لال بہادر شاستری
پنڈت جواہر لال نہرو کا غم ابھی فراموش نہ ہوا تھا کہ ملک نے ایک اور لعل بے بہا کھودیا، شری لال بہادر شاستری کی موت ہندوستان کا عظیم ترین حادثہ ہے۔ ان کی موت سے ہندوستان ایک ایسے فرزند سے محروم ہوگیا جس کی تلافی مدتوں نہ ہوسکے گی، انھوں نے ملک و قوم کی خاطر غریب الوطنی میں جان دی اور مرنے سے پہلے ایک ایسا کارنامہ انجام دے گئے جو ہند و پاک کی تاریخ میں یادگار رہے گا، مگر افسوس کہ اس کے خوشگوار نتائج اپنی آنکھوں سے نہ دیکھ سکے، پنڈت جواہر لال نہرو کی زندگی ہی میں یہ سوال پیدا ہوگیا تھا کہ ان کے بعد کوئی ایسی شخصیت نظر نہیں آتی جو وزارت عظمیٰ کے بارگراں کو سنبھال سکے، لیکن شاستری جی نے اٹھارہ مہینہ کی مختصر مدت میں یہ ثابت کردیا کہ وہ پنڈت جی کے صحیح جانشین تھے۔ اس قلیل مدت میں بڑے پیچیدہ اور نازک معاملات پیش آئے، لیکن شاستری جی نے اپنے فہم و تدبر اور ہمت و پامردی سے ان کا پورا مقابلہ کیا، معاہدہ تاشقند تو ان کے اور جنرل ایوب کے تدبر کا شاہکار ہے، گو اس سے سب مختلف فیہ مسائل حل نہیں ہوگئے، لیکن ہندوستان اور پاکستان کی ہلاکت خیز جنگ کا خاتمہ ہوگیا، اور صلح و مسالمت کی ایسی فضا پیدا ہوگئی ہے کہ اگر فریقین نے ہوشمندی سے کام لیا تو ہندوستان و پاکستان کے درمیان مصالحت اور دوستی کا خوشگوار دور شروع ہوسکتا ہے۔
شاستری جی بڑے ٹھنڈے دل و دماغ کے اور طبعاً نرم مزاج، صلح جو اور امن پسند انسان تھے، لیکن سختی کے موقع پر سخت اور ہمت و استقلال کا پیکر بن جاتے تھے، انھوں ے اپنی سلامت روی اور ہوشمندی سے ملک کو بڑے نازک حالات سے نکالا، افسوس ہے...
Today’s world is a global village. Societies affect each other far deeper and faster than ever. New problems are sprouting with every coming day. We feel that the cultural issues are the most significant ones in this context. The question is how we should deal with these problems. To us, the solution lies in the concept of Sadd al-Dharā’i‘(prevention), one of the instruments of Sharī‘ah (Islamic Law). Such is its importance as all the four schools of thought are of the same opinion about its scope. A cultural change if drives Muslims away from the objectives of Sharī‘ah, it will have to be stopped or altered to suit the objectives, but if it leads to something good without damaging the objectives of Sharī‘ah, it will be accepted. New problems are multifarious. We need to bring ijtihād into practice and solve such problems. This research article discusses the concept of Sadd al-Dharā’i‘(prevention.), its meaning, definition, and scope. It also discusses different opinions of scholars. The author of this paper, then, deliberates its use for its applications to solve the new problems being faced by the Muslims across the world.
β thalassemia is the most prevalent autosomal recessive disorder characterized by absence or reduced production of hemoglobin (Hb) levels, primarily caused by mutations on β globin locus. β thalassemia is heterogeneous at the molecular level, presenting variable phenotypes accompanied with severe medical complications. Current standard of care for clinical management of β thalassemia includes regular, long-life safe blood transfusion along with appropriate iron chelation therapy. At present, the only permanent cure is bone marrow transplantation. An emerging and exciting therapeutic approach to handle β thalassaemia is production of fetal hemoglobin (HbF) which is major Hb of fetal life. In recent years, Hydroxyurea (HU) has proven to be a promising HbF augmenting agent but response to HU therapy varies from transfusion elimination to insignificant clinical response. Various approaches are being made to understand the mechanism HbF augmentation with differential responses. Advancement in proteomics offers an efficient tool to study differential proteome in response to treatment leading towards precision and personalized medicine. This study is designed to improve mechanistic understanding of proteomic changes that HU therapy exerted on β thalassemia patients, in consort with deciphering differential protein expression in HU responder and non-responder. Firstly, samples were subjected to twodimensional gel electrophoresis to assess differentially expressed proteins. Later, differential proteins were identified by label free quantitative proteomics approach. Two hundred and eighty seven proteins were identified with two or more unique peptides in samples studied. Among these, twenty eight proteins were found to be significantly different in pre versus post HU treated β thalassemia patients at probability of < 0.05. Eighteen proteins were down-regulated while ten were found to be up-regulated after HU treatment. Clinically important proteins include Hemopexin (HPX), Haptoglobin (HP), Haptoglobin-related protein (HPR), Hemoglobin subunit beta (HBB), Hemoglobin subunit delta (HBD), Hemoglobin subunit alpha (HBA1), Protein S100-A8 (S100A8), Apolipoprotein L1 (APOL1), Apolipoprotein C-I (APOC1), Transferrin receptor protein (TFRC), Complement C4-A (C4A), Apolipoprotein A (LPA), Ceruloplasmin (CP) and Ficolin-3 (FCN3). HU therapy in β thalassemia patients started reverting protein profile towards healthy pattern, in addition with decrease in transfusion requirements. A follow up study on plasma of HU treated β thalassemia patients was performed to compare proteomic profile of HU responder and non-responder. Twenty six proteins were found to be differentially expressed in HU responder versus non-responder at p < 0.05. Among these, fifteen proteins showed a significantly increased level while eleven proteins revealed a decreased in expression. Clinically relevant altered proteins in HU responder are Peroxiredoxin-2 (PRDX2), Carbonic anhydrase 1(CA1), Hemoglobin subunit gamma-1 (HBG1),Hemoglobin subunit beta (HBB), Hemoglobin subunit delta (HBD), Hemoglobin subunit alpha (HBA1), Properdin (CFP), Cholinesterase (BCHE), Phospholipid transfer protein (PLTP) and Plasma protease C1 inhibitor (SERPING1). We suggest that further research would be required for validation of identified proteins in large cohort to endorse as potential predictive biomarker for HU therapy. Considering the association of oxidative stress with β thalassemia, we also studied markers of oxidative stress in response to HU therapy in β thalassemia covering Paraoxonase1 (PON1), Reactive oxygen species (ROS), and Malondialdehyde (MDA). Although PON1 serve as an antioxidant to reduce the adverse effects of the oxidative stress in β thalassemia, our results indicate that mode of action of HU may not directly be through oxidative imbalance