Page 3-13 Efficient Synthesis of Functionalized Dibenzothiophenes by Domino ′ ′ ′ ′Twofold Heck /... more Page 3-13 Efficient Synthesis of Functionalized Dibenzothiophenes by Domino ′ ′ ′ ′Twofold Heck / 6π π π π-Electrocyclization′ ′ ′ ′ Reactions of 2, 3-Dibromobenzothiophene and 2,3,6-Tribromobenzothiophene The palladium(0)-catalyzed Heck crosscoupling reactions of di-and tribromobenzothiophene provided functionalized dibenzothiophene by a domino ′twofold Heck / 6π-electrocyclization. The products were transformed by Pd/C-catalyzed oxidation to the corresponding dibenzothiophenes.
Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ ... more Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ gels) containing Saussurea lappa root extract (SLRE) via excision wound induction in albino rats. Methods: Preliminary phytochemical analysis of the methanol extract of roots of Saussurea lappa (SLRE) was performed using standard procedures. In vitro anti-inflammatory assay of SLRE was conducted using heat-induced hemolysis method at a concentration of 100 μg/mL. Acute toxicity of SLRE was also evaluated in mice at a single dose of 1000 mg/kg for 24 h. Emulgels and in situ gels were prepared using different concentrations of SLRE and assessed for their organoleptic and physical properties. In vitro drug release studies of the prepared formulations were carried out by Franz diffusion cell and the data fitted into various pharmacokinetic models. Wound healing was assessed using excision wound induction (380 mm2) on dorsal surface of male albino rats. Each formulation (F4, F5, F6, G1, G2...
Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countr... more Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countries. It is characterized by permanent or transient cerebral ischemia and it activates syndrome of pathological events such as membrane depolarization, glutamate excitotoxicity, and intracellular calcium buildup. Carveol is widely employed as anti-inflammatory and antioxidant in traditional Chinese medicine. In the present study, the neuroprotective effects of post-treated carveol were demonstrated against transient middle cerebral artery occlusion (MCAO) induced focal ischemic cerebral injury. Male Sprague Dawley (SD) rats were subjected to two different experimental protocols to determine the dose and effects of carveol, and to demonstrate the underlying role of the nuclear factor E2-related factor (Nrf2) pathway. Our results showed that MCAO induced marked neuronal injury in the ipsilateral cortex and striatum associated with higher inflammatory cytokines expression, along with apoptotic markers such as caspase-3 and the phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, MCAO induced a marked increase in oxidative stress as evidenced by high lipid peroxidase (LPO) content accompanied by the depressed antioxidant system. Carveol significantly reversed the oxidative stress and downregulated inflammatory cascades by enhancing endogenous antioxidant mechanisms including the Nrf2 gene, which critically regulates the expression of several downstream antioxidants. Further, to determine the possible involvement of Nrf2 in carveol mediated neuroprotection, we antagonized Nrf2 by alltrans retinoic acid (ATRA), and such treatment abrogated the protective effects of carveol accompanied with exaggerated neuronal toxicity as demonstrated by higher infarction area. The target effects of carveol were further supported by molecular docking analysis of drug-protein interactions. Together, our findings suggest that carveol could activate endogenous master anti-oxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating MCAO-induced neuroinflammation and neurodegeneration.
China-Pakistan Economic Corridor (CPEC) is an important topic of debate in the economic circles n... more China-Pakistan Economic Corridor (CPEC) is an important topic of debate in the economic circles nowadays. The project is expected to result in huge investments in Pakistan, but whether it will result in uplift of its economy is uncertain keeping in view the outcome of such ventures in the past. This study investigates the impact of Foreign Direct Investment (FDI) and External Debt (ED) on the Economic Growth (EG) of Pakistan by using larger sample size that spans from 1970-2015. Besides the two explanatory variables (FDI & ED), three control variables (Repayments of External Debt, Net Official Development Assistance, and Exchange Rate) are included in the research model. The empirical analysis is conducted using Auto Regressive Distributed Lag (ARDL) model while Bounds test approach of co-integration is used to test the long run impact of these variables. The findings of this research highlights that FDI inflow in Pakistan has insignificant impact on its EG in the long run, however in the short run it has a significant and positive effect. Furthermore, no impact of ED on EG is observed in the long run, but a negative impact in the short run is noticed. This may imply that considerable attention is required to make this project a success.
Journal of the College of Physicians and Surgeons Pakistan Jcpsp, Dec 1, 2009
Objective: To determine the outcome of treatment in terms of infection and recurrence using open ... more Objective: To determine the outcome of treatment in terms of infection and recurrence using open extraperitoneal mesh repair technique.
A preterm neonate presenting with respiratory distress after birth was found to have a clival enc... more A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion.
A series of mono-, di-and tri-nuclear Ni(II) complexes of N, O-donating molecules possessing AH 2... more A series of mono-, di-and tri-nuclear Ni(II) complexes of N, O-donating molecules possessing AH 2 CANHA and AHC@NA moieties have been synthesized and characterized and the structures have been determined by single crystal X-ray diffraction. All these exhibited interesting molecular packing in their crystal lattices. Di-nuclear complexes were found to be cleaved in pyridine to result in mononuclear ones with additional coordinations being provided by pyridine. Di-nuclear complexes were found to form urea adducts as demonstrated based on absorption and vibrational studies.
Introduction. In recent years, site-selective reactions of polyhalogenated hetero-cycles have b... more Introduction. In recent years, site-selective reactions of polyhalogenated hetero-cycles have been intensively studied [1][2]. Cross-coupling reactions of 2,5-dibromo-pyridine include aminations [3], and Stille [4], Suzuki [5], Negishi [6], Sonogashira [7], and Kumada couplings [8]. In all ...
Floodwaters differ markedly in dissolved CO2, yet the effects of CO2 on submergence responses of ... more Floodwaters differ markedly in dissolved CO2, yet the effects of CO2 on submergence responses of terrestrial plants have rarely been examined. The influence of dissolved CO2 on underwater photosynthesis and growth was evaluated for three accessions of the wetland plant Hordeum marinum Huds. All three accessions tolerated complete submergence, but only when in CO2 enriched floodwater. Plants submerged for 7 days in water at air equilibrium (18 µM CO2) suffered loss of biomass, whereas those with 200 µM CO2 continued to grow. Higher underwater net photosynthesis at 200 µM CO2 increased by 2.7- to 3.2-fold sugar concentrations in roots of submerged plants, compared with at air equilibrium CO2. Leaf gas films enhancing gas exchange with floodwater, lack of a shoot elongation response conserving tissue sugars and high tissue porosity (24–31% in roots) facilitating internal O2 movement, would all contribute to submergence tolerance in H. marinum. The present study demonstrates that dissol...
Suzuki-Miyaura reactions of the bis(triflate) of 5,7-and 7,8dihydroxyflavone proceed with very go... more Suzuki-Miyaura reactions of the bis(triflate) of 5,7-and 7,8dihydroxyflavone proceed with very good site selectivity in favor of position 7 and allow the synthesis of various arylated flavones. The reaction of 5,7-dihydroxyflavone with one equivalent of triflic anhydride also proceeds with very good
Objective: To assess the local wound complications in complicated/ high risk laparotomies in term... more Objective: To assess the local wound complications in complicated/ high risk laparotomies in terms of wound dehiscence and incisional hernia formation with a modified technique of midline abdominal wound closure.
Polyhalogenated molecules represent interesting substrates in palladium(0)-catalyzed cross-coupli... more Polyhalogenated molecules represent interesting substrates in palladium(0)-catalyzed cross-coupling reactions. [4] Recently, we have reported Suzuki-Miyaura and Heck reactions of tetrabromothiophene, tetrabromo-N-methylpyrrole, tetrabromoselenophene, and other ...
A new born baby boy presented with birth asphyxia and respiratory distress. He went into cardiac ... more A new born baby boy presented with birth asphyxia and respiratory distress. He went into cardiac arrest twice but was resuscitated. On detailed evaluation, he had low set ears and micrognathia with glossoptosis consistent with features of Pierre Robin sequence. ...
A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedu... more A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedure is based on the one-pot oxidative decarboxylation−β-iodination of α-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different ...
Objectives: Infectious diseases that are largely treatable continue to pose a tremendous burden o... more Objectives: Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. Methods: In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. Results: We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. Conclusions: We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health. Recent progress in the availability of highly efficacious therapeutic drugs has made it possible to lessen the infectious disease burden in the developing world. However, lack of diagnostics in resource-limited settings remains a major obstacle to treating such diseases. Reliable diagnostics are required not only for identifying patients in need of the relevant therapy but also for avoiding overtreatment or mistreatment, which often leads to drug resistance. Despite revolutionary advances in this field, almost all diagnostic tools remain largely inaccessible to developing countries. There is a notorious gap (referred to as the "10/90" gap) between the latter and industrialized countries, whereby 90% of the research money in genomics and related biotechnologies is focused on the health needs of only 10% of the world's population. 1 Current state-of-the-art laboratory medicine is highly dependent on complex platforms that assume advanced infrastructure, Upon completion of this activity you will be able to: • describe the impact of accessible molecular diagnostics in the developing world. • define the characteristics of accessible molecular diagnostics. • list the challenges of accessible test development. • discuss test modifications needed for democratizing polymerase chain reaction-based molecular diagnostics. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.
Page 3-13 Efficient Synthesis of Functionalized Dibenzothiophenes by Domino ′ ′ ′ ′Twofold Heck /... more Page 3-13 Efficient Synthesis of Functionalized Dibenzothiophenes by Domino ′ ′ ′ ′Twofold Heck / 6π π π π-Electrocyclization′ ′ ′ ′ Reactions of 2, 3-Dibromobenzothiophene and 2,3,6-Tribromobenzothiophene The palladium(0)-catalyzed Heck crosscoupling reactions of di-and tribromobenzothiophene provided functionalized dibenzothiophene by a domino ′twofold Heck / 6π-electrocyclization. The products were transformed by Pd/C-catalyzed oxidation to the corresponding dibenzothiophenes.
Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ ... more Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ gels) containing Saussurea lappa root extract (SLRE) via excision wound induction in albino rats. Methods: Preliminary phytochemical analysis of the methanol extract of roots of Saussurea lappa (SLRE) was performed using standard procedures. In vitro anti-inflammatory assay of SLRE was conducted using heat-induced hemolysis method at a concentration of 100 μg/mL. Acute toxicity of SLRE was also evaluated in mice at a single dose of 1000 mg/kg for 24 h. Emulgels and in situ gels were prepared using different concentrations of SLRE and assessed for their organoleptic and physical properties. In vitro drug release studies of the prepared formulations were carried out by Franz diffusion cell and the data fitted into various pharmacokinetic models. Wound healing was assessed using excision wound induction (380 mm2) on dorsal surface of male albino rats. Each formulation (F4, F5, F6, G1, G2...
Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countr... more Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countries. It is characterized by permanent or transient cerebral ischemia and it activates syndrome of pathological events such as membrane depolarization, glutamate excitotoxicity, and intracellular calcium buildup. Carveol is widely employed as anti-inflammatory and antioxidant in traditional Chinese medicine. In the present study, the neuroprotective effects of post-treated carveol were demonstrated against transient middle cerebral artery occlusion (MCAO) induced focal ischemic cerebral injury. Male Sprague Dawley (SD) rats were subjected to two different experimental protocols to determine the dose and effects of carveol, and to demonstrate the underlying role of the nuclear factor E2-related factor (Nrf2) pathway. Our results showed that MCAO induced marked neuronal injury in the ipsilateral cortex and striatum associated with higher inflammatory cytokines expression, along with apoptotic markers such as caspase-3 and the phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, MCAO induced a marked increase in oxidative stress as evidenced by high lipid peroxidase (LPO) content accompanied by the depressed antioxidant system. Carveol significantly reversed the oxidative stress and downregulated inflammatory cascades by enhancing endogenous antioxidant mechanisms including the Nrf2 gene, which critically regulates the expression of several downstream antioxidants. Further, to determine the possible involvement of Nrf2 in carveol mediated neuroprotection, we antagonized Nrf2 by alltrans retinoic acid (ATRA), and such treatment abrogated the protective effects of carveol accompanied with exaggerated neuronal toxicity as demonstrated by higher infarction area. The target effects of carveol were further supported by molecular docking analysis of drug-protein interactions. Together, our findings suggest that carveol could activate endogenous master anti-oxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating MCAO-induced neuroinflammation and neurodegeneration.
China-Pakistan Economic Corridor (CPEC) is an important topic of debate in the economic circles n... more China-Pakistan Economic Corridor (CPEC) is an important topic of debate in the economic circles nowadays. The project is expected to result in huge investments in Pakistan, but whether it will result in uplift of its economy is uncertain keeping in view the outcome of such ventures in the past. This study investigates the impact of Foreign Direct Investment (FDI) and External Debt (ED) on the Economic Growth (EG) of Pakistan by using larger sample size that spans from 1970-2015. Besides the two explanatory variables (FDI & ED), three control variables (Repayments of External Debt, Net Official Development Assistance, and Exchange Rate) are included in the research model. The empirical analysis is conducted using Auto Regressive Distributed Lag (ARDL) model while Bounds test approach of co-integration is used to test the long run impact of these variables. The findings of this research highlights that FDI inflow in Pakistan has insignificant impact on its EG in the long run, however in the short run it has a significant and positive effect. Furthermore, no impact of ED on EG is observed in the long run, but a negative impact in the short run is noticed. This may imply that considerable attention is required to make this project a success.
Journal of the College of Physicians and Surgeons Pakistan Jcpsp, Dec 1, 2009
Objective: To determine the outcome of treatment in terms of infection and recurrence using open ... more Objective: To determine the outcome of treatment in terms of infection and recurrence using open extraperitoneal mesh repair technique.
A preterm neonate presenting with respiratory distress after birth was found to have a clival enc... more A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion.
A series of mono-, di-and tri-nuclear Ni(II) complexes of N, O-donating molecules possessing AH 2... more A series of mono-, di-and tri-nuclear Ni(II) complexes of N, O-donating molecules possessing AH 2 CANHA and AHC@NA moieties have been synthesized and characterized and the structures have been determined by single crystal X-ray diffraction. All these exhibited interesting molecular packing in their crystal lattices. Di-nuclear complexes were found to be cleaved in pyridine to result in mononuclear ones with additional coordinations being provided by pyridine. Di-nuclear complexes were found to form urea adducts as demonstrated based on absorption and vibrational studies.
Introduction. In recent years, site-selective reactions of polyhalogenated hetero-cycles have b... more Introduction. In recent years, site-selective reactions of polyhalogenated hetero-cycles have been intensively studied [1][2]. Cross-coupling reactions of 2,5-dibromo-pyridine include aminations [3], and Stille [4], Suzuki [5], Negishi [6], Sonogashira [7], and Kumada couplings [8]. In all ...
Floodwaters differ markedly in dissolved CO2, yet the effects of CO2 on submergence responses of ... more Floodwaters differ markedly in dissolved CO2, yet the effects of CO2 on submergence responses of terrestrial plants have rarely been examined. The influence of dissolved CO2 on underwater photosynthesis and growth was evaluated for three accessions of the wetland plant Hordeum marinum Huds. All three accessions tolerated complete submergence, but only when in CO2 enriched floodwater. Plants submerged for 7 days in water at air equilibrium (18 µM CO2) suffered loss of biomass, whereas those with 200 µM CO2 continued to grow. Higher underwater net photosynthesis at 200 µM CO2 increased by 2.7- to 3.2-fold sugar concentrations in roots of submerged plants, compared with at air equilibrium CO2. Leaf gas films enhancing gas exchange with floodwater, lack of a shoot elongation response conserving tissue sugars and high tissue porosity (24–31% in roots) facilitating internal O2 movement, would all contribute to submergence tolerance in H. marinum. The present study demonstrates that dissol...
Suzuki-Miyaura reactions of the bis(triflate) of 5,7-and 7,8dihydroxyflavone proceed with very go... more Suzuki-Miyaura reactions of the bis(triflate) of 5,7-and 7,8dihydroxyflavone proceed with very good site selectivity in favor of position 7 and allow the synthesis of various arylated flavones. The reaction of 5,7-dihydroxyflavone with one equivalent of triflic anhydride also proceeds with very good
Objective: To assess the local wound complications in complicated/ high risk laparotomies in term... more Objective: To assess the local wound complications in complicated/ high risk laparotomies in terms of wound dehiscence and incisional hernia formation with a modified technique of midline abdominal wound closure.
Polyhalogenated molecules represent interesting substrates in palladium(0)-catalyzed cross-coupli... more Polyhalogenated molecules represent interesting substrates in palladium(0)-catalyzed cross-coupling reactions. [4] Recently, we have reported Suzuki-Miyaura and Heck reactions of tetrabromothiophene, tetrabromo-N-methylpyrrole, tetrabromoselenophene, and other ...
A new born baby boy presented with birth asphyxia and respiratory distress. He went into cardiac ... more A new born baby boy presented with birth asphyxia and respiratory distress. He went into cardiac arrest twice but was resuscitated. On detailed evaluation, he had low set ears and micrognathia with glossoptosis consistent with features of Pierre Robin sequence. ...
A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedu... more A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedure is based on the one-pot oxidative decarboxylation−β-iodination of α-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different ...
Objectives: Infectious diseases that are largely treatable continue to pose a tremendous burden o... more Objectives: Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. Methods: In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. Results: We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. Conclusions: We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health. Recent progress in the availability of highly efficacious therapeutic drugs has made it possible to lessen the infectious disease burden in the developing world. However, lack of diagnostics in resource-limited settings remains a major obstacle to treating such diseases. Reliable diagnostics are required not only for identifying patients in need of the relevant therapy but also for avoiding overtreatment or mistreatment, which often leads to drug resistance. Despite revolutionary advances in this field, almost all diagnostic tools remain largely inaccessible to developing countries. There is a notorious gap (referred to as the "10/90" gap) between the latter and industrialized countries, whereby 90% of the research money in genomics and related biotechnologies is focused on the health needs of only 10% of the world's population. 1 Current state-of-the-art laboratory medicine is highly dependent on complex platforms that assume advanced infrastructure, Upon completion of this activity you will be able to: • describe the impact of accessible molecular diagnostics in the developing world. • define the characteristics of accessible molecular diagnostics. • list the challenges of accessible test development. • discuss test modifications needed for democratizing polymerase chain reaction-based molecular diagnostics. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.
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Papers by Imran Malik