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Entrepreneurship is crucial for alleviating job challenges among business graduates and for sustaining a growing local economy. However, different factors support and encourage students to be entrepreneurs. Modern technologies such as social media are becoming more popular with young people in enterprise creation. However, the connection between social media use and business among the youth of developing countries has yet to be noticed. This study examines the relationship between entrepreneurial education (EE), attitudes toward sustainable entrepreneurship (ATSE), and sustainable entrepreneurial intentions (SEIs); as well as examining the moderating effect of social media adoption on this relationship. To put the proposed concept to the test, data was collected from 314 business graduates from Pakistani universities. Structural equation modeling using AMOS (Version 26) was utilized to test the proposed hypotheses. The study findings show that student attitudes concerning sustainable entrepreneurship mediate the association between EE and sustainable entrepreneurial intention. Furthermore, the results illustrate that social media moderated the relationship between the research participants’ attitudes concerning sustainable entrepreneurship and their desire to practice sustainable entrepreneurship. The study makes significant contributions to the field that scholars can use to initiate future research projects.

Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic agents such as platinum-based compounds are frequently used single-handedly or accompanied by additional chemotherapies to treat cancer patients. Chemotherapy-induced peripheral painful neuropathy is seen in around 40% of patients who are treated with platinum-based compounds, including cisplatin. This not only decreases the quality of life of patients but also patients’ compliance with cisplatin. Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain, coupled with cisplatin in cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed the same strategy to induce tolerance in mice. Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot plate test, tail-flick tests and von Frey filament in mouse models. Furthermore, we investigated the effects of BNZ on the expression of Tumor Necrosis Factor-alpha (TNF-α) in the spinal cord. Results: The results showed that BNZ reduced tolerance to analgesic effects of nalbuphine and TNF-α expression in mice. Conclusion: BNZ could be a potential drug candidate for the management of nalbuphine-induced tolerance in cisplatin-induced neuropathic pain.

The paper investigates the impact of energy investment on economic growth for Pakistan using Solow model. The energy is introduced as factor input in the Solow growth model along with physical capital, labor and human capital and some other policy variables. The period of analysis ranges from 1970 to 2018. The Autoregressive Distributed Lag (ARDL) approach confirms that energy investment contributes positively to economic growth both in the short and the long run along with trade openness. The study provides an important policy recommendation that government should encourage the investment activities in energy sector to meet the rising energy demand which in turn stimulates economic growth.Keywords: Energy Investments, Economic Growth, ARDL.JEL Classifications: O47, O13, Q43DOI: https://doi.org/10.32479/ijeep.9704

Introduction Physical, chemical, thermal injuries along with infectious diseases lead to acute pain with associated inflammation, being the primary cause of hospital visits. Moreover, neuropathic pain associated with diabetes is a serious chronic disease leading to high morbidity and poor quality of life. Objective Earlier multiple sulphonamides have been reported to have an antinociceptive and antiallodynic profile. 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS), a synthetic sulfonamide with reported carbonic anhydrase inhibitory activity, was investigated for its potential effects in mice model of acute and diabetic neuropathic pain. Methods and results 4-FBS was given orally (p.o.) one hour before the test and then mice were screened for antinociceptive activity by using the tail immersion test, which showed significant antinociceptive effect at both 20 and 40 mg/kg doses. To explore the possible mechanisms, thermal analgesia of 4-FBS was reversed by the 5HT3 antagonist ondansetron 1mg/kg intraperitoneally (i.p.) and by the µ receptor antagonist naloxone (1 mg/kg i.p.), implying possible involvement of serotonergic and opioidergic pathways in the analgesic effect of 4-FBS. Diabetes was induced in mice by a single dose of streptozotocin (STZ) 200 mg/kg i.p. After two weeks, animals first became hyperalgesic and progressively allodynic in the fourth week, which was evaluated through behavioral parameters like thermal and mechanical tests. 4-FBS at 20 and 40 mg/kg p.o. significantly reversed diabetes-induced hyperalgesia and allodynia at 30, 60, 90, and 120 minutes. Conclusion These findings are significant and promising while further studies are warranted to explore the exact molecular mechanism and the potential of 4-FBS in diabetic neuropathic pain.

Naeem Ur Rehman,1 Muzaffar Abbas,2 Mariya al-Rashida,3 Ahmed Tokhi,1 Muhammad Awais Arshid,4 Muhammad Sona Khan,1 Izhar Ahmad,1 Khalid Rauf1 1Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Islamabad, Pakistan; 2Department of Pharmacy, Capital University of Science and Technology (CUST), Islamabad, Pakistan; 3Department of Chemistry, Forman Christian College (A Chartered University), Lahore 54600, Pakistan; 4Aga Khan University, Karachi, PakistanCorrespondence: Khalid Rauf Tel +92 345 9824468Email khalidrauf@cuiatd.edu.pkIntroduction: Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release.Objective: The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization.Methods: In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV.Results: Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum.Conclusion: The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS.Keywords: 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS), nicotine sensitization, pharmacotherapy, drug addiction, locomotor activity, adenosine, HPLC

Frankincense (This inclusive review focuses on the significance of frankincense diterpenoids, and in particular, incensole derivatives for establishment future treatments of depression, neurological disorders, and cancer. The authors survey the available literature and furnish an overview of future perspectives of these intriguing molecules.Numerous diterpenoids including cembrane, prenylaromadendrane, and the verticillane-type have been isolated from various

Routinely used anti-inflammatory drugs are associated with off-target effects such as cyclooxygenase (COX)-1 inhibition and gastric ulcers. The aim of this study is to examine the anti-inflammatory potential and gastroprotective effects of synthetic amino acid derivatives of 2-mercaptobenzimidazole (MBAA1, MBAA2, MBAA3, MBAA4 and MBAA5). The results showed that compound MBAA5 possess a potential anti-inflammatory action by inhibition of 15-LOX and COX-2. MBAA5 also attenuated the pro-inflammatory cytokines and mediators (TNF-α, IL-1β and COX-2) in rat hind paw in carrageenan-induced inflammatory model of rat. 2-mercaptobenzimidazole derivative, MBAA5 also inhibited gastric H+/K+ ATPase and demonstrated a better selectivity index for COX-2 (SI 27.17) in comparison to celecoxib (SI 41.43). Molecular docking studies predicted the binding interactions of the synthesized compounds with retrieved target proteins of H

BACKGROUND: Previous studies have shown that α7 nicotinic acetylcholine receptor (nAChR) has a critical role in the regulation of pain sensitivity and neuroinflammation. However, pharmacological effects of α7 nAChR activation in the hippocampus on neuroinflammatory mechanisms associated with allodynia and hyperalgesia remain unknown. We have determined the effects of 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an α7 nAChR positive allosteric modulator, on lipopolysaccharide (LPS)-induced allodynia and hyperalgesia in mice. We also evaluated the effects of TQS on immunoreactivity of microglial marker ionized-calcium binding adaptor molecule 1 (Iba-1), phospho-nuclear factor-κB (p-NF-κB p(65)), tumor necrosis factor-alpha (TNF-α), and norepinephrine (NE) level. METHODS: Mice were treated with (0.25, 1 or 4 mg/kg, ip) followed by LPS (1 mg/kg, ip) administration. Allodynia and hyperalgesia were determined using von Frey filaments and hot plate respectively. Immunoreactivity of Iba-1, p-NF-κB p(65), and TNF-α, were measured in the hippocampus using immunofluorescence assay. Hippocampal NE level was evaluated using high performance liquid chromatography. RESULTS: LPS administration resulted in allodynia and hyperalgesia in mice after six h. Systemic administration of TQS prevented LPS-induced allodynia and hyperalgesia. TQS pretreatment significantly decreased the immunoreactivity of Iba-1, p-NF-κB, and TNF-α in CA1 and DG regions of the hippocampus. In addition, TQS reversed LPS-induced NE reduction in the hippocampus. CONCLUSIONS: Taken together, our results suggest that TQS prevented LPS-induced allodynia and hyperalgesia, upregulation of TNF-α expression and NE level reduction involving microglial α7 nAChR in part in the hippocampus. Therefore, these findings highlight the important effects of α7 nAChR allosteric modulator against symptoms of inflammatory pain.

The purpose of the article: This research explored and contributes to the leadership literature by investigating the influence of transactional leadership over employee engagement at certain banks located in KPK and Punjab province of Pakistan. It observes the influence of main aspects i-e contingent reward, active management by exception (MBE active) on worker’s regular job commitmentMaterials and methods: This distinctive combination of leadership behaviors are compared with attention given specifically to everyday work settings. Twenty banks are selected involving 180 employees. Questionnaires and interviews are conducted to collect data.Results of the research: The relationships among variables are examined through the Spearman Rank-order correlation coefficient. The moderating effects associated with corporate culture are observed by employing multiple regression analyses. A positive and significant relationship is revealed between transactional management and chosen variables except “passive management by exemption”. It is safely predicted that employee job satisfaction can be greatly elevated through transactional leadership. It is established that “contingent reward” and “active management by exemption” improve worker's engagement in contrast to passive management by exemption. Applications: This research can be used for universities, teachers, and students. Novelty/Originality: In this research, the model of Drivers of Employee Engagement and Role of Transactional Leadership-Case of Pakistani Banking Sector is presented in a comprehensive and complete manner.

Zulkifal Malik,1,2 Muzaffar Abbas,2 Lina Tariq Al Kury,3 Fawad Ali Shah,1 Mahboob Alam,2 Arif-ullah Khan,1 Humaira Nadeem,1 Saad Alghamdi,4 Muhammad Umar Khayam Sahibzada,5 Shupeng Li6 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 2Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan; 3College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates; 4Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan; 6State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaCorrespondence: Muzaffar AbbasFaculty of Pharmacy, Capital University of Science and Technology, Islamabad Expressway, Kahuta Road, Zone-V, Islamabad, PakistanTel +92-51-111555666Fax +92-51-4486705Email Muzaffar.abbas@cust.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Shenzhen, 518055, People’s Republic of ChinaEmail lisp@pku.edu.cnBackground: Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice.Methods: The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression was measured by enzyme-linked immunosorbent assay. Acute and sub-acute toxicity studies were conducted to evaluate the toxicity profile of compounds.Results: Treatment with the thiazolidine derivative, 1b and 1d, attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg. No motor coordination deficits were observed in animals. The compounds also reduced IL-1β expression in the spinal cord of mice. Acute and sub-acute toxicity studies revealed that both compounds were safe.Conclusion: The compounds exhibit promising activity against inflammatory pain due to their ability to produce anti-hyperalgesic and anti-allodynic effects and to inhibit IL-1β expression in the spinal cord.Keywords: inflammatory pain, IL-1β, thiazolidine derivatives, mechanical allodynia, thermal hyperalgesia

The Water and Sanitation Agency (WASA) of Lahore, Pakistan, supplies water to 5.29 million people through 598 tube wells but faces difficulties in meeting rapidly increasing water demand, lowering groundwater table, high energy costs, and low water tariffs. However, the actual water consumption and water loss have never been estimated due to water meter outages. This study aimed to estimate the actual water consumption, production, and water losses for the WASA Lahore service area, using the limited number of working water meters and pump operation data. The actual water consumption was estimated by 14,030 working customer meters; the population census was 44.02 m3 per connection per month, or 200 L per capita per day, while the water production was 79.8 m3 per connection. The actual water loss was significantly higher than non-revenue water, with an average of 45.4% (ranging from 35.9–69.4%). Due to high electricity costs, WASA has had to cut their supply hours. Therefore, leakage reduction programs must be implemented in the high-water-loss townships found in this study in order to meet the increasing water demand, reduce electricity consumption, and alleviate groundwater table drawdown.

The expectancy of life has been increasing in the Western world since long time due to optimal standards of life, good hygienic conditions, and, of course, advancement in modern medicine. The current chapter provides a brief overview of nanotechnology-based treatment approaches for skin cancer. Unique physicochemical characteristics and biomedical advancement for the development of nanocarriers have provided applications in targeting drug delivery, diagnosis, and patient compliance. Doxorubicin (DOX) biodegradable and biocompatible nanocarrier systems have shown enhanced bioavailability, therapeutic index, and thus, reduced treatment costs. For instance, the date of doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) particles serves as translational link for clinical trials assessing anticancer efficacy and diagnostic potential, via DOX optical imaging of formulation after appropriate testing and guidance for further studies, leading to clinical evaluation to determine safety margins of formulation.

Social Media (SM) is considered one of the most discussed topics in today&rsquo, s business environment, mostly because of the recent developments and improvements in computer and ICT (Information and Communications Technology) technologies. However, very little is known about Social Media&rsquo, s (SM) role in creating Small and Medium-sized Enterprises&rsquo, (SMEs&rsquo, ) financial sustainability. Drawing upon the Technology Organisational and Environmental (TOE) framework, the authors constructed a comprehensive model that examined the role of different factors in the adoption of SM by SMEs in developing countries (using Pakistan as an example). Using a questionnaire survey of 383 owners/managers of SMEs in Pakistan, the research findings determined the different factors (i.e., organisational, technological, and environmental), which can impact the adoption of SM by SMEs. In line with previous research studies, the results of structural equation modelling show that technological factors such as perceived benefits of SM, compatibility of SM, cost, and trust have a substantial effect on SMEs&rsquo, SM adoption. Similarly, both organisational factors: top management support and technological competence, are strong predictors of SM adoption in SMEs. Finally, environmental factors (i.e., competitor pressure, customer pressure, and information intensity) positively impacted SM adoption by SMEs. The effect of SM adoption on SMEs&rsquo, financial sustainability was also tested and found to be positive and significant. Several theoretical and practical implications for owners/managers and other stakeholders regarding SM&rsquo, s successful implementation by SMEs are highlighted within the paper.

Organizations in the current competitive and challenging situation considered organizational process innovation to sustain themselves with competitive advantage and provisioning of high value products to consumers. The current study investigates the role of transformational leadership traits and knowledge management practices on predicting the process innovation in FMCG companies. Data has been collected from the 10 FMCG companies located in major two cities i.e. Lahore and Karachi, Pakistan. Sample of 200 top line managers have been selected by convenience sampling method and adapted itemized questionnaire has been presented to the top management after a brief session of face to face interviews. Response of 170 top line employees has been registered and statistical testing has been done on SPSS 22. Results indicated that the transformational leadership traits has significantly positive impact on process innovation which effectively expedites the production efficiency of manufacturing units. The knowledge management practices such as acquisition, transfer and application has strong and positively significant association with process innovation. The knowledge management practices positively mediates with transformational leadership traits and resultantly lays foundation for continuous process improvement to survive in market. This conceptual model practically helps the production and manufacturing companies to nurture positive change management attitudes, decreasing production time, expanding products range, development of skills needed to advocate and adopt change, employee involvement, commitment and benefits of large scale economy. This study is limited to FMCGs in major cities and can be expanded to services industry and test the conceptual model.

Carbonic anhydrase (CA) is abundant in glial cells in the brain and CA type II isoform (CA II) activity in the hippocampus plays an important role in buffering extracellular pH transients produced by neural activity. Chronic ethanol exposure results in respiratory and metabolic acidosis, producing shifts in extracellular pH in the brain and body. These neurophysiological changes by ethanol are hypothesized to contribute to the continued drinking behavior and physical withdrawal behavior in subjects consuming ethanol chronically. We explored whether chronic ethanol self-administration (ethanol drinking, 10% v/v, ED) without or under the influence of chronic intermittent ethanol vapor (CIE-ED) experience alters the expression of CA II in the hippocampus. Postmortem hippocampal tissue analyses demonstrated that CA II levels were enhanced in the hilus region of the hippocampus in ED and CIE-ED rats. We used a novel molecule&mdash, 4-fluoro-N-(4-sulfamoylphenyl) benzenesulfonamide (4-FS)&mdash, a selective CA II inhibitor, to determine whether CA II plays a role in ethanol self-administration in ED and CIE-ED rats and physical withdrawal behavior in CIE-ED rats. 4-FS (20 mg/kg, i.p.) reduced ethanol self-administration in ED rats and physical withdrawal behavior in CIE-ED rats. Postmortem hippocampal tissue analyses demonstrated that 4-FS reduced CA II expression in ED and CIE-ED rats to control levels. In parallel, 4-FS enhanced GABAA receptor expression, reduced ratio of glutamatergic GluN2A/2B receptors and enhanced the expression of Fos, a marker of neuronal activation in the ventral hippocampus in ED rats. These findings suggest that 4-FS enhanced GABAergic transmission and increased activity of neurons of inhibitory phenotypes. Taken together, these findings support the role of CA II in assisting with negative affective behaviors associated with moderate to severe alcohol use disorders (AUD) and that CA II inhibitors are a potential therapeutic target to reduce continued drinking and somatic withdrawal symptoms associated with moderate to severe AUD.

Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a-4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1 H NMR and 13 C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+ /K+ -ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain.

Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR) and carbon-13 NMR (13C-NMR) and evaluated for neuroprotective potential using different pharmacological approaches. In vivo experiments demonstrated that ethanol triggered neurodegeneration characterized by impaired antioxidant enzymes and elevated oxidative stress. Furthermore, ethanol administration induced neuroinflammation, as demonstrated by elevated expression of tumor necrotic factor (TNF-&alpha, ), nuclear factor &kappa, B (NF-&kappa, B), cyclooxygenase-2 (COX2), and ionized calcium-binding adapter molecule-1 (Iba-1), which was further validated by enzyme-linked immunosorbent assay (ELISA). Treatment with 3a and 3b ameliorated the ethanol-induced oxidative stress, neuroinflammation, and memory impairment. The affinity of synthesized derivatives towards various receptors involved in neurodegeneration was assessed through docking analysis. The versatile nature of benzimidazole nucleus and its affinity toward several receptors suggested that it could be a multistep targeting neuroprotectant. As repetitive clinical trials of neuroprotectants targeting a single step of the pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles of neuroinflammation.

Stroke is the significant cause of human mortality and sufferings depending upon race and demographic location. Melatonin is a potent antioxidant that exerts protective effects in differential experimental stroke models. Several mechanisms have been previously suggested for the neuroprotective effects of melatonin in ischemic brain injury. The aim of this study is to investigate whether melatonin treatment affects the glutamate N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor signaling in cerebral cortex and striatum 24 h after permanent middle cerebral artery occlusion (MCAO). Melatonin (5 mg/kg) attenuated ischemia-induced down regulation of NMDA receptor 2 (NR2a), postsynaptic density-95 (PSD95) and increases NR2a/PSD95 complex association, which further activates the pro-survival PI3K/Akt/GSK3β pathway with mitigated collapsin response mediator protein 2 (CRMP2) phosphorylation. Furthermore, melatonin increases the expression of γ-enolase, a neurotrophic factor in ischemic cortex and striatum, and preserve the expression of presynaptic (synaptophysin and SNAP25) and postsynaptic (p-GluR1845) protein. Our study demonstrated a novel neuroprotective mechanism for melatonin in ischemic brain injury which could be a promising neuroprotective agent for the treatment of ischemic stroke.

We have reported that 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) reduces lipopolysaccharide (LPS)-induced hyperalgesia and allodynia in mice. The objective of the present study was to determine the effects of TQS on LPS-induced activation of hippocampal inhibitor of κB (IκB) and cluster of differentiation 11b (CD11b) gene expression involving hyperalgesia and allodynia in mice. We also examined the effects of TQS on microglial phenotype following LPS administration. Pretreatment of TQS (4 mg/kg) reduced the expressions of IκB and CD11b mRNA. Pretreatment of methyllycaconitine (3 mg/kg), an α7 nAChR antagonist, reversed TQS-induced decrease in IκB and CD11b mRNA expressions in the hippocampus indicating the involvement of α7 nAChR. In addition, TQS (4 mg/kg) reversed the LPS-induced microglial morphological changes. These results suggest that TQS reduces LPS-induced IκB and CD11b gene expression and microglial activation associated with hyperalgesia and allodynia by targeting microglial α7 nAChR in the hippocampus.

Withdrawal from chronic nicotine has damaging effects on a variety of learning and memory tasks. Various Sulfonamides that act as carbonic anhydrase inhibitors have documented role in modulation of various cognitive, learning, and memory processing. We investigated the effects of 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS) on nicotine withdrawal impairments in rats using Morris water maze (MWM), Novel object recognition, Passive avoidance, and open field tasks. Also, Brain-derived neurotrophic factor (BDNF) profiling and in vivo field potential recording were assessed. Rats were exposed to saline or chronic nicotine 3.8 mg/kg subcutaneously for 14 days in four divided doses, spontaneous nicotine withdrawal was induced by quitting nicotine for 72 h (hrs). Animals received 4-FBS at 20, 40, and 60 mg/kg after 72 h of withdrawal in various behavioral and electrophysiological paradigms. Nicotine withdrawal causes a deficit in learning and long-term memory in the MWM task. No significant difference was found in novel object recognition tasks among all groups while in passive avoidance task nicotine withdrawal resulted in a deficit of hippocampus-dependent fear learning. Anxiety like behavior was observed during nicotine withdrawal. Plasma BDNF level was reduced during nicotine withdrawal as compared to the saline group reflecting mild cognitive impairment, stress, and depression. Withdrawal from chronic nicotine altered hippocampal plasticity, caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results showed that 4-FBS at 40 and 60 mg/kg significantly prevented nicotine withdrawal-induced cognitive deficits in behavioral as well as electrophysiological studies. 4-FBS at 60 mg/kg upsurge nicotine withdrawal-induced decrease in plasma BDNF. We conclude that 4-FBS at 40 and 60 mg /kg effectively prevented chronic nicotine withdrawal-induced impairment in long term potentiation and cognitive performance.

Background: Epilepsy is one of the most common serious, life threatening neurological disorder. The current modern antiepileptic drug are associated with side effects, dependency, sedation, chronic toxicity, and teratogenic effects and in approximately 30% of the patients is ineffective.Ajwa datesare used as many traditional/classical medicine for the treatment of different diseases including convulsions and seizures. Methods:In this study, anticonvulsant effects of hydro alcoholic extract ofAjwa date fruit were examined by using pentylentetrazole (PTZ) model in mice.Thirty min. later to saline (10ml/kg), Ajwa date extract (200,400 mg/kg) and diazepam(1mg/kg) treatment, an i.p. dose of PTZ (90 mg/Kg) were given to all animals and each animal were observed for onset time of myoclonic jerks and tonic-clonic seizures, as well as duration of tonic-clonic seizures for 30 min via digital video camera. The animals will be also observed for mortality (% mortality = number of mice dead after convulsion/total number of mice used × 100). Results:Ajwa datesextract at the doses of 200,400 mg/kg prolonged the time of onset of seizure and decreased the duration of seizures compared to control (saline) group. Conclusions:It seems thatAjwa date have anticonvulsant effectand could be useful for the control and treatment of seizures. And in these effects, opioid receptors might probably be involved. More studies are needed in order to investigate its exact mechanism. Keywords:Ajwa dates, Seizure, Hydroalcoholic extract.

Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5–29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin. Electronic supplementary material The online version of this article (doi:10.1007/s00210-015-1145-y) contains supplementary material, which is available to authorized users.

We have reported that 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) reduces lipopolysaccharide (LPS)-induced hyperalgesia and allodynia in mice. The objective of the present study was to determine the effects of TQS on LPS-induced activation of hippocampal inhibitor of κB (IκB) and cluster of differentiation 11b (CD11b) gene expression involving hyperalgesia and allodynia in mice. We also examined the effects of TQS on microglial phenotype following LPS administration. Pretreatment of TQS (4 mg/kg) reduced the expressions of IκB and CD11b mRNA. Pretreatment of methyllycaconitine (3 mg/kg), an α7 nAChR antagonist, reversed TQS-induced decrease in IκB and CD11b mRNA expressions in the hippocampus indicating the involvement of α7 nAChR. In addition, TQS (4 mg/kg) reversed the LPS-induced microglial morphological changes. These results suggest that TQS reduces LPS-induced IκB and CD11b gene expression and microglial activation associated with hyperalgesia and allodynia by targeting microglial α7 nAChR in the hippocampus.

Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs.To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome.The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group.Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p 0. 05) and (F(2, 24) = 3.689, p 0.05), respectively. The plant extract in the acutely treated group reduced diarrhea (F(2, 24) = 4.850, p 0. 05 vs. saline). It decreased rectal temperature by chronic treatment at 30 min (F(2, 24) = 4.88, p 0.05), 60 min (F(2, 240 = 5.364, p 0.01) and 120 min (F(2, 24) = 4.907, p 0.05).This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan-induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti-inflammatory profile of PA. When tested against carbachol and K+ (80 mM)-induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose-dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca2+ concentration–response curves to the right, analogous to that produced by verapamil, confirming a Ca2+ channel blocker-like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose-dependent manner which was augmented by its prominent LOX inhibitory activity (IC50: 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions. Copyright © 2012 John Wiley & Sons, Ltd.

Evidence indicates that microglial activation contributes to the pathophysiology and maintenance of neuroinflammatory pain involving central nervous system alpha-7 nicotinic acetylcholine receptors. The objective of the present study was to determine the effects of 3a,4,5,9b-Tetrahydro-4-(1-naphthalenyl)-3 H -cyclopentan[ c ]quinoline-8-sulfonamide (TQS), an alpha-7 nicotinic acetylcholine receptor positive allosteric modulator (PAM), on tactile allodynia and thermal hyperalgesia following lipopolysaccharide (LPS)-induced microglial activation in hippocampus, a neuroinflammatory pain model in mice. In addition, we examined the effects of TQS on microglial activation marker, an ionized calcium-binding adapter molecule 1 (Iba-1), in the hippocampus may be associated with neuroinflammatory pain. Pretreatment of TQS (4 mg/kg) significantly reduced LPS (1 mg/kg)-induced tactile allodynia and thermal hyperalgesia. Moreover, pretreatment of methyllycaconitine (3 mg/kg) significantly reversed TQS-induced antiallodynic and antihyperalgesic responses indicating the involvement of alpha-7 nicotinic acetylcholine receptor. Pretreatment of TQS significantly decreased LPS-induced increased in hippocampal Iba-1 expression. Overall, these results suggest that TQS reduces LPS-induced neuroinflammatory pain like symptoms via modulating microglial activation likely in the hippocampus and/or other brain region by targeting alpha-7 nicotinic acetylcholine receptor. Therefore, alpha-7 nicotinic acetylcholine receptor PAM such as TQS could be a potential drug candidate for the treatment of neuroinflammatory pain.

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A3, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20-65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt-ext BM contained Bacoside A3 as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A3.

Neuropathic pain is a chronic neurological disorder characterized by hyperalgesia and allodynia. Recent evidence indicates that activation of immune system plays a critical role in the pathophysiol...

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A3, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20-65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt-ext BM contained Bacoside A3 as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A3.

The study was carried out to screen the crude methanolic extract (Me. Ext) of Pistacia integerrima bark for anti gastrointestinal (GIT) motility and analgesic activities. Toxicological study was also conducted for safety profile of the bark. Balb-C mice of either sex weighing 25 to 35 g (n=6) were used as experimental animal. The Me. Ext was safe at a dose of 1000 mgkg-1 body weight (b.w), however at a dose of 1500 mgkg-1 b.w it caused 66.6% death of experimental mice. Me. Ext at a dose of 50 mgkg-1 (35.20±15.22% inhibition) and 100 mgkg-1 (38.89±9.28% inhibition) significantly (p

The purpose of this paper is to evaluate the customer satisfaction of banking industry in Pakistan general, and Faisalabad particular, based on various levels of customer perception regarding service quality. This is an empirical study based mainly on primary data collected through a well-structured questionnaire. The questionnaire has been personally administrated on the a sample size of 132, chosen respondents on a convenient basis from four Pakistani banks, i.e. Alfalah Bank Limited, Faysal Bank Limited, National Bank Limited, and The Bank of Punjab. This paper makes a useful contribution as there are only few studies dealing with the assessment of service quality in conventional banking sector of Pakistan .The result indicates that customer perceive highest satisfaction in the responsiveness area and lowest in the tangibles area. In order to achieve higher levels of service quality, the bank managers should redesign their strategies about customer satisfaction with respect to service quality.

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan-induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti-inflammatory profile of PA. When tested against carbachol and K⁺ (80 mM)-induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose-dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca²⁺ concentration-response curves to the right, analogous to that produced by verapamil, confirming a Ca²⁺ channel blocker-like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose-dependent manner which was augmented by its prominent LOX inhibitory activity (IC₅₀ : 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions.

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance.