اسلامی ریاست میں داخلی استحکام کے لیے مرکز اور صوبوں کے تعلقات

There is a dire need of an experienced and authoritative mechanism in the polity of Islām in order to run the affairs of the state in a benefiting manner. This mechanism divides the state into different regions and provinces so as to carry out the affairs of the state in an organized way. These provinces must be founded on some administrative basis, not on racial, lingual or regional grounds. It is necessary that these units are autonomous as far as authority and power is concerned. It will help eradicate parochial differences and strengthen integrity of a country. It is essential to keep up and safeguard the freedom and the rights of these units. We can get our desired objectives, if legal and constitutional safeguards are meted out to these administrative units of the state. According to ‘Allāmah Ibn Khaldūn’s point of view, it is imperative to strengthen a state instead of expanding it. There must be small but integrated autonomous units of the state. Such division helps these units to progress and prosper. The golden principle of power distribution is in vogue in all eras, although its structure has been different and varied. In this article, we are going to view the structure of distribution in the perspective in an Islamic state

Biological Properties, Clinical Implications and Role As Oxidative Biomarker of Human Paraoxonase

Oxidative stress reflects an imbalance between production of oxidizing species and their removal through antioxidant system. This imbalance is harmful for biological macromolecules like proteins, lipids and DNA. Oxidative stress has been implicated in pathophysiology of many diseases. To counteract the harmful effects produced due to over production of reactive oxygen species, living organisms are equipped with antioxidant defense mechanism. Paraoxonases (PON) are calcium bound enzymes having antioxidant properties. The PON family constitutes three isoforms including PON1, PON2 and PON3. Among these, PON1 is the most studied member with defined antioxidant property. Reduced PON1 activity has been reported in various disorders including Cataract. Cataract is third most prevalent age related disease responsible for blindness throughout the world. One of the key factors involved in progression of cataract formation is oxidative stress. Another possible contributor is accumulation of advanced glycation end products (AGEs) leading to non-enzymatic glycation of macromolecules particularly proteins. AGEs formation is not only accelerated in presence of hyperglycemia but also triggers production of reactive oxygen species leading to glycoxidation. Thus, interplay of both oxidative imbalance and glycation may play critical role in etiology of cataract. Objective of current study was to explore biological properties, clinical implications and role of Paraoxonase as oxidative biomarker. We chose cataract as a model disease to examine PON family members. Partial purification of PON enzyme was performed using human plasma through affinity and gel filtration chromatography. Partially purified samples were further subjected to SDS-PAGE and MS analysis. The fraction with highest PON1 activity was found to be albumin through mass spectrometric analysis. Our studies confirm that PON1 has a greater affinity for albumin and may exist in association with albumin. PON gene polymorphism has been studied to examine association between genetic variant with incidence of diseases. In current study, we examined PON gene polymorphism for PON1 (L55M & Q192R); PON2 (C311S & G148A) and PON3 (C133A) in normal and cataract subjects using tetra primer ARMS-PCR and RFLP followed by agarose gel electrophoresis. Polymorphic sites 192R of PON1 and G148 of PON2 were found to be more frequent in cataract patients as compared to normal xi individuals suggesting these alleles to be disease specific in studied samples of Pakistani origin. Combine genotype analysis revealed L55/Q192 of PON1 and C311S/ 148A of PON2 in healthy individuals while G148/311S of PON2 among cataract subjects to be significant. PON1 L55M, PON2 C311S and PON3 did not show significant association with cataract. To explore the impact of glycation on PON1 and its biological activity, we incubated plasma from normal and cataractous subjects with sugars (glucose, fructose & galactose) for 15 days. Enzymatic activities (Paraoxonase and arylesterase) along with oxidative stress markers MDA and total ROS were measured. Time dependent structural changes in response to glycation were monitored through spectroscopic analysis while level of glycation was measured by AGEs quantification through ELISA. Our results indicated significant decrease in paraoxonase and arylesterase activities together with substantial increase in MDA and total ROS levels among all incubated samples. Most potent sugar was found to be fructose followed by galactose than glucose. The degree of glycation was found to be in order of fructose>galactose>glucose. To confirm the effect of fructose on PON1 activity, pure PON1 was incubated with fructose which showed 95% decline in PON activity as compared with respective control. In conclusion, our study highlights impact of polymorphism and genetic variation among PON family members in studied groups, biological role of PON1 as an antioxidant in response to glycation and implication of glycation on PON1 activity.