Design and synthesis of New Methyl4-Hydroxy-1-Alkyl-2-aryl 5-Oxo 2,5-Dihydropyrrole-3-Carboxylate Derivatives as Selective COX-2 Inhibitors

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly medications in the world. The mechanism of action of these drugs is the inhibition of cyclooxygenase (COX) enzyme, which catalyzes the first step of the biosynthesis of PGG2 from arachidonic acid. COX isozymes exist at least in two isoforms, COX-1 and COX-2.The constitutive COX-1 isozyme is found in plateletes, kidneys, and the gastrointestinal tract and is believed to be responsible for the maintenance of physiological functions such as gastro protection and vascular homeostasis. In contrast, the COX-2 enzyme is the inducible isoform that is produced by various cell types upon exposure to cytokines, mitogens, and endotoxins released during injury and therefore molecules that inhibit its enzymatic activity would be of therapeutic value. The gastrointestinal side effects associated with NSAIDs are due to the inhibition of gastroprotective PGs synthesized through the COX-1 pathway. Thus, selective inhibition of COX-2 over COX-1 is useful for the treatment of inflammation and inflammation-associated disorders with reduced gastrointestinal toxicities when compared with NSAIDs. The recent market withdrawal of some coxibs such as rofecoxib and valdecoxib due to their adverse cardiovascular side effects clearly delineates the need to develop alternative structures with COX-2 inhibitory activity. For this reason novel scaffolds with high selectivity for COX-2 inhibition need to be found and evaluated for their anti-inflammatory effects. As a result, in this study, new methyl4-hydroxy-1-alkyl-2-aryl 5-oxo 2,5-dihydropyrrole-3-carboxylate derivatives were designed and sythesized based on the structure-activity relationship of selective COX-2 inhibitors. A mixture of 4-methylthiobenzaldehyde, arylamine derivatives and para-toluene sulfonic acid (PTSA) as a catalyst in ethanol was stirred at room temperature for 1 hour until a white precipitate appeared. Then, dimethylacetylenedicarboxylate (DMAD) was added. The reaction was stirred at room temperature until a new precipitate appeared. Finally, the resulting precipitate was recrystallized with ethanol. In the next step, a solution of Oxone in water was added to a well-stirred solution of the resulting product and diethyamine as a catalyst in acetonitrile. After the completion of the reaction, the precipitates were filtered and recrystallized with ethanol. All the target compounds were synthesized in good to high yields and the chemical structures were confirmed by IR, 1HNMR and Mass spectra. A novel series of methyl4-hydroxy-1-alkyl-2-aryl 5-oxo 2,5-dihydropyrrole-3-carboxylate derivatives was designed and synthesized as selective COX-2 inhibitors in good yields. The target compounds were characterized via IR, 1HNMR and Mass spectroscopies. The COX-2 inhibitory activity of the target compouds is under investigation

Detecting Factors Effective in Knowledge Sharing Model Among Educational Staff

One of the effective organs in implementing economic, social and cultural development policies in each country is the Ministry of Education, which trains specialized and experienced manpower as the basis for the comprehensive development of countries, production of knowledge and research knowledge, and the provision of specialized services by universities and higher education centers. Accordingly, it facilitates sharing knowledge and identifying factors affecting it in the education organization, especially among employees who are the most important elements in any organization. Because it can create an atmosphere full of trust and interaction, the employees can share their knowledge and experiences with each other; hence, it can be an important strength for the education organization as well as society. In this regard, the present study aimed to identify the factors affecting the knowledge sharing model in individual, organizational, environmental, and extra-environmental dimensions among educational staff. The study revealed that the main individual dimension includes enjoyment of knowledge sharing, organizational commitment, specific organizational knowledge, trust, motivation, value of knowledge, and individual and group interactions. Organizational dimension also encompasses organizational culture, documentation development, in-house planning and organizational rewards. The environmental dimension includes technical knowledge, information technology context, knowledge memory upgrading, and economic and social factors. The trans-environmental dimension consists of political and legal factors and international interactions. This descriptive-analytical research used a library technique

The Patency Rate of Endovascular Procedure in Patients with Superior Vena Cava Syndrome Caused by Intravenous Catheterization: A Case Series and Longitudinal Study

Introduction: Different methods have been well addressed in literature in terms of treating superior vena cava (SVC) syndrome; nevertheless, the patency of endovascular treatment has rarely been investigated in patients with SVC syndrome in patients with central venous access. Objectives: The present study was performed to assess the patency rate of endovascular procedure in patients with SVC syndrome caused by intravenous catheterization. Methods: The present case series and longitudinal study was conducted on patients with SVC syndrome in presence of central venous catheter who underwent venoplasty. Computed tomography (CT) venography was performed 1, 6 and 12 months after venoplasty. Facial swelling, facial discomfort, extremity edema, arteriovenous fistula (AVF) dysfunction, impairment in dialysis and SVC stenosis were measured at baseline and 1, 6 and 12 months after venoplasty. Results: Out of 20 investigated patients, 11 (55%) were male. Significantly decreases were observed in the median grades of facial swelling and extremity edema in the follow-up (P<0.001). The decrease in facial discomfort was statistically insignificant (P=0.129), and the median grade of SVC stenosis significantly decreased from 1.5 to zero in the follow-up (P<0.001). A statistically-significant decrease was observed in AVF dysfunction (P=0.007), and impairment in dialysis significantly decreased after the intervention during the follow-up (P<0.001). Conclusion: Findings of the present study revealed the appropriate patency rate of endovascular treatment in patients with SVC syndrome in presence of central venous catheter

Design and Synthesis of Novel Diaryl Oxo Pyrrole Derivative as Selective COX-2 Inhibitors

Inflammation is the initial defense response of the body cells and tissues to various stimuli such as pathogens, infections, irritation, chemicals, mechanical or thermal injuries.These symptoms are due to the release of some inflammatory mediators including prostaglandins (PGs). Non-steroidal anti-inflammatory drugs (NSAIDs), widely used for the treatment of pain, pyrexia, inflammation, rheumatoid arthritis and osteoarthritis, block biosynthesis of prostaglandins by inhibiting the different isoforms of cyclooxygenase enzyme (COX-1,2) . The range of activities of NSAIDs against COX-1 compared with COX-2 explains the variations in the side effects of NSAIDs at their anti-inflammatory doses. Drugs which have a high potency against COX-2 and a low COX-2/COX-1 activity ratio will have potent anti-inflammatory activity with few side effects on the stomach and kidney. The recent market withdrawal of some coxibs such as rofecoxib and valdecoxib due to their adverse cardiovascular side effects clearly delineates the need to develop alternative structures with COX-2 inhibitory activity. For this reason novel scaffolds with high selectivity for COX-2 inhibition need to be found and evaluated for their anti-inflammatory effects. Therefore in this study, novel diaryl oxo pyrrole derivatives were designed and synthesized based on the structure-activity relationship of selective COX-2 inhibitors. Target compounds were synthesized in two steps: In the first step, a solution of 4-(Methylthio)benzaldehyde, arylamine derivatives and dimethylacetylenedicarboxylate (DMAD) in the presence of para-toluenesulfonic acid (PTSA) as a catalyst, was stirred in ethanol for 72 hours. After the completion of the reaction, the resulting product was filtered off and recrystallized with ethanol. In the second step, the resulting precipitates and diethylamine were stirred in acetonitrile. Then a solution of Oxone and water was added to the mixture. After the completion of the reaction, the resulting precipitates were filtered off and recrystallized with ethanol. A series of novel diaryl oxo pyrrole derivatives were synthesized in good yields and the structure of the compounds was confirmed by FT- IR, 1HNMR and MASS spectroscopy. In this study new derivatives of diaryl oxo pyrrole was synthesized in two steps. Molecular structures of the synthesized compounds were confirmed by FT- IR, 1HNMR and MASS spectroscopy

Design and Synthesis of New Methyl 1,2-Diaryl-4-Hydroxy-5-oxo -2,5-Dihydro-1H-Pyrrole-3-Carboxylate Derivatives as Selective COX-2 Inhibitors

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation and pain is often accompanied by adverse gastrointestinal and renal side effects. Their anti-inflammatory activity results from inflammation of cyclooxygenase (COX), which catalyzes bioconversion of arachidonic acid to prostaglandins. Nowadays, it is well established that there are at least two COX isozymes, COX-1 and COX-2. COX-1 is responsible for the physiological production of prostaglandins while COX-2 is responsible for the elevated production of prostaglandins during inflammation. Thus, selective inhibition of COX-2 over COX-1 is useful for the treatment of inflammation and inflammation associated disorders with reduced gastrointestinal toxicities compared to NSAIDs. The withdrawal of some diaryl heterocyclic selective COX-2 inhibitors due to the adverse cardiovascular side effects delineates the need to explore and evaluate a new structural ring template possessing COX inhibitory activity. Therefore, in this study, new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives were designed and synthesized based on the structure-activity relationship of selective COX-2 inhibitors. Target compounds were synthesized in two steps. In the first step, 4-(methylthio)benzaldehyde, arylamine derivatives, and dimethylacetylenedicarboxylate (DMAD) in the presence of para-toluene sulfonic acid (PTSA) were stirred in ethanol for 72 hours. After the completion of the reaction, the resulting product was filtered off and recrystallized with ethanol. In the second step, a solution of Oxone and water was added to a well-stirred solution of the resulting product and diethylamine in acetonitrile. After the completion of the reaction, the resulting precipitates were filtered off and recrystallized with ethanol. In this study, new derivatives of new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate were designed, synthesized, and purified. The structure of the synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. We designed and synthesized some new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives as selective COX-2 inhibitors. The structure of synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. The COX-2 inhibitory activity of these compounds is under investigation

The Patency Rate of Endovascular Procedure in Patients with Superior Vena Cava Syndrome Caused by Intravenous Catheterization: A Case Series and Longitudinal Study

Introduction: Different methods have been well addressed in literature in terms of treating superior vena cava (SVC) syndrome; nevertheless, the patency of endovascular treatment has rarely been investigated in patients with SVC syndrome in patients with central venous access. Objectives: The present study was performed to assess the patency rate of endovascular procedure in patients with SVC syndrome caused by intravenous catheterization. Methods: The present case series and longitudinal study was conducted on patients with SVC syndrome in presence of central venous catheter who underwent venoplasty. Computed tomography (CT) venography was performed 1, 6 and 12 months after venoplasty. Facial swelling, facial discomfort, extremity edema, arteriovenous fistula (AVF) dysfunction, impairment in dialysis and SVC stenosis were measured at baseline and 1, 6 and 12 months after venoplasty. Results: Out of 20 investigated patients, 11 (55%) were male. Significantly decreases were observed in the median grades of facial swelling and extremity edema in the follow-up (P<0.001). The decrease in facial discomfort was statistically insignificant (P=0.129), and the median grade of SVC stenosis significantly decreased from 1.5 to zero in the follow-up (P<0.001). A statistically-significant decrease was observed in AVF dysfunction (P=0.007), and impairment in dialysis significantly decreased after the intervention during the follow-up (P<0.001). Conclusion: Findings of the present study revealed the appropriate patency rate of endovascular treatment in patients with SVC syndrome in presence of central venous catheter

Survey of the risk factors of hydatid cyst infection in Lordegan area of Chaharmahal and Bakhtiari province of Iran, 2004

چکیده: زمینه و هدف: کیست هیداتیک یکی از بیماریهای مشترک بین انسان و دام است که از شیوع نسبتا گسترده ای در دنیا برخوردار می باشد. استان چهارمحال و بختیاری به دلیل وجود شغل دامپروری یکی از نقاط بالقوه پر خطر این بیماری است. با توجه به اینکه شهرستان لردگان دارای شیوع بالایی از آلودگی در استان می باشد، این مطالعه با هدف بررسی میزان آگاهی از عوامل خطر ابتلاء به کیست هیداتیک در این شهرستان مورد بررسی قرار گرفته است. روش بررسی: در یک مطالعه توصیفی – تحلیلی از بین تمام افراد بالای 15 سال شهرستان لردگان 500 نفر به روش چند مرحله ای تصادفی انتخاب شدند. پرسشنامه خود ساخته حاوی سؤالاتی در مورد عوامل خطر ابتلا به بیماری در اختیار آنها قرار گرفته و تکمیل گردید. همچنین 30 قصاب از مناطق مختلف این شهرستان انتخاب و پرسشنامه شامل موارد نگهداری سگ توسط قصاب ها و امکان تغذیه سگ به وسیله احشاء آلوده تکمیل گردید. اطلاعات به دست آمده از پرسشنامه ها با استفاده از آزمون کای دو تجزیه و تحلیل گردید. یافته ها: در این مطالعه میزان آگاهی از نحوه انتقال بیماری 2/7 و میزان استفاده از آب لوله کشی 2/88 بوده است. همچنین در 4/54 موارد سبزیجات بصورت مؤثر شستشو داده می شدند. میزان نگهداری سگ در منزل 4/22، نگهداری دام در منزل 6/42، وجود سگ ولگرد در محل سکونت 6/75 بود. وجود سگ در محل قصابی ها 30 و ‌تغذیه سگ ها با احشاء دام ها 20 بود. 40 قصابان برای سهولت جدا کردن پوست در زیر آن می دمیدند. نتیجه گیری: با توجه به نتایج این بررسی که نشان می دهد سطح آگاهی مردم و قصاب ها در حد پائینی است به نظر می رسد که این افراد از نظر عوامل خطر بیماری کیست هیداتیک بایستی مورد آموزش قرار گیرند

The immunity status of the rural pregnant women in Chaharmahal and Bakhtyari province against Toxoplasma infection, 2001-2002

زمینه و هدف: امـروزه اهمیت اجتماعی، اقتصـادی پیامـدهای خطیـر ناشـی از وقـوع توکسـوپلاسموزیس مـادرزادی در انسان موجب گردیده تا بخش وسیعی از پژوهش ها به پیشگیری از عفونت های اولیـــه توکسوپلاسمایی در زنان بــــاردار و کاستن از خطر عـــوارض بیمـاری در جنین اختصاص یابــــد. این مطالعه با هـــدف آگاهی از وضعیت ایمنـــی زنان باردار 45-15 سالـــه ی روستایی در مقابـــل توکسوپلاسما گوندی ای (Toxoplasma gondii) انجام گرفت. روش مطالعه: در این مطالعه 394 نمونه سرمی با استفاده از آزمون ایمیونوفلورسانس غیرمستقیم Test IFAT (Indirect Immunofluorescence Antibody) مورد آزمایش قرار گرفت. نتایج: در کمتر از یک سوم از جمعیت مورد مطالعه (4/27) سطوحی از آنتی بادی های ضد توکسوپلاسمایی تام (Total Anti Toxoplasma Antibodies) یافت گردید که عیار آن بین 1600/1-50/1 متغیر بود. در این مطالعه تنها آنتی بادی یافت شده در سرم افراد مورد مطالعه از رده IgG بود. اگر چه در این مطالعه بین شیوع عفونت توکسوپلاسمایی و مصرف سبزیجات خام همبستگی آماری آشکاری اثبات گردید (05/0 P). نتیجه گیری: بنابراین تصور می گردد در این استان بخش عمده ای از زنان باردار و یا زنانی که در سنین باروری قرار دارند به علت عدم مواجهه قبلی با ارگانیسم در مقابل ابتلاء به بیماری در آبستنی های بعد حساس باشند