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Identification of New Anti-Glaucoma Agents With Emphasis on the Inhibition of Carbonic Anhydrase Enzyme

Thesis Info

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Author

Shama Qaiser

Institute

Virtual University of Pakistan

Institute Type

Public

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Software Engineering

Language

English

Link

http://vspace.vu.edu.pk/detail.aspx?id=160

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676720982035

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Carbonic anhydrase is metal-containing enzyme that contains Zn and involves the carboxylation of water into carbonic acid, which normally converts into bicarbonate and protons Carbonic anhydrase inhibitors (CAIs) are utilized to lower the intraocular pressure (IOP) in glaucoma condition and also decrease the inflammation associated with increasing ocular hemodynamics, and ocular apoptosis. During the course of research period, a number of synthesized compounds were analyzed by bovine carbonic anhydrase-II (bCA-II) for development of new inhibitors. For this purpose high throughput biochemical mechanism based assay was employed for the identification of new inhibitors of CA-II enzyme. Spectra max-340 and M2 spectrophotometer from Molecular Devices (USA) were used to measure the inhibition potential through absorbance. Out of numerous classes of compound only schiff bases of triazole, tosylhydrazone (sulfonohydrazone), benzylidene and thiourea derivatives, were found to be good inhibitors of CA-II. The identified inhibitors were subjected to IC50 determination by serial dilution. The Ez-fit enzyme kinetics soft were employed to calculate the IC50 values from the % inhibition. The benzylidene derivatives exhibited. IC50 values in the range of 52.68 ? 0.47 to 348.57 ? 3.32 ?M. Schiff Bases of triazole derivatives have shown IC50 values between 98.23 ? 1.60 to 285.87 ? 2.67 ?M. While thiourea derivative exhibit excellent inhibition potential which illustrated IC50 values in the range of 1.90 ? 1.30 to 25.90 ? 2.05 ?M when compared with the standard inhibitor acetazolamide IC50 = 0.13 ? 0.05. Among all the compounds thiourea derivatives can serve as lead compounds for the identification of new inhibitors of CA-II.
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پنڈت ہردے ناتھ کنزرو

پنڈت ہردے ناتھ کنزرو
یہ سطریں لکھی جارہی تھیں کہ پنڈت ہردنے ناتھ کنزرد کی وفات کی خبر ملی، انھوں نے بڑی لمبی عمر پائی، نوے سال کے تھے، وہ ایک جلیل القدر، مرنجان مرنج، بامروت، وضعدار شخصیت، پارلیمانی دستور کے بڑے ماہر ہندو مسلمان کی ملی جلی تہذیب کے عمدہ نمونہ اور اردو زبان کے بڑے محسن کی حیثیت سے برابر یاد کئے جائیں گے، وہ اپنی ترشی ہوئی بھلمنساہت کی وجہ سے ہندوستان کی سیاست کی جذباتی ہم آہنگی کے قابل تقلید نمونہ بن سکتے ہیں، بشرطیکہ موجودہ قومی دھارے کے بنانے والے ان کو ایسا ہی سمجھیں۔ (’صباح الدین عبدالرحمن، اپریل ۱۹۷۸ء)

اندلس میں مسلمانوں کے ادوار حکومت کا تحقیقی و تنقیدی جائزہ

The golden Islamic history cannot be completed without the mention of Spain which was a bright star. It became one of the great Muslim civilizations; reaching its summit with the Umayyad caliphate of the tenth century. The heartland of Muslim rule was Southern Spain or Andulus. Different eras of Muslim rule in Andulus have been described in this research with an aim to highlight their apex and glory they achieved and then a focus on the reasons of their downfall as well. A brief introduction of the rulers in all eras with their major achievements and immersion in evil habits that led to their downfall has been the prime focus of this research. It gives us various glimpses from the course of history to reflect upon Muslim rule in Spain from a new perspective.

Association of Vitamin D Receptor Genetic Polymorphism to the Type 2 Diabetes Mellitus in Local Populaion

Type 2 diabetes mellitus (T2DM) is an increasingly common metabolic disorder with a substantial inherited component. The inheritance pattern is complex and polymorphisms of several genes might influence genetic susceptibility of the disease that is characterized by islet dysfunction and insulin resistance. Although various characteristics of diabetes mellitus in local population have been investigated, progress in defining genetic factors is meager. As the genetic architecture of T2DM may vary between diverse ethnic populations, it is critical that such variants are examined in Pakistani population. The present project was aimed to investigate association of vitamin D receptor(VDR) gene polymorphisms with T2DM in Pakistan. Methodolgy included documentation of demographic charateristics and comparative analysis of biochemical parameters (glucose, HbA1c, vitamin D, lipid profile, liver function tests and renal function tests)in diabetic and normal participants. Genomic DNA was used for genotyping of four restriction fragment length polymorphism (RFLP) sites; BsmI, ApaI, TaqI and FokI by polymerase chain reaction (PCR) amplifications and restriction endonuclease digestion of the products. The digested PCR products were separated on agarose gel electrophoresis. Among all the demographic parameters, systolic and diastolic blood pressure and BMI (body mass index) were significantly higher (p<0.001) in diabetic group as compared to the control group. Hyperglycemia, renal and lipid profiles were significantly inversely associated (p<0.01) to vitamin D levels in T2DM subjects.Differences of FokI, BsmI and TaqI genotypes of VDR gene were significant between T2DM and normal groups (p<0.01).While ApaI showed non-significant association to the T2DM in local population. No significant association was found between biochemical parameters and all four restriction sites (ApaI, BsmI, FokI and TaqI) (p>0.01). In addition, VDR gene polymorphisms were related non-significantly (p>0.05) to the diabetic complications in the present study. To conclude, VDR gene polymorphisms (BsmI, FokI and TaqI) may contribute to the onset and progression of T2DM in local Pakistani population but association between VDR genetic polymorphisms to various diabetic complications is still not clear and warrants additional functional genomics studies to verify the genetic susceptibility of VDR gene to T2DM onset and progress.