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Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. [ABSTRACT FROM AUTHOR]

For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Moscow and Islamabad have experienced many ups and downs throughout the past, but recent Russia Pakistan military and economic cooperation can be comprehended as significant progress in their relationship. As CPEC is a signatory sign of the Sino-Pak relationship, this paper seeks to analyze the need for Russia to be a part of CPEC as its inclusion in the project will also be significant for the regional integration and it will, even more, strengthen the relations of Beijing, Islamabad, and Moscow that will eventually build a new bloc. In addition, by giving the theoretical framework of complex interdependence theory, how Russia and Pakistan can work together in this project. Also, if Russia becomes a part of CPEC, how it can be helpful to eradicate all the apprehension which have been imposed by different entities to defame this project. [ABSTRACT FROM AUTHOR]

Carissa opaca (C.O) is a wild shrub, belonging to the family Apocynaceae. The medicinal virtues of this plant have long been known. The present study demonstrates the effects of aqueous-methanolic extract and various fractions (n-butanolic and aqueous) of Carissa opaca on cardiovascular parameters. The perfusion pressure (PP), force of contraction (FC) and heart rate (HR) were assessed on isolated heart of rabbit using Langendroff's technique for crude extract and fractions of C.O, followed by the elucidation of the mechanism of action after estimating toxicity of the plant. Negative ionotropic and positive chronotropic effects, with an increase in PP in isolated perfused rabbit heart were observed the with plant extract and fractions. The aqueous-methanolic extract exhibited maximum response at 1mg/ml while the n-butanolic and aqueous fractions showed a maximum response at 1mg/ml and 10μg/ml respectively. Both fractions produced the same response when treated with atropine (10-5 M), however the actions of adrenaline (10-5 M) and calcium chloride (10-5 M) remained unblocked. Acute toxicity studies indicated that the plant was safe up to 2000 mg/kg and sub-chronic studies demonstrated that no significant change in haematological and biochemical parameters observed. In conclusion, this study supports the folkloric claim of C.O extract. [ABSTRACT FROM AUTHOR]

This paper is an attempt to examine how is soft power and public diplomacy imperative conditions for Pakistan's international stature by examining the effective utilization of public diplomacy of the states like USA, Russia, China and India, public diplomacy of which have got a very significant position at the international stage. Based on an understanding of their Public diplomacy, the author seeks to explore what lessons and strategies should Pakistan take into consideration for the promotion of Pakistan's good image at the international front, and how Pakistan can be successful in achieving the positive results. The author has highlighted some serious recommendations as well. [ABSTRACT FROM AUTHOR]

The relations between Pakistan and Iran have been complex mix of cooperation and peer rivalry. The U.S has made struggle on various angles to convince Iran as a strategic partner to influence the relationship with this state in future. The United States influencing the Iran as a rich policy member in future while the Pakistan is the neighbor of Iran strategically and economically and a good ally of the United States in War on Terrorism. The U.S. drawdown from Afghanistan may lead to greater instability and a vacuum in that country. The Islamic Republic of Iran, one the most powerful regional actors in Afghanistan, is poised to exercise substantial influence there after the U.S. drawdown. In addition, the drawdown may provide Iran with the opportunity to strengthen ties with other powers involved in Afghanistan, such as India and Russia and Pakistan. This attendant scenario will more likely create an atmosphere of uncertainty in the region. This paper will explore the foreign Policy of Pakistan's towards Iran and the United States, is one of the influencing factors in this regard. [ABSTRACT FROM AUTHOR]

Moscow and Islamabad underwent a transition to say bye to past and develop a strong and stable relationship on mutual benefits. This paper analyses the factors related to both states building their relations in the perspective of geopolitical, geo-economics, regional and global changes. This piece also sheds light on the regional and global forces behind the closer linking and bringing of Moscow and Islamabad. The study finds that U.S/India strategic cooperation and the pangs of Afghanistan's unsteadiness play a crucial role in this regard. The discussion comes to the conclusion that strong relation of Russia with Pakistan does not mean a hostile relation with India as the later was the cornerstone of Moscow policy in South Asia and historical ally throughout the Cold War. The study also recommends that Moscow can play a vital role in easing the tension between the two rival states of South Asia through the Shanghai Cooperation Organization (SCO) and the Multi-polarity Movement. [ABSTRACT FROM AUTHOR]

China Pakistan Economic Corridor (CPEC) is considered being the Game Changer not only for Pakistan but also for the whole of South Asian region, Central Asia and Middle East. CPEC is the main component of Chinese One Belt One Road (OBOR) initiative that was designed to provide alternative communications trade routes to continue the economic growth rate of Beijing which was lasted for last three decades. Apart from its international posture, Beijing also dreamed to reduce the gap between Eastern and Western China to address the question of sovereignty, to ensure the control of central government in Western China, that was threatened by the Eastern Turkistan Islamic Movement (ETIMI) in Xinjiang province. Pakistan also has reposed high expectations in CPEC in terms of politics, economics, social and strategic that still dominate the national and foreign policy since its inception. Among them, Pakistan has a federal form of government that divide the powers between center and provinces which is guaranteed by the written constitution of Pakistan. Being a twoway traffic, federalism could not flourished smoothly and did not provide the actual and fair distribution of state power between the centers and federating units since the establishment of current constitution in 1973. This piece of work examines and analyses the contribution of CPEC to the addressing of issues that dominated federalism in Pakistan since 1947 and broke the state into two parts in 1971. It will also elaborate that CPEC will strengthen the system by providing equal share to the provinces in the billion dollars project or it will widen the gap by ignoring the small provinces in their legitimate rights. The study finds that unlike China, by analyzing the two years outcomes of CPEC, serious issues were raised from the small provinces. Additionally, the study come to the conclusion that if the central government could not take the issues and grievances of already War torn parts of Pakistan (KP, Baluchistan) and Sind, CPEC will lose its essence to make Pakistan in real terms a federal republic state, the one that is envisaged in the constitution. [ABSTRACT FROM AUTHOR]

Pakistan is encircled in different types of regional security threats. This paper focuses the threats to the security of Pakistan which emerged from Afghanistan with special focus on India. Long standing issues between India and Pakistan and anti-Pakistan activities of RAW and NDS in the context of their nexus for sponsoring terrorism created law and order situation in the country between 2000 and 2016. Moreover, the infiltration of terrorists into Pakistan, Indian water terrorism as well as subversive activities of different organisations are cause of concern for Islamabad. The increasing gap of Pakistan with its neighbouring countries except China has developed the possible isolation of Pakistan regionally. Regional environment is posing new challenges in the form of competition between regional countries which leads to hostility amongst them. [ABSTRACT FROM AUTHOR]

Indian percepts of China are biased by dread of Chinese hegemony; at present, many individuals in Indian security establishment has positioned China a greater menace than ever before. This paper investigates Sino-India relationship and Indian responses to Chinese ‘OBOR’ (One Belt, One Road) project by examining the extent and nature of their relationship within the diplomatic, geopolitical, economic, and defense spheres. There is power struggle between China and India for the dominance on Indian Ocean. The Indians perceive Chinese Maritime Silk Road projects as Indian encirclement with the development of ports projects in Indian Ocean, which are part of Chinese “String of Pearls” strategy. Chinese military naval ships and submarine presence in the number of ports around the Indian Ocean has made India anxious, the Indian policy experts perceive it as a threat to their national security and interest. From the Chinese perspective, ‘String of Pearls’ is a doctrine to free China from its Malacca dilemma. In Foreign Policy, the beginning of wisdom is to understand what the other party conceives, and why. And this is just as important for our Chinese friends as for the Indians. [ABSTRACT FROM AUTHOR]

Radicalization is a universal phenomenon with all its forms and manifestations encompassing entire spectrum of human behaviours and their resultant outcomes in different situations. Not as simplistic as it ostensibly seems, radicalization is a complex process as it can be manifested in various forms i.e. from non-violent to violent. The process of radicalization leading to violence follows a nonlinear, non-predetermined path, shaped by multiple factors--personal and collective, social and psychological. Due to multiple factors, Pakistan has been facing the menace of radicalization for long time especially after the US invasion in Afghanistan after 9/11 incident. Despite all efforts, Pakistan failed in deradicalization process. It is established fact that the divergent educational systems in Pakistan are one of the major reasons of radicalization. This paper focuses on how education can be used as remedial tool to get rid of the menace of radicalization. [ABSTRACT FROM AUTHOR]

The 2018 nuclear review of the United States would enhance arms race and provide greater leverage to battlefield of nuclear warheads while giving boost to application of tactical nuclear weapons, which historically NATO had inducted during the Cold War period against the former Soviet Union. Furthermore, American political and military leadership in its 2018 NPR has considered the dynamics of 'lowered nuclear threshold' which earlier in the 2010 Obama NPR revolved around 'increased nuclear threshold'. This happened due to undeclared Russian induction of tactical nuclear warheads in any possible war theatre with NATO at the European battlefield. Also, US acceptance of the lowered threshold would ignite a new wave of political orchestration around the globe particularly imposing political maneuvers against China and Russia including nations imposing strict protocols against US non-kinetic interventions. This research makes the point that possibility of war is possible under the new nuclear posture, which would be limited in scope and controlled in actions. Serious nations around the globe had already started non-kinetic war-gamming to evaluate the US doctrine and how it helps Washington to politically craft the environment in the regions such as South East Asia, South Asia, Middle East, and states compiling pro-Russian Eastern Europe. The findings of this study are based on deductive approach with hypothetical premises mentioned above. [ABSTRACT FROM AUTHOR]

The relations between Pakistan and Iran, dates back to the early stages of Pakistan independence in 1947. These two neighbours in the South Asia exploited their natural resources and location in Indian Ocean Region to foster unity in the region and sub-region, essentially for the attainment of their national interests. However, convergence and divergence of interests affected the cordial relations between Pakistan and Iran. These concerns were broadly categorized as economic, political security/defence imperatives. The changing international environment where a nation's geographical boundary was no longer a restriction to international trade has necessitated the need for Pakistan and Iran to improve their relations in order to benefit from the international system. Therefore, the way-forward on Pakistan-Iran relations would entail a conscientious effort by both nations to tackle these concerns. [ABSTRACT FROM AUTHOR]

The cardiovascular activity of aqueous methanolic extract of Paspalidium flavidum L. was evaluated on isolated rabbit heart and aorta. Heart rates, force of contraction and perfusion pressure were assessed in the presence of different concentrations of extract and adrenaline by using Langendorff's technique. Moreover, the vasoconstriction effects were studied in rabbit aorta using isolated organ bath. The results indicated that the extract (lng-lOOug/ml) exhibited a significant increase in heart rate, contractility and perfusion pressure of isolated rabbit's heart; with a maximum effect at 1ng/ml, which was comparable to adrenaline (1µg/ml). Similarly, adrenaline at doses from 1-10µg/ml produced a significant dose dependant increase in all the cardiac parameters. The cardiotonic effects of the extract were significantly blocked by propranolol (10-5M) while an increase in perfusion pressure was completely antagonized by verapamil (10-6M). Activity of cardiac marker enzymes was also significantly raised in the perfusate of isolated heart pretreated with the extract. In rabbit aorta, the extract exhibited a dose dependent vasoconstriction effect however it did not increase the tone of aorta when pre-treated with verapamil (10-6M). It is conceivable therefore; that the cardiotonic and vasoconstriction effects of the extract might be due to its agonistic actions on β-receptors and Ca+2 channels. [ABSTRACT FROM AUTHOR]