In the current scenario, one of the most key health issues in the world is inflammation. Inflammation is a body defense mechanism. It is the local response of living tissues to injury in order to eliminate or limit the spread of injurious agent. Heat, redness, swelling, pain, and loss of function are the main symptoms to identify it. That involves three phases like vasodilatation, phagocytic migration and tissue repair. Many medications like non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are available to prevent or minimize the progression of the inflammatory diseases. NSAIDs are associated with several side effects. Their prolonged use may causes bone marrow depression, gastric intolerance, kidney failure, water and salt retention, liver failure, ulcers and prolonged bleeding after an injury or surgery. Thus, most antiinflammatory drugs have a number of adverse effects hence there is a need to develop a safe and new anti-inflammatory drug with minimum side effects. On the other hand, cyclic imides possess structural features which conferred potential biological activity and pharmaceutical use. The various classes of cyclic imides have received greater attention due to the COX-2 inhibition, anti-inflammatory activity. Based on this, we synthesized various ketone and ketoester derivatives of succinimides. Among the synthesized compound total of ten (10) compounds were newly synthesized. All the compounds obtained were purified with pen/pencil column. The pure compounds obtained were identified with various techniques i.e., mass spectroscopy, carbon NMR and proton NMR. After confirmation of their structure, they were subjected to in-vitro anti-inflammatory assay using cyclooxygenase (COX-2) and 5- lipoxygenase (5-LOX) enzyme. In COX-2 in-vitro enzyme inhibitory assay, compound SJ-17, SJ-15 and SJ-2 were the most potent compound that displayed IC50 value of 0.98, 2.10 and 19.98 μM respectively. While in ketoesters derivatives of succinimides the tested compound SJ-18 and SJ-22 were displayed the most potent activity against COX-2 enzyme with IC50 value of 61.07 and 43.21 μM. In 5-LOX in-vitro enzyme inhibition assay SJ-17 and SJ-13 were more potent with IC50 values of 0.86 and 0.81 µM respectively. The tested compound SJ-2 and SJ-11 also showed the best activity with IC50 value of 36 and 21.31 µM. While in ketoester derivatives the SJ-22 displayed excellent 5- LOX inhibition with IC50 of 33.57 µM respectively. All the synthesized compounds were then subjected to preliminary in-vivo anti-inflammatory study to confirm the anti-inflammatory effect. In carrageenan induced paw edema three doses of each tested compounds were applied. Among the tested compounds SJ-17 was the most potent and significantly inhibited the inflammation produced by carrageenan up to 55.17 ± 1.36 % after 1 h at 100 mg/kg. The maximal percent inhibition of paw edema was observed to be 68.22 ± 2.44 at 5th h. Second highest activity was displayed by SJ-11 with 61.97 ± 3.24 % inhibition. Likewise, tested compounds SJ-2 and SJ-22 also exhibited excellent activity with 55.07 ± 2.33 and 54.77 ± 1.55 % inhibitions at 100 mg/kg body weight (b.wt). Aspirin was used as a positive control in this assay which displayed 57.64 ± 1.55 % inhibition. The other entire synthesized compounds displayed moderate to good activity in carrageenan induced inflammation. In arachidonic acid induced ear inflammation, again SJ-17 was the most potent compound with 76.70 ± 2.24 % inhibition of ear edema at 100 mg/kg b.wt. While tested compound SJ-11 exhibited 63.88 ± 2.66 % inhibition. The tested compound SJ-2 and SJ-22 displayed 56.30 ± 1.24 and 63.81 ± 1.24 % activity. All the other compounds in this assay illustrated moderate to good activity. Furthermore, based on the in-vitro and in-vivo preliminary anti-inflammatory results the potent compounds were subjected to various inflammatory mediators like histamine, bradykinin, prostaglandin (PGE2) and leukotriene for the mechanism confirmation of the synthesized compounds. The compounds SJ-2, SJ-11, SJ-17 and SJ-22 were found to be the most effective among all the synthesized compounds. In histamine induced inflammation, tested compound SJ-17 has shown good activity (34.86 %, at 2nd h). The other tested compounds SJ-2, SJ-11and SJ-22 were less effective with 17.19, 25.38 and 11.11 % inhibition in this assay. The positive control cetirizine displayed 71.64 % inhibition. In bradykinin induced paw edema test SJ-2, SJ-11, SJ-17 and SJ-22 exhibited less activity while causing 7.37 ± 1.10, 4.42 ± 1.89, 15.28 ± 2.19 and 9.72 ± 3.13 % inhibition at 1st h. While the antagonist icatibant (HOE 140) showed dose dependent and significant inhibition 65.54 ± 3.61 % after 1 hour and remained significant until 5th h. Whereas, in prostaglandin E2 (PGE2) inflammatory mediator tested compound SJ-17 was the most potent and dose dependent causing 81.08 ± 2.03 % inhibition at 4th h. Similarly, SJ-11 exhibited 72.03 ± 3.24 % activity at 4th h which was the second active compound in this study. Likewise, the SJ-2 and SJ-22 also give excellent results with 64.33 ± 1.59 and 51.87 ± 3.24 % inhibitions at 4th h after the injection of phlogistic agent PGE2. Moreover, in leukotriene induced inflammation assay, the tested compound SJ-17 was again potent and give a promising result with 74.11 ± 3.58 % inhibition. SJ-11 was the second high active compound causing 58.13 ± 2.25 % inhibition. The tested compound SJ-2 was exhibited 49.08 ± 2.93 % activity while SJ-22 is less effective as compared to other tested compounds and exhibited 38.41 ± 3.07 % activity. From the current investigation it is clear that the compounds SJ-17, SJ-11 and SJ-2 have been verified to combat inflammation especially dual inhibition of COX-2 and 5-LOX. And inhibited both lipoxygenas as well as cyclooxygenase pathways of arachidonic acid metabolites supported by the mild anti-histaminic effect. So further work should be performed by the dosage form designing for these compounds to hit the market.
کتب کو مرتب کرنے کا سلسلہ قدیم زمانے سے چلا آ رہا ہے ایسی کتب کے بے شمار پہلو اور فوائد ہیں۔پہلی بات کہ کسی خاص موضوع پر بہترین تخلیقات پڑھنے کو ملتی ہیں۔دوسری بات بہت سارے تخلیق کاروں کے بارے میں معلومات ایک ہی کتاب میں سے مل جاتی ہیں ،تیسری بات مرتب کنندہ کے مزاج کے بارے میں پتہ چلا جاتا ہے۔چوتھی بات وہ تخیق کار جن کی تخلیق کا دائرہ زیادہ وسیع نہیں ہوتا۔جس کے باعث وہ اپنے کاتم کو شائع کروانے سے قاصر ہوتے ہیں۔ان کی کاوشوں کو محفوظ کر لیا جاتا ہے۔ایسی ہی ایک کوشش چوہدری نذیر احمد ارمان نے بھی کی ہے۔آپ نے پنجاب بھر کے انگریزی پڑھانے والے اساتذہ کرام کی تخلیق کردہ غزلیات میں سے انتخاب کرکے ایک کتاب ادیب انگلش ٹیچرز غزلیات مرتب کی ہے۔اس کتاب میں سولہ اساتذہ کرام کی غزلیات کو شامل کیا ہے۔اس کتاب کے شعری محاسن کچھ اس طرح سے ہیں:
ارمان صاحب نے کتاب کا نام جو تجویز کیا ہے۔وہ کسی بھی لحاظ سے ادب کے ساتھ مطابقت نہیں رکھتا۔پہلی نظر میں کتاب پڑھنے والا کتاب کے نام اور سر ورق کی تصویر دیکھ کر چونک جاتا ہے۔بادی النظر میں تصویر سے ایسا محسوس ہوتا ہے کہ اس کتاب میں پڑھانے کے طریقہ کار کے بارے میں بتایا گیا ہوگا۔
کتاب کا آغاز حسب روایت حمد باری تعالیٰ سے کیا گیا ہے۔اگر دنیا کے تمام درخت قلم اور سمندروں کاپانی سیاہی بن جائے تو اس خدا کی تعریف ختم نہیں ہوگی۔
This article exposes Updike’s use of the Qur’anic verses in his novel Terrorist. Apparently, the writer wants to investigate a Muslim terrorist’s mind, which causes him to launch deadly attacks against the American people. However, the results of Updike’s investigation are problematic and subjective. Updike seems to be a new Orientalist who manipulates the Qur’anic scripture to assert his mastery, neutrality and intolerance of Islam for non-believers. It proves that his presentation of Islam is based on stereotyped myths and lies. The narrator claims that the protagonist “Ahmad”, under the guidance of his religious teacher Sheikh Ahmed, inspired by the irrational and suppressed tone of the Qur’an, commits a suicide attack at Lincoln Tunnel but in the end, he is persuaded by his Jewish- school- councilor to discard this idea. Conclusively, it sounds that Updike fails to detach himself from his characters and misuses the Qur’anic verses to defend his pre-supposed ideology against Islam.
ABSTRACT
This study is designed to assess the targeting efficiency, evaluate the welfare impact on the lives of the poor and explore the public perceptions about the performance of Dandot Bait-ulMal (DBM), Official Zakat System (OZS) and Benazir Income Support Program (BISP). To achieve the objectives, primary data is collected from households, through a survey conducted in Dandot and Dhalwal towns of district Chakwal, province Punjab, Pakistan. A total of 800 households are interviewed by using stratified and simple random sampling techniques. To address the objectives, different measures of targeting efficiency and propensity score matching methods are employed.
The findings reveal that DBM is the most efficient program since its targeting count gap is the lowest, followed by BISP and OZS. Targeting ratio of BISP is the lowest than that of the other two programs but its beneficiaries also belong to the richest households. The results show that all programs succeed to some extent in targeting poor, however, evidence of type-I and type-II errors is found. No leakage of funds is found in DBM. The third quintile of beneficiaries of OZS doesn't receive 24.5% of funds while about one-fifth of funds are not received by the poorest segment of BISP beneficiaries. About one-third of the beneficiary households get help to register their names with programs.
The estimates of matching methods reveal that per adult equivalent food and per capita health expenditure of cash recipients are significantly higher than those of the non-recipients. The significant difference in educational expenditures is also observed between recipients and nonrecipients of DBM and BISP. The poverty status of the BISP beneficiary households is not only higher than the non-beneficiary households but also statistically significant. The cash transfer of BISP is unable to provide any relief in terms of poverty to its beneficiaries. A significant proportion of the beneficiary households feel better off as compared to their position last year. Almost all the respondents report that the DBM has the potential to overcome poverty provided that proper ‘rehabilitation schemes’ are introduced and the ‘well-to-do people are motivated to
contribute’ to the program funds. The majority of respondents suggest that the ‘allocation of funds should be raised’, and ‘survey for the identification of the poor should be properly conducted’ to improve the role of the programs. The study implies that these programs can playa vital role in improving the lives of the poverty-ridden segments of the society but it needs sincere efforts on the part of the stake-holders.