيمي لدى مُعلمي مدارس التعليم الأساسي بمحافظة البريمي في سلطنة عمان

هدفت الدراسة الحالية إلى التعرف على مستوى الالتزام التنظيمي لدى مُعلمي مدارس التعليم الأساسي بمحافظة البريمي في سلطنة عمان، واتبعت الدراسة المنهج الوصفي، كما استخدمت الاستبانة في جمع البيانات والمعلومات وتم تطبيقها على عينة مكونة من (369) معلماً ومعلمة. وتوصلت نتائج الدراسة إلى أن أن مستوى الالتزام التنظيمي لدى معلمي مدارس التعليم الأساسي بمحافظة البريمي في سلطنة عمان جاء عالياً بصورة إجمالية، كما جاء عالياً في جميع الأبعاد وهي: الالتزام المعياري، والعاطفي، والاستمراري، وأوضحت النتائج أيضاً عدم وجود فروق ذات دلالة إحصائية عند مستوى الدلالة (α ≤ 0.05 ) في استجابات عينة الدراسة من المعلمين لمستوى التزامهم بمدارس التعليم الأساسي بمحافظة البريمي في سلطنة عمان تُعزى لمتغيرات الجنس، والمؤهل العلمي، وسنوات الخبرة، والمسمى الوظيفي.

Binding Studies of Drug-Dna Complexes in the Absence and Presence of Ascorbic Acid Utilizing Electrochemical, Spectroscopic, Molecular Docking and Cell Culture Techniques

In the present work pharmacodynamic interactions of thirteen antineoplastic drugs with DNA were investigated using experimental cylic voltammetric and UV- Vis spectroscopic techniques and theoretical docking methods on molecular level. The experimental studies were carried out under physiological conditions i.e. pH 7.4, 4.7 and body temperature (309.5K). In the CV experiments interacting modes of antineoplstic drugs with DNA were determined on the basis of decrease in the peak current and shift in the peak position. It was observed that a positive shift in the peak position and gradual decrease in peak current was indicative of the intercalative behavior. Based on this observation all anthracycline based drugs i.e. doxorubicin, epirubicin, daunorubicin, mitoxantron, idarubicin, dactinomycin and nogalamycin were kept under the category of intercalators. Cisplatin, carboplatin, fluorouracil, etoposide, cyclophosphamide and bleomycin were considered to be non-intercalators due to abrupt decrease in peak current. In UV experiments interacting modes were determined from the variation in spectral absorbance and shift in spectral position. The most important parameter obtained from the experimental studies was the binding constant (K b ) which is an indicator of the binding strength of the drug with DNA. Molecular docking and QSAR studies were carried out for the prediction of interactions between antineoplastic drugs and double stranded DNA. Quantitative structure activity relationship was established using MOE software package showing good correlation of binding strength with various physicochemical parameters e.g. hydrophobic surface area (V surf ), E HOMO , E LUMO , partition coefficient (log P) and molar refractivity (M R ) of the drugs. Binding constants were also predicted from molecular docking studies and it was of the same order of magnitude as those obtained from the experimental techniques. Investigation of the interaction of three anthracyclines namely doxorubicin, epirubicin and daunorubicin with DNA in the presence and absence of two natural additives (ascorbic acid and nicotinc acid) under physiological conditions were carried out using above three techniques. From voltammetric data, binding constants, binding site sizes and Gibb’s free energy were calculated for the drug-DNA and drug- DNA-additive adducts. It was observed that the binding strength of drug-DNA iiicomplex generally increased in the presence of ascorbic acid and nicotinic acid. Molecular docking studies (using MOE) confirmed that in the presence of AA and NA number of hydrogen bonds and hydrophobic interactions are increased in the drug-DNA–additive adduct. It is a known fact that the drugs interact with DNA as well as with enzymes involved in DNA replication inside the cell. The presently studied thirteen antineoplasti drugs are the cytotoxic agents which inhibits the activity of DNA enzymes namely Topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In the studied work, we performed molecular docking studies of twelve antitumor drugs against these DNA enzymes in the absence and presence of ascorbic acid (AA). It was predicted that in most of the cases drug-enzyme interaction is enhanced in the presence of AA. The increase in the binding constant (K b ) of drug-enzyme complex in the presence of AA is a manifestation of this enhanced interaction. Quantitative structure activity relationship (QSAR) model for anticancer activity screening was also developed. These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity Pharmacodynamic drug interactions were also carried out on the cellular level using cell culture technique. Utilizing a multiwell plate cytotoxic assay, two non small cell carcinoma cell line (NSCLC) human carcinoma cell lines, H-1299 and H-157 were tested against eight antineoplastic agents alone and in combination with ascorbic acid (AA). In these cell lines, it was observed that a moderately cytotoxic concentration of AA (2mM) improved the cytotoxic activity of antitumor drugs. Dose dependent response curves were drawn to calculate the LD 50 values of the drugs for both cell lines. Percent cell inhibition of the drug in the presence of 2mM AA was determined in two combinations. In the first combination the concentration of the drug was taken equal to its LD 50 value whereas in the second combination it was 2mM. It was observed that combination effects between AA and drugs were partly synergistic and a consistent synergism was found between AA and all drugs for both cell lines. The only exception was that of bleomycin which exhibited an antagonistic effect with AA in H-157 cell line.
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