ڈاکٹر ڈی ، اے ، اسمتھ
ماہ گذشتہ میں آکسفرڈ سے ڈاکٹر ڈی، اے، اسمتھ، ال، ڈی کی وفات کی خبر موصول ہوئی ۔ ڈاکٹر موصوف مشرقی علوم سے خاص شغف رکھتے تھے، اور تاریخ ہند کے ایک مستند عالم سمجھے جاتے تھے۔ تقریباً ۱۸۷۰ء میں وہ ہندوستان میں ایک سویلین کی حیثیت سے آئے تھے، اور صوبہ متحدہ کے مختلف اضلاع میں مختلف مناصب پر فائز رہ کر کوئی بیس سال ہوئے پنشن لے کر وطن واپس گئے۔ ہندوستان کے سی (۳۰) سالہ قیام میں وہ نادر سکہ جات، کتبات وغیرہ بیش بہا تاریخی مواد فراہم کرتے رہے اور ملازمت سے سبکدوش ہونے کے بعد انھوں نے تاریخ ہند پر متعدد تصانیف شایع کیں، مثلاً اکبر اعظم، راجہ اشوک کا دورِ حکومت، وغیرہ جن میں سے بعض کتابیں ہندوستانی یونیورسٹیوں کے اعلیٰ نصابِ درس میں بھی داخل ہیں، ان کی آخری ضخیم تصنیف ’’آکسفرڈ ہسٹری آف انڈیاــ‘‘ حال ہی میں شایع ہوئی تھی۔ رایل ایشیاٹک سوسائٹی نے تمغوں اور دیگر اعزازات سے ان کی علمی خدمات کا بار بار اعتراف کیا تھا۔ (مارچ ۱۹۲۰ء)
The concept of freedom and equality enshrined in democratic systems though solves certain individual problems, but at the same time many collective problems arise. In this context, these democratic values become inconsistent with principles of Islamic political system because the concept of freedom and equality in Islam is different from that in western democracy. The Islamic Sharīʻah has divided the obligatory duties into Ḥuqūqul Allah and Ḥuqūq-al-ʻIbād and complying with them guarantee the success in this world and the hereafter. Islam not only connects rights and responsibilities with each other, but also determines their priorities. Those societies where an imbalance is created in discharging duties and rights get caught up in mischief and trouble as an unavoidable consequence as if human beings play the main role in the construction and destruction of societies. Keeping in mind the above mentioned issues, the reality of modern philosophy of human rights and its basic criterions and effects in Islamic perspective has been reviewed to find the causes of failure of modern philosophy in protecting the human rights in the contemporary era. Similarly, explaining the concept of human rights in Islam in modern perspective, a research-based analysis has been presented in this paper.
The presence of heavy metals especially arsenic and lead in drinking water above the normal level (WHO standards) has threatened the use of ground water as major source of drinking water. According to different reports, majority of water wells in urban areas of Pakistan have arsenic level above the WHO recommended level of 10 ppb. In addition high level of lead is also reported especially in areas which are close to highways. Both arsenic and lead pose serious health threat to mankind as they disrupt the function of many important tissues and organs of the body. The acute and chronic arsenic exposure results in damage to digestive, cardiovascular and nervous system and also leads to many malignancies. Lead also leads to many abnormalities and especially effect nervous system. In addition, it mainly affects skin and kidney and disrupts their normal function. Lead is also possible human carcinogen and leads to malignancies of lung and stomach etc. Stem cells are type of undifferentiated cells that have the potential of self-renewal and differentiation into specialized cells. On the basis of their origin and differentiation potential they are categorized as embryonic stem cells (ESCs) and adult stem cells. Mesenchyaml stem cells (MSCs) are adult stem cells that have differentiation potential into adipocytes, chondrocytes and osteoblasts etc. In this dissertation, the effect of arsenic and lead has been described on the MSCs and differentiation of MSCs into osteoblasts at molecular level. MSCs were isolated from mice (mMSCs) and rat (rMSCs) bone marrow by simply flushing them out, and from human (hMSCs) bone marrow by density gradient centrifugation and growing them on the basis of plastic adherence. The adult MSCs (AMSCs) were isolated by enzymatic digestion of human adipose tissue whereas human fibroblasts (hFib) were isolated by explant and enzymatic digestion. The stemness of hMSCs was checked by colony forming unit assay. The doubling time of all the cells lines was checked by growing them in 6 well plates for 5 days and counting the cells everyday by hemocytometer. The doubling time of mMSCs, rMSCs, hMSCs and AMSCs was 44.32, 47.93, 60.79 and 58.59 h, respectively. The cytotoxicity assays were done by neutral red method for all the cell lines, in which 5 x 103 cells were exposed to arsenic (0-10 μg/ml) and lead (0-100 μg/ml) for a total period of 6, 12, 24 and 48 h, LC50 values were calculated. The LC50 values of arsenic against mMSCs were 2.4, 2.8, 3.4 and 3.6 μg/ml on exposure to arsenic for 6,12, 24 and 48 h, respectively, while for all other cell lines mixed results were obtained. The LC50 values for arsenic obtained were 2.5, 2.8, 3.5 and 3.5 μg/ml for rMSCs, 8, 7, 5, and 2.5 μg/ml for hMSCs, 7.6, 4.6, 4.1 and 4.8 μg/ml for AMSCs, and 9, 4, 3.8 and 3 μg/ml for hFib on exposure to arsenic for 6, 12, 24 and 48 h, respectively. The maximum reduction in proliferation of cells on exposure to lead was observed in mouse and rat MSCs. In the case of mMSCs the percentage reduction was 43, 30, 46 and 24 while it was 43, 32, 48 and 30 in the case of rMSCs. The percentage reduction was 16, 23, 28 and 6 in hMSCs, 21, 14, 12 and 16 in AMSCs and 26, 37, 32 and 28 in hFib on exposure to lead for 6, 12, 24 and 48 h, respectively. The effect of metals on morphology of cells was observed under microscope and on exposure to arsenic, cells became round in shape and were detached from plate surface, whereas in the presence of lead the effect was not as drastic as that of the arsenic and attached cells were observed even on exposure to 100 μg/ml lead. The genotoxic effects of arsenic was investigated by comet assay in which all the cell types were exposed to arsenic (1 μg/ml) and lead (10 μg/ml) for 12 h and then slides were prepared and genotoxity was checked by observing different comet parameters (Comet length, height, area, intensity, head diameter, tail length, tail area, % DNA in tail, tail moment, % DNA in head). The comet assay results showed that there was maximum DNA damage on exposure to arsenic whereas the DNA fragmentation was less in the case of lead. No DNA damage was observed in the case of control samples. Both arsenic and lead proved to have genotoxic effects on all the cell lines used in the present study. For differentiation of mMSCs, cells were exposed to 50 μg/ml ascorbic acid, 10 mM β-glycerophosphate and 1 x 10-7 M dexamethasone. Alkaline phosphatase (ALP) activity, total protein and expression profile of proteins was analyzed at different time intervals. Alizarin Red S staining was done after 21 days in the differentiation medium. The differentiation of mMSCs was done both in the presence and absence of dexamethasone. There was more than 3 fold increase in ALP activity in differentiating cells compared with the control cells. The control cells had greater concentration of total protein and more number of cells compared to differentiating cells. Dexamethasone significantly enhanced the proliferation of cells. After 21 days of growth, both in the presence and absence of dexamethasone, there was mineral deposition and differentiated cells stained red when treated with Alizarin Red while control cells didn’t stain red. SDS-PAGE did not show any difference in expression of protein in control and differentiating cells. The proliferation of cells was greatly reduced when hMSCs were grown in the differentiation medium with arsenic (100 ng/ml) and lead (1μg/ml). The ALP activity increased gradually in the differentiation medium with or without metals compared to control cells. The difference in ALP activity was very less among the differentiating cells and metal exposed differentiating cells but it was high compared to control cells. The differentiating cells stained red with Alizarin Red but in the presence of arsenic and lead, the cells did not stain red. On crystal violet staining the morphology of cells changed from spindle to oval in the differentiation medium. In the presence of arsenic, the morphology of cells was totally changed. Dendrites like out growth were observed (blebbing phenomenon), while in the presence of lead the morphology of cells was comparable to differentiated cells. The expression of two marker genes of stemness, Oct4 and HLA-DR alpha were detected in the stem cells but were absent in the control cells (fibroblasts). Beside that the expression of differentiation markers, osteocalcin, osteopontin, osteonectin, Runx2, BMP2, ALP and collagen were found to increase in the differentiation medium with and without lead, whereas the expression of BMP2 and Runx2 remained the same. The effect of arsenic could not be detected due to high cytotoxicity and genotoxicity. The cells died rapidly and good quality RNA could not be isolated for further analysis. No change was observed in protein pattern of cells in the differentiating medium with and without metals. The expression of apoptosis related genes including Bax, Bcl-2, c-myc and P53 were monitored in the cells exposed to 100ng/ml arsenic and 1 μg/ml lead for 12 h. The expression of P53 gene only was detected in arsenic exposed cells which indicated that arsenic triggers the apoptosis pathway of cells and results in death of cells. To conclude, MSCs were isolated from a different source on the basis of their adherence potential to plastic surfaces and differentiated into osteoblasts using standard differentiation protocol. mMSCs, could be differentiated into osteoblasts like cells even in the absence of dexamethasone, which is a key component of osteoblast differentiation medium. Arsenic and lead proved to have both cytotoxic and genotoxic effects on all the cell types used but arsenic proved to be much more toxic than lead. In addition, both arsenic and lead have adverse effects on the morphology of cells. Longer exposure to arsenic resulted in blebbing outgrowth of plasma membrane. The exposure of differentiating cells to arsenic and lead at 1 μg/ml and 10 μg/ml respectively did not significantly affect the expression of differentiation marker genes. At molecular level both metals severely affected the differentiation process so the exposure of these metals especially in early age can result in several bone abnormalities. According to reports from environmental protection department (EPD), the level of arsenic and lead is increasing in drinking water all over the country so there is great need to figure out sources of water contamination and proper measures should be taken to reduce the exposure of people to these heavy metals." xml:lang="en_US