Polysaccharides especially cellulose and pullulan are currently receiving much attention for industrial applications. Present study reports the synthesis, characterization and application of three succinate bonded polysaccharides, i.e., succinylated hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC) and pullulan. For macromolecular prodrug design, hydroxypropylcellulose-succinic anhydride (HPC-SAn) conjugate was synthesized by applying homogeneous conditions and HPC–SAn conjugate so formed was further attached to salicylic acid (SA) drug through covalent linkage by using ZrOCl2.8H2O as a catalyst for esterification. The resulting HPC-SAn-SA conjugate was subjected to multiple crosslinking using oxalyl chloride as cross-linking agent. The resultant cross-linked prodrug (CL-HPC-SAn-SA conjugate) was characterized using different spectroscopic techniques. UV/Vis analysis of the HPC-SAn-SA conjugate has indicated that it contains 26 mg of SA per 100 mg of CL-HPC-SAn-SA. CL-HPC-SAn-SA showed reasonably good swelling properties in water and at different physiological pH values (6.8 and 7.4). Kinetic studies revealed that CL-HPC-SAnSA followed second order swelling kinetics. Additionally, the CL-HPC-SAn-SA conjugate showed stimuli responsive (pH 7.4/1.2) swelling-deswelling properties. It was found by thermal analysis that CL-HPC-SAn-SA was thermally more stable compared to pure SA. These crosslinked prodrugs obtained after multiple crosslinking of drugs with polysaccharides may find their applications in the field of medicines and pharmaceutics. The second part of the study deals with the use of succinylated polysaccharides for metal sorption. For this purpose, Pull-Suc and HEC-Suc were synthesized applying homogeneous reaction by the esterification of pullulan and HEC with succinic anhydride in the presence of dimethyl amino pyridine (DMAP) as a catalyst. These conjugates were then converted into their sodic forms, i.e., Pull-Suc-Na and HEC-Suc-Na by alkaline treatment using saturated NaHCO3 solution. These novel sorbents were characterized using different spectroscopic techniques such as FT-IR, solidstate CP/MAS 13C NMR and thermal analysis. The Pull-Suc-Na and HEC-Suc-Na were then used for heavy metal removal from aqueous solution. The pHs corresponding to zero point charge of both sorbents were determined. A model study for the removal of Cd(II) from distilled water (DW) and spiked high-hardness groundwater (GW) by these chemically modified pullulan and HEC was conducted. Effect of contact time (5-120 min) and pH (2-8) on Cd-uptake by sorbents (Pull-Suc-Na and HEC-Suc-Na) was investigated. Sorption data was subjected to different kinetic and isotherm models but pseudo second order kinetic and Langmuir isotherm model provided the best fit to the experimental data. Maximum sorption capacities calculated by Langmuir model were found to be 476.2 mg g-1 from DW and 454.5 mg g-1 from GW by Pull-Suc-Na and 669.0 mg g-1 from DW and 630.0 mg g-1 from GW by HEC-Suc-Na. Such high values for removal of Cd(II) from GW suggest selectivity of these sorbents for removal of Cd in the presence of alkaline earth metal cation naturally presence in GW. Both the sorbents showed negligible decrease in Cd-uptake over five regeneration cycles suggesting their repeated use. Afterwards, both sorbents Pull-Suc-Na and HEC-Suc-Na were used to sorb Pb(II), Cr(VI), Co(III), Cu(II) and Ni(II) ions from aqueous solution by batch wise methodologies. The effects of initial metal concentration, sorbent dosage, contact time, pH and temperature were investigated. The data at optimized conditions was subjected to isotherm analyses. Langmuir isotherm and pseudo second order kinetic model provided the best fit to the experimental data of sorption of metal ions. Maximum sorption capacities of Pb(II), Cr(VI), Co(III), Cu(II) and Ni(II) from aqueous solution as calculated by Langmuir isotherm model were found to be 1000, 909.1, 625.0, 588.0 and 500.0 mg g-1, respectively by HEC-Suc-Na and 714.3, 588.2, 416.6, 357.1 and 250.0 mg g-1, respectively by Pull-Suc-Na. The negative values of ∆G° and ∆H° indicated spontaneity and exothermic nature of sorption. In order to simulate the real conditions, i.e., to prepare mediums containing heavy metal ions altogether, competitive sorption of these metal ions by the both sorbents was carried out. Results of competitive sorption reveal that the sorption capacities of Pb(II), Cr(VI), Cd(II), Ni(II) Co(VI) and Cu(VI) are in the order Pb(II) ˃ Cr(VI) ˃ Cd(II) ˃ Ni(II) ˃ Co(II) ˃ Cu(VI) for both HEC-Suc-Na and Pull-Suc-Na.
Pakistan’s involvement in the US war on terrorism was a tragic decision. No option was left for the ruling elite of Pakistan except to join the global war on terrorism and to take a U-turn from the support of Taliban’s regime in Afghanistan which was duly recognized by Pakistan’s government in 1996. It was expected by the policy-makers of the US that the alliance with Pakistan would provide extraordinary strength in combating the Al-Qaeda and other affiliated conglomerates in Afghanistan as well as in borderland area. However, after fifteen years of war, the alliance has enfeebled despite their mutual understanding regarding the objectives envisaged in the Strategic Partnership. The war on terrorism has now been escalated from Afghanistan to Pakistan and it has provided space to religious extremism, militancy, intolerance, ethnic division and sectarianism. There is no denial to the fact that religious extremism and terrorism are common threat and have damaged both the countries yet Pakistan has sacrificed more than the US in terms of human and material loss. Nevertheless, blame game and trust deficit is on the rise from both sides. This article focuses first on the joint ventures that the US and Pakistan mutually initiated to curb militant bloodbath in Afghanistan as well as in the border region. Secondly, it will explore factors responsible for increasing trust deficit between the partners. The study will not only provide deep understanding about the prevailing issues between Pakistan and the US but will also give true pictures to streamline the methodology for negotiating with each other in future.
Objective: to establish the safety and efficacy of hyoscine-N-butylbromide (Buscopan®) in accelerating labour in first time parturients.
Design: a randomised, double-blinded, placebo-controlled clinical trial.
Setting: the antenatal clinic and maternity unit of the Aga Khan University Hospital Nairobi, Kenya.
Population: first time parturients in spontaneous labour at term.
Methods: women were randomised to receive 40mg of hyoscine-N-butylbromide or sterile water for injection intravenously once they were confirmed to be in active labour. The dose could be repeated once after four hours.
Outcome measures: the main outcome measure was the duration of labour from diagnosis of active stage to delivery. Secondary outcome measures were rate of cervical dilatation and postpartum satisfaction score. Safety aspects such as drug adverse effects, APGAR scores and postpartum hemorrhage were explored.
Results: a total of 85 were randomised and 79 yielded data for analysis. Of these 37 received hyoscine-N-butylbromide and 42 received placebo. There was no significant difference in the mean duration of active labour to second stage between the drug and placebo arms (396.2 versus 389.3 minutes, respectively, p=0.881, 95% CI -85.9 to 99.8). The mean rate of cervical dilatation in the drug arm was 1.17 centimetres per hour (cm/hr) compared to 1.22cm/hr in the placebo arm. This difference was not statistically significant (p value=0.832, 95% CI -0.5 to 0.4). The postpartum satisfaction scores were similar between the two arms. Hyoscine-N-butylbromide was well tolerated without any major adverse effects observed in either arm.
Conclusion: hyoscine-N-butylbromide does not shorten the duration of labour in first time parturients in spontaneous labour. It also does not change maternal satisfaction with care received and is not associated with major adverse outcomes in the mother or newborn.