مولانا عبدالسلام ندوی
گزشتہ مہینہ مولانا عبدالسلام ندوی کی وفات اردو زبان کے علمی اورادبی حلقوں کے لیے ایک بڑا الم ناک سانحہ ہے۔مرحوم کاسب سے بڑاوصف اور کمال جس میں مشکل سے ہی کوئی اُن کاحریف ہوگایہ تھا کہ وہ صرف ایک نامور مصنف، بلندپایہ ادیب اورنقد سخن کے بہترین جوہری تھے، اس حیثیت سے وہ لیلی علم وادب کومخاطب کرکے بجاطورپر کہہ سکتے تھے کہ :
’’سب سے بیگانہ ہے اے دوست شناسا تیرا‘‘
۱۹۲۸ء میں امرتسر میں ندوۃ العلماء کے سالانہ جلسہ کے موقع پر راقم الحروف کو مولانا ابوالجلال ندوی اورمولانا نورالحق ندوی جواُس وقت نئے نئے مصر سے واپس آئے تھے ان دونوں کی معیت میں مولانا مرحوم سے ملاقات کا پہلا اورآخری بھی، شرف حاصل ہوا تھا۔یہ ملاقات جس طرح ہوئی،مولانا کو جس وضع قطع میں دیکھااوراُن سے جو گفتگو ہوئی، اگرکوئی اورہوتاتویقینا بدگمان ہوجاتالیکن میرے دل پراُس کاخاص اثر ہوا اوراُن کے فطری مصنف اورادیب ہونے کا جزم ہوگیا اوربے ساختہ زبان سے تمکین دہلوی کایہ شعر نکل گیا:
آنکھ پڑتی ہے کہیں پاؤں کہیں پڑتا ہے
سب کی ہے تم کو خبر، اپنی خبر کچھ بھی نہیں
مرحوم کی عبارت سادہ مگر شگفتہ اوربہت سلجھی ہوئی ہوتی تھی۔ جس موضوع پرگفتگو کرتے تھے اُس کے تمام پہلوؤں کامکمل تجزیہ کرکے ہرپہلو پرسیرحاصل بحث کرتے تھے، اس لیے اُن کاطرزنگارش صرف پڑھنے میں دلچسپ ودل نشین نہیں تھا بلکہ یقین آفرین بھی تھا۔مولانا شبلی نے اپنے شاگرد کے اس وصف طبعی کو پہلے ہی تاڑلیا تھا اوروہ اس کے بڑے قدران تھے۔چنانچہ اُن کے مکاتیب میں مرحوم کی نسبت جو حوصلہ افزاتاثرات وخیالات ملتے ہیں وہ اُن کے کسی دوسرے شاگرد یہاں تک کہ سید صاحب کے متعلق بھی نہیں ملتے۔ بیسوں مقالات کے علاوہ مرحوم کی مستقل تصنیفات تاریخ وفلسفہ،اخلاق،شعروادب اورتنقید سے متعلق ہیں،اردو ادب کاایسا قیمتی سرمایہ ہیں...
Hypertriglyceridemia is third prevailing cause of acute pancreatitis after biliary and alcoholic etiology. It accounts for 1 to 4% cases of pancreatitis. Present case describes a thirty years old diabetic male, who presented in emergency with pain in the abdomen and yellow discoloration of the skin. He was admitted with suspicion of diabetic ketoacidosis (DKA), but no improvement was seen after DKA treatment. His laboratory investigations showed normal serum amylase levels and dyslipidemia with raised serum triglycerides levels. He was diagnosed as acute pancreatitis secondary to hypertriglyceridemia, which is considered as a rare cause of acute pancreatitis.
Drug development has multiple stages of drug designing and evaluation in pharmacological models for desired clinical outcomes. The unmet need to completely eradicate cancer and leishmaniasis drives researchers to continue the struggle for safer and effective medicines. Along these lines, a library of 78 organic synthetic compounds including organotin (IV) (39), indoline (15), hydrazide (4), diazole (2) and ferrocene (18) derivatives were studied against Leishmania and cancer using in vitro, in silico and in vivo models. Cytotoxicity against DU145, THP-1 and isolated lymphocytes was shown by 36 (> 70%), 21 (> 50-70%), and 18 (least IC50 2.23 μg/ml) organotins and 1 (75.72%), 4 (50.2-82.3%) and 2 (least IC50 13 μg/ml) indolines, respectively. Only 5 (50.08-81.7%) hydrazides/diazoles and 9 (least IC50 6.66 μg/ml) ferrocenes were cytotoxic to THP-1 cells and lymphocytes, respectively. A total of 38 (least MIC 0.0122 μg/disc) organotins, 1 (least MIC 3.125 μg/disc) indoline, 3 (least MIC 1.5625 μg/disc) diazole/hydrazides and 17 (least MIC 0.74 μg/disc) ferrocenes demonstrated protein kinase (PK) inhibition activity in Streptomyces 85E. Next, in silico analysis of selected 36 organotin (IV) compounds, comparatively more cytotoxic to cancer cells, showed that these were drug-like to mid structures, have low to high blood brain barrier penetration and human intestinal absorption (caco2 cell permeability 17.6-35.09 nm/sec) and were metabolized by phase I and phase II reactions. Organotins were also predicted to target multiple enzymes, transcription factors, receptors, transporters, ion channels and other proteins. Subsequently, in vitro cytotoxicity analysis in prostate cancer cell lines and fibroblasts provided least IC50 values of 0.17 μM (PC3M) and 1.67 μM (fibroblasts) for triphenyltin (IV); 0.63 μM (PC3M) and 0.12 μM (fibroblasts) for tributyltin (IV); 0.33 μM (PC3M) and 2.55 μM (fibroblasts) for dibutyltin (IV) and 6.06 μM (PC3M) and 4.29 μM (fibroblasts) for tribenzyltin (IV) compounds after 72 h of treatment. Eventually, in-depth study of two most active compounds namely dibutylstannanediyl (2Z,2’Z)-bis(4-(benzylamino)-4-oxobut-2-enoate (Ch-620) and triphenylstannyl 2-(benzylcarbamoyl) benzoate (Ch-319), showed that both compounds were more cytotoxic to prostate cancer and melanoma cells as compared to normal cells, restricted their colony forming capacity and migration, induced cell cycle arrest and caspase mediated apoptosis and disrupted associated regulatory proteins. Ch-620 resulted in phosphorylation of p38 MAPK and ERK1/2, upregulation of PPARα, decreased expression of SMAD4 and ITGB5 and reduced tumor proliferation as observed by proteomics, in vitro and in vivo xenograft studies. Treatment of cancer cells and transgenic Pten knockout mice with Ch-319 downregulated PI3K/Akt signaling associated with elevation of FOXO3a expression. In addition, Ch-319 decreased expression of epithelial-mesenchymal transition markers N-cadherin and Vimentin with concomitant increase in E-cadherin in in vitro. Immunohistochemical examination of tumor sections also depicted reduction of proliferation markers. Moreover, evaluation of 78 compounds against Leishmania tropica kwh showed that 37, 5 and 1 organotin, indoline and ferrocene compounds, respectively inhibited growth of promastigotes. The selected 43 compounds predominantly organotin (IV) derivatives, halted the growth of Leishmania promastigotes partially by producing reactive oxygen species. Antileishmanial activity was reduced by 4.1-6.9 and 1.4-7.96% in triphenyltin (IV), 3.3-14.22 and 6.3-11.2% in tribenzyltin (IV), 5.2-34.38 and 1.8-38.2% in tributyltin (IV) and 7.9-15.7 and 5.2-15.4% in dibutyltin (IV) compounds in the presence of sodium azide and mannitol, respectively. Indolines and ferrocenes demonstrated antileishmanial activity reduction maximally in the presence of mannitol by 5.3 and 6.22%, respectively. Considering all these results, it is proposed that Ch-319 and Ch-620 have potential to be developed as anticancer agents against prostate cancer. Furthermore, organotin (IV) compounds in particular are also potent antileishmanial agents and detailed analysis on their mechanism is recommended.