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Home > Study of Pyocyanin Induced Virulence & Pathogenicity of Nosocomial Infectious Agent Pseudomonas Aeruginosa and its Prevention

Study of Pyocyanin Induced Virulence & Pathogenicity of Nosocomial Infectious Agent Pseudomonas Aeruginosa and its Prevention

Thesis Info

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Author

Rashid, Muhammad Ibrahim

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Bio sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11444/1/Muhammad%20Ibrahim%20Rashid%20applied%20bioscience%202019%20NUST.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727389816

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Pseudomonas aeruginosa is a ubiquitously distributed and often, nosocomial infectious agent. It is identified as one of the top three nosocomial infectious agents, causing complicated and persistent infections. It has notorious infection feactures such as biofilm formation and antibiotic resistance, making it a significant healthcare challenge. P. aeruginosa is equipped with a diversified arsenal of virulence factors which help in infection establishment and progression against the host immune system. Among many other, P. aeruginosa produces Pyocyanin (PCN), a redox active blue phenazine pigment, considered to be its primary virulence factor. This blue pigment plays a critical role in infection establishment and survival of the pathogen. Studies have implicated PCN with multiple bioactive properties due to its redox active potential, i.e. immuno-modulation, pro-apoptotic, enzyme inactivation and others. The ability to diffuse through biological membranes imparts a new dimension for PCN mediated virulence of P. aeruginosa in the host body. So far PCN mediated virulence has been considered as localized incidence at the site of infection i.e. effect of PCN on the ciliary movement of epithelial lining or inactivation of DUOX1 enzyme in the respiratory system. The emergence of Pan-drug resistant or ‘Superbug strains’ at pandemic scale is a critical threat to health care setups. The ineffectiveness of antibiotics against P. aeruginosa puts the vulnerable groups at serious risk as the World Health Organization is foreseeing the dawn of Post-antibiotic era. Lack of preventive vaccines against P. aeruginosa is another challenge that puts vulnerable groups at greater risk. A comprehensive strategy was devised to better understand PCN mediated P. aeruginosa virulence. This dissertation reports the potential impact of PCN in Central Nervous System during P. aeruginosa infection. Cytotoxic impact of PCN was studied in murine models. Blood brain barrier permeability was assessed computationally and confirmed via HPLC. Murine behavioral tests demonstrated neurodegenerative and cognitive impairment potential of PCN. Systemic redox potential was evaluated by employing multiple in silico tools and glutathione-S-transferase assay, PCN-induced oxidative stress in brain, lungs and cardiac tissues. For dealing with PCN-mediated virulence, PCN biosynthesis was targeted via drug repurposing in a dual manner: 1) Study of PCN chemical-protein and drug drug interactions revealed Piperaquine as an anti-virulence therapeutic agent as it has an effective anti-PCN potential. While the structure based study demonstrated aspirin’s potential in inhibiting PCN, unlike ibuprofen. 2) Innate immune component DUOX1 and its homologue NOX4 capable of inactivation of PCN were computationally studied for their sequential, structural and functional aspects, and were annotated. These two schemes could contribute towards the development of Pseudomonas specific anti-virulence approaches independent of antibiotic resistance phenomenon. In a bigger scenario genomic data was explored for dealing with the antibiotic resistance challenge. Using reductive genomic screening, potential peptide vaccine candidates and prospective novel drug targets were predicted. This dissertation focuses on PCN mediated virulence of P. aeruginosa and strategies for prevention and management of infection.
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اردو تنقید کا ارتقا

موضوع 10:اردو تنقیدکا ارتقا
تنقید کے پس منظرکاپہلانظریہ :
بعض لوگوں کے مطابق اردو تنقید کا آغاز تذکروں سے ہوتا ہے۔ اس سلسلے میں فارسی زبان میں۱۷۶۷ء یں فارسی زبان میں چھپنے والے میر تقی میر کے تذکرے "نکات الشعراء " کو سب سے پہلا تذکرہ تسلیم کیا جاتا ہے۔ اس میں اردو شاعروں کے حوالے سے لکھا گیا تھا۔اردو زبان میں پہلا تذکرہ ۱۸۰۸ء میں 'مرزا علی لطف 'نے" گلشن ہند "کے نام سے لکھا۔
تنقید کے پس منظرکادوسرانظریہ :
تمام ناقدین متفقہ طور پر۱۸۹۲ئمیں مولانا الطاف حسین حالی کے لکھے گئے "مقدمہ شعر و شاعری "کو تنقید کا نقطہ آغاز سمجھتے ہیں۔ ادب کی روایات پروان چڑھتے ہوئے۱۳۰سال میں ہماری تنقید نے جس رفتار سے ترقی کی ہے وہ بے مثال ہے اور اردو تنقید کی قابل رشک ترقی کا کسی بھی دوسری زبان سے موازنہ کیا جا سکتا ہے۔۱۸۹۲ئسے پہلے ایک مورخ اور بھی ہیں جن کا نام محمد حسین آزاد ہے۔ان کے لیکچر ز جو انہوں نے انجمن پنجاب کے پلیٹ فارم سے دیئے۔ان کو کتابی صورت میں 'آب حیات' میں اکٹھا کیا گیا۔بعض ناقدین کے مطابق مولانا حالی سے قبل ہی محمد حسین آزاد نے اردو تنقید کی بنیاد رکھ دی تھی۔
تنقید کے پس منظرکاتیسرانظریہ :
اردو تنقید کا آغاز استادی شاگردی کے اداروں اور مشاعروں اور مجلسی تنقید سے ہوا۔اس نظریے کے مطابق اردو شاعری اور تنقید کا آغاز ایک ساتھ ہوا۔ نئے تخلیق کار مشاعروں میں اپنی تخلیق پیش کرتے اور سامعین اس کی خوبیاں و خامیاں بیان کرتے ہیں۔اسے مجلسی تنقید کہتے ہیں۔اس لیے جب سے اردو شاعری شروع ہوئی ہے تب سے اردو تنقید کا آغاز ہوا ہے۔کلیم الدین احمد سمیت متعدد نقاد تذکرہ نگاری کو تنقید نہیں مانتے اس اعتبار سے آب حیات تک ہونے والی تنقید کو تنقید کا پس منظر توکہا جاتا ہے لیکن...

Al-Sukākī’s Classification of Metaphor and Qurānic Discourse

The present study is divided into two main sections; the first section will give a general overview about the figurative language and more focus on metaphor (istiᶜārah in Arabic) because the metaphor is considered as one of the most literary devices and the main category of the figurative language. So in this study has given various definitions of figurative language and metaphor according to Muslims and Non-Muslims linguists and along with this explained Al-sukākī’s classification of metaphor which is little close to Al-Jurjānī’s classification of metaphor and view respectably among Muslims and Non-Muslims linguists. The second section of this study deals with metaphors given in Holy Qur'ān, which are denoted according to Al-sukākī’s classification in this respect. In this reference the verses are presented with detailed tafsīrī literature so the reader could well comprehend the purposes and the classical aspect of metaphors in text and also could evaluate linguistic architecture of  Holy Qur'ān.

International Trade Challenges and Opportunities for Pakistan Cotton-Textile and Apparel Sector

The purpose of this research was to provide a comprehensive analysis of international trade in order to evaluate and determine the challenges it poses, and opportunities, it offers to Pakistan’s Cotton, Textile and Apparel Sector. The research is based on secondary data sources. World Bank, WTO, UNCTAD, and a lot of other valuable and authentic reports from the authors of repute have been consulted to understand the increasingly complex international trade relations in a globalizing world. Volumes of government reports, position papers, handouts and books have been searched to appreciate the dynamics of Pakistan Cotton, Textile and Apparel Sector. The research thesis endeavors to capture where the challenge is. What is at stake? Who are the players? What are the opportunities in the international market place? How these challenges can be translated in to opportunities? Brief account of recent trade development and the relationship between global and domestic trading arrangements have been discussed. Role of politics in shaping decisions and managing power both at domestic and global level, significance of international commitments, and influence of historical, cultural back grounds, shared ideas and beliefs, and individual mind set in competing interests in the domestic economy have also been dilated upon. Analytical findings reveal that Pakistan has comparative edge on the basis of comparative advantage, reveal comparative advantage, relative trade advantage, and trade complementarities. The estimated value of revealed comparative advantage of cotton in Pakistan is 18 which is very high than unity which implies that Pakistan has great opportunities in the export of cotton and cotton manufacturing. Moreover, the estimated values of balasa and Lafay index for all cotton and cotton products are very high which reveal that Pakistan has trade competitiveness in the cotton and cotton manufacturing. The estimated value of relative trade index for primary products, cotton seed, cake of cotton seed and cotton linter, are positive which imply that these products are highly competitive, while oil of cotton seed and cake of cotton seed are uncompetitive. Furthermore, the value of trade complementarities variable for USA, EU, Japan and Canada (trading countries) are greater than unity except SAARC countries. This means that trading with SAARC countries in cotton and cotton products is less profitable as compared to other countries where cotton trading is highly profitable. Still domestic resource cost analysis (DRC) proves that Pakistan has greater opportunities in cotton production. The values of reveal comparative advantage and relative trade advantage further suggest that Pakistan has greater opportunities and prospects for exporting cotton and cotton manufacturing. Similarly trade complementarities show and suggest that Pakistan should focus on Middle East market with highest trade complementarities, followed by Canada, USA, EU, SAARC countries and then Japan. Bt transgenic cotton is widely grown in the cotton growing areas of Sindh and Punjab. Bt cotton can play a significant role to enhance agricultural productivity as the productivity of cotton in Pakistan is 0.5 ton/ha as compared productivity of Bt cotton in China is 9 ton/ha which implies a huge cotton productivity gap. This gap can be narrowed down by the adoption of Bt cotton in Pakistan which will have major impact on food security efforts in the country. Urgent efforts are required to focus on cost efficiency, higher productivity with quality of cotton, export diversification of cotton products, export oriented policy and market perspective to become more competitive in the global cotton market. There is also a need to strengthen the cotton - textile value chain with back ward and forward linkages. Unique products have to be developed, and a shift from comparative advantage to competitive advantage is the way forward.