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Drug-Drug Interaction Studies of Cetirizine

Thesis Info

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Author

Shamshad, Hina

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2009

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/6496/1/3299H.pdf

Added

2021-02-17 19:49:13

Modified

2023-01-06 19:20:37

ARI ID

1676725928126

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لوکاں اگے اڑ کے ویکھے

لوکاں اگے اڑ کے ویکھے
اکھیں سفنے جڑ کے ویکھے

جیہڑا عشق نوں من دا نئیں
ساڈا ہتھ اوہ پھڑ کے ویکھے

مکھ اوہدے دا نور وے لوکو
چن وی راتی سڑ کے ویکھے

اسیں نہیں اوہدے کولوں ڈردے
نال اساڈے لڑ کے ویکھے

عشق نے انج دی حالت کیتی
ہر اک بندہ کھڑ کے ویکھے

باہروں ہسدا ویکھن سارے
کوئی تے اندر وڑ کے ویکھے

الإمام ابن خزيمة و منهجه في صحيحه

Qur’an and Prophetic traditions (Hadith) are the fundamental sources of Islam. Muslims believe that Qur’an is the word of God (Allah). Hadith (Prophet’s Sayings, actions and silent approval and disapproval for something) likewise is based on divine revelation. Qur’an affirms also this view: (God says) Your Companion (Muhammad) has neither gone astray nor has erred. Nor does He speak of (his own) desire. It is only a Revelation revealed. Al-Qur’an (53: 2-4). Allah Almighty Himself took the responsibility to guard His word (the Qur’an): (He says : ) verily, we, it is We Who have sent down the Dhikr (i.e. The Qur’an) and surely, We will got it (from corruption). (Al-Qur’an: 15: 9) on the contrary the responsibility to guard the prophetic traditions (Hadith) was put on the shoulders on the Muslim Ummah. The scholars of Islam (Ulamas) try their utmost to collect and save the Prophetic traditions and guard it from any alteration. To achieve this purpose, they introduced different hadith sciences to distinguished between the true and the fabricated hadith. The authentic Sunnah is  contained within the vast body of Hadith literature. Different scholars have compiled the books which contain a large numbers of authentic Ahadith (Ahadith Sahiha), one of them is Imam Ibn e Khuzaima. In this article we will discuss the Imam Ibn e Khuzaima approach towards “Ahadith al Sahiha” in his book “Sahih Ibn e Khuzaima”.

Modulation of Proliferation and Apoptosis Biomarkers in Oral and Other Cancers

Cancer, also known as neoplasia, involves uncontrolled cell proliferation leading to malignant tumor formation. Epithelial cancers (or carcinomas, representing about 80% of all cancers) are a group of cancers originating in the epithelial lining of many locations, such as digestive tract, airways, breast, reproductive tracts and oral cavity. Oral cancer is one of the eight most common types of cancer worldwide. It starts from the upper digestive tract, including the larynx, oral and nasal cavities. Whereas lung cancer is the major cause of cancer-related deaths worldwide, representing about 26% to 28% per year. Heavy alcohol consumption, betel nut chewing, smoking, viral infections, occupation hazard and exposure to UV radiation are the major risk factors. Tyrosine kinase receptors (TKs), such as EGFR and Lyn are major regulators of cell growth and survival. In cancer cells, such receptors are constitutively activated and lead to malignant phenotype. Blocking of active TKs efficiently stops proliferation and induces apoptosis in oral and lung cancer cells. In the present study, we selected five TKIs (Genistein, Gefitinib, Erlotinib, Dasatinib, and Imatinib) which acts upon EGFR and Src family tyrosine kinases. Imatinib and Dasatinib are non-optimal TKIs for oral and lung carcinomas, and have to be utilized at relatively high concentrations to display inhibition. Our goal was to select therapeutically suitable small molecules, such as resveratrol (a natural polyphenol) and artemisinin along with its derivatives (synthetic endoperoxides) to potentiate the sub-optimal activity of standard TKIs. The objective of our study was to investigate standard TKIs and the possible adjuvant effects of artemisinin derivatives (endoperoxides, EPs) and resveratrol (natural phenol, NP) on highly malignant lung cancer cells (NCI-H460) and laryngeal cancer cells (KCLB-SNU46) of lower malignancy. Optimal combinations of TKIs and EPs/NP that decrease the proliferative capacity of oral and lung cancer cell lines, and increase their apoptosis potential were thus investigated. The techniques employed were flowcytometry, spectrophotometry, SDS-PAGE and western blotting. Out of five TKIs, Imatinib and Dasatinib at higher concentration and on 48 hours incubation affected the oral cancer cell line (KCLBSNU46). However, the lung cancer cell line (NCI-H460) responded to Gefitinib as well as Imatinib and Dasatinib only after 48 hours. Artemisinin itself didn’t show any effect but its endoperoxide derivatives OD59 and OD66 showed potent anticancer activity (with very low IC50) in both cell lines when compared to that of the standard TKIs. Resveratrol showed no effect on oral cancer cells, but lung cancer cells did respond to high resveratrol concentrations. In combination studies, resveratrol and endoperoxides (OD66 and OD67) showed significant synergistic effects when combined with gefitinib and dasatinib at very low concentrations in both the cell lines. Furthermore it was confirmed that these synergistic combinations induced apoptosis by modulating the phosphorylation of the EGFR and Lyn tyrosine kinases. This study conclude that resistance phenomena in cancer cells can be modulated by combining sub-therapeutic doses of standard TKIs with least effective doses of natural and synthetic compounds. This approach can conveniently reduce the dosage as well as the cytotoxic effects of the clinically used TKIs on cancer patients.