Search or add a thesis

Advanced Search (Beta)
Home > To Study the Effect of Salts and Complexes of Lead and Arsenic Metals on the Status of Thiols in Blood Components, Pharmacological and Toxicological Perspectives

To Study the Effect of Salts and Complexes of Lead and Arsenic Metals on the Status of Thiols in Blood Components, Pharmacological and Toxicological Perspectives

Thesis Info

Access Option

External Link

Author

Ullah, Naseem

Program

PhD

Institute

Gomal University

City

Dera Ismail Khan

Province

KPK

Country

Pakistan

Thesis Completing Year

2014

Thesis Completion Status

Completed

Subject

Applied Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/2141/1/2393S.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727615366

Similar


Heavy and transition metals have been widely known for their toxicities for centuries. Arsenic and Lead are highly valued in terms of toxicity to living systems due to their high affinity for sulfhydryl (-SH) containing residues. The chemical interactions of Arsenic and Lead with thiols (–SH rich molecules) results in numerous ill-health effects. As a part of this PhD thesis, the chemical status of GSH was determined in the presence of inorganic and organic complexes of lead and arsenic employing simple spectrophotometric analysis and 1H NMR methods. The behavior of Ellman’s reagent towards the metal-thiol chemistry was initially investigated to begin with the study of the changed status of thiols resulting from metal-thiol coordination. Chapter 2 describes the use of NMR methods to study the species in solutions. 1H NMR allowed us to identify additional components of the reaction mixture, their relative abundance and consequently the involvement of these additional Ellman’s based species in the spectrophotometric errors associated with the use of Ellman’s reagent. Using 1H NMR methods we are able to show that Ellman’s reagent can exchange with thiolates previously coordinated with lead and arsenic. In the context of this 1H NMR study, some limitations were found to be associated with the use of Ellman’s reagent in our study. Ellman’s reagent was found able to react with the thiols being previously attached with arsenic and lead, leading to an over estimation of the thiols in the solution systems. 4,4′-dithiodipyridine (DTDP) was adapted instead of Ellman’s reagent for the spectrophotometric determination of the mixtures involving metal-thiols complexes in aqueous solution and biological mixtures after establishing limitations associated with the use Ellman’s reagent in this capacity of the study. Chapter 3 describes the 1H NMR carried out to study the conditions and ratios of the complexed thiolates (complexes of both arsenic and lead with some important low molecular weight thiols (Glutathione, N. acetyl cysteine and D-Penicillamine). 1H NMR study presented in this chapter provides detailed information about the changes in the chemical status of GSH that might be the basis of this chemical change observed spectrophotometrically in the form of depletion. 1H NMR methods confirmed metal-thiol adducts (i.e., As-SG3 and Pb-SG2) to be the mechanism behind the GSH depletion in the presence of these metal compounds. After establishing the limitation associated with the use of Ellman’s reagent, 4,4′- dithiodipyridine was used for the spectrophotometric determination of the unbound thiols in the presence of complexed thiolates in aqueous solutions. In the course study presented in XII chapter 4, we have spectrophotometrically investigated the reactions of arsenic and lead with sulfhydryl containing thiols i.e., Glutathione, N-Acetyl cysteine and D-Penicillamine in aqueous solutions. In this chapter, the effects of arsenic (Sodium arsenite and Methylarsonous acid) and lead (Lead acetate and Lead acetyl acetonate) on low molecular weight thiols (Glutathione, N. acetyl cysteine and D-Penicillamine) have been spectrophotometerically quantitated in aqueous solutions. Employing influential variables (i.e., different metal concentrations, incubation times and pH ranges) to the study in aqueous solutions, prominent and regular decrease in the thiol levels were caused by each of the inorganic and organic compounds of arsenic and lead in spectrophotometric analysis. Chapter 5 describes the spectrophotometric estimation of important and most abundant low molecular weight thiol (Glutathione) in the whole blood and blood components (cytosolic Fraction and plasma) of human volunteer. In order to improve our understanding of the coordination chemistry of arsenic and lead in whole blood, cytosolic fraction and Plasma, a systematic study of the changes in glutathione (GSH) levels in these biological samples of healthy human volunteers, has been carried out. The effects of the inorganic and organic compounds of arsenic and lead on glutathione status in these biological samples have been spectrophotometerically evaluated by 4,4′-dithiodipyridine. Chapter 6 describes the spectrophotometric estimation of Glutathione in WBCs (Lymphocytes and Monocytes) isolated from human blood, while the study carried out in chapter 7 describes the estimation of Glutathione in liver isolated from rabbits. Chapter 8 describes the exchange of arsenic (AsIII) and lead (PbII) between Proteins (Albumin) and low molecular weight thiols (Glutathione, N. acetyl cysteine and D- Penicillamine). In addition to thiol disulfide exchange reactions, the exchange of arsenic and lead between Proteins (Albumin) and low molecular weight thiols (Glutathione, N. acetyl cysteine and D-Penicillamine) has also been investigated by Column chromatographic methods using Ellman’s reagent. The exchange behaviour of arsenic and lead between proteins and low molecular weight thiols have been analyzed spectrophotometrically by making use of Ellman’s reagent. Column chromatographic methods have been used to collect complexed proteins. The sulfhydryls present on the pure and complexed proteins have been estimated spectrophotometerically. The study regarding the thiol disulfide exchange reactions resulted that the low molecular weight thiolates (Reduced glutathione and N-acetylcysteine) take off As(III) and Pb(II) species which are attached to proteins. XIII Results from multiple studies presented in this PhD thesis are consistent to conclude and anticipate that lead and arsenic species are dynamic in nature as in the case of using Ellman’s reagent, thiolates could be removed from the coordination sphere of the arsenic and lead in As(SR)3 and Pb(SR)2 respectively and in the case involving albumin, the slow exchange of lead and arsenic species bound to cys-34 is the basis for a mechanism by which toxic species can become widely distributed around the body.
Loading...
Loading...

Similar Books

Loading...

Similar Chapters

Loading...

Similar News

Loading...

Similar Articles

Loading...

Similar Article Headings

Loading...

سید صادقؔ حسین

سید صادقؔ حسین
سید صادقؔ حسین (۱۸۹۸۔۱۹۸۹ئ) نام اور صادقؔ تخلص کرتے تھے۔ آپ کھادڑ پاڑہ (کشمیر) میں پیدا ہوئے۔ آپ کے والدین نے کشمیر سے ہجرت کر کے شکر گڑھ (سیالکوٹ) میں سکونت اختیار کی۔ آپ کے والد صفدر کاظمی نے وفاقی سیکرٹری کے عہدے پر کام کیا۔ تعلیم مکمل کرنے کے بعد آپ نے ظفر وال سے وکالت کا آغاز کیا۔ آپ تحریکِ پاکستان میں کارکن کے طور پر کام کرتے رہے۔ ۱۹۳۶ء میں آپ صدر مسلم لیگ شکر گڑھ مقرر ہوئے۔ آپ کا واحد شعری مجموعہ ’’برگِ سبز‘‘ کے نام سے شائع ہوا۔ (۲۶۰)
صادق کو صرف ایک شعر کی وجہ سے اردو شاعر ی میں شہرت ملی۔ بعض حضرات اس شعر کو علامہ محمد اقبال سے منسوب کرتے ہیں۔ یہ شعر ان کے شعری مجموعے ’’برگ سبز‘‘ کی ایک غزل میں موجود ہے۔ شعر ملاحظہ ہو:
تندیٔ بادِ مخالف سے نہ گھبرا اے عقاب
یہ تو چلتی ہے تجھے اونچا اڑانے کے لیے (۲۶۱)
صادقؔ نظم اور غزل کے شاعر ہیں۔ نظم پر اقبال کے اثرات ہیں اور غزل میں روایت کی جھلک نظر آتی ہے۔ ان کی شاعری میں قرآن مجید کے منظوم تراجم بھی موجود ہیں۔ انہیں اسلام سے سچی محبت ہے۔ اس محبت کا اظہار وہ خدائے بزرگ و برتر کی حمد و ثنا سے کرتے ہیں۔ وہ قرآن پاک کا ترجمہ کرتے ہوئے عام فہم اور سادہ زبان استعمال کرتے ہیں۔ ان کا اسلوب اتنا اچھا ہے کہ وہ ترجمہ معلوم نہیں ہوتا۔ کچھ اشعار ملاحظہ ہوں:
خداوندِ جہاں تیرے لئے تعریف ہے ساری
کہ ہے لطف و کرم تیرا ہر انس و جان پر جاری
تو ہی ہے مالک و مختارِ کل روزِ قیامت کا
ہر اک ہم میں سے دم بھرتا ہے تیری ہی عبادت کا
تری ہی ذات سے ہوتے ہیں ہم امداد کے طالب
تو...

مسالک کے مشترکات کے ادراک کی اہمیت: پاکستان کے تناظر میں تجزیاتی مطالعہ

Signaficance of the Understanding of Intra-faith Similerties: Analytical Study in the Context of Pakistan Muslims are commanded to foster unity as breaking into sects is forbidden by Allah. Islam teaches about broadness of vision and the emergence of different denominations in Islam is because of this broadness. There are different school of thoughts that emerged due to the broader perspective of Shar’ῑah rulings like Hanfῑ, Shᾱfῑ, Mᾱlikῑ and Hanblῑ, J'afrῑ etc despite that there is an essential unity in beliefs and practices among the Muslims. They all worship Allah, follow the last Messenger, Muhammad (ﷺ) and the last revelation Qur’an. They face the same Qibla while praying, prostrate to Allah five times a day, and believe in finality of prophet hood. Qur'an and Ahᾱdῑth are a source of jurisprudence for all Muslims. The difference between Muslims is in understanding and interpreting the Scripture and Ᾱhᾱdῑth of Prophet Muhammad (ﷺ) in the matters related with implementation of certain religious, social, political, and other duties. Islam rejects sectarianism, intolerance and extremism. Keeping in mind all of the above-mentioned points, in the article an attempt has been made to analyze the major challenges facing the intra-faith unity in Pakistan. The first is ignorance. Second is the role of media and scholars. Third is curriculum and fourth is intolerance. In the beginning the introduction of different schools of thought is given, and then forbearance demonstrated from the life of ‘Salaf Sᾱlihῑn’ has been described to establish an atmosphere of harmony in the present time, especially in Pakistan. The importance and significance of foundations of harmony is explained in such a manner that every Muslim should understand that the differences between the Muslims are very small, as they are only minor disagreements. Other than that, they are united in beliefs and practices. Finally, in the end, recommendations have been proposed.

Antimicrobial Resistance and Genotyping of Extended Spectrum Beta-Lactamase Producing Clinical Isolates

The development of resistance mechanism in Gram-Negative bacteria is growing all over the world affecting developing countries the most. Extended Spectrum Beta-lactamase (ESBLs) production is one of the widespread mechanisms of resistance associated with irrational or excessive use of extended spectrum cephalosporins. The ground objective of this study was to investigate the prescribing pattern of broad spectrum antibiotics in hospital setup and the prevalence of ESBL production in Gram-Negative clinical isolates collected from an outpatient source by both phenotypic and genotypic detection. The study also focused on the treatment options available to treat resistant clinical isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. Total 685 in-patient data were collected over a period of three months for the prescribing patterns of extended spectrum antibiotics used alone or in combination. The data were analyzed for the utilization of extended spectrum antibiotics in various wards either empiric or prophylactic use of broad spectrum cephalosporins. For the prevalence of ESBL production, 1005 clinical isolates of E. coli, K. pneumoniae, P. aeruginosa and P. mirabilis were collected from an out-patient source. Antimicrobial susceptibility and resistance patterns were determined by Kirby-Bauer disc diffusion method under the recommended guidelines of Clinical Laboratory Standard Institute (CLSI). Phenotypic detection of ESBL was performed on 352 clinical isolates using the double disc synergy test between amoxicillin/clavulanic acid (10μg) and ceftazidime or cefotaxime (30μg) disc. Multidrug resistance among ESBL positive isolates was also determined. Pearson’s or Fisher’s exact Chi-square test was used to analyze statistical association between ESBLs and Non ESBLs at 0.05 level of significance. Furthermore, polymerase chain reaction was used for the identification of TEM, SHV and CTX-M gene in ESBL positive clinical isolates. The prescribing pattern in hospital setup revealed that 75% of the overall antibiotics were prescribed for prophylactic treatments, whereas, among all prescribed antibiotics the frequency of broad spectrum cephalosporins alone or in combination was found to be the highest. Out of 1005 gram-negative clinical isolates, prevalence was found to be E. coli 680 (67.66 %), K. pneumoniae 248 (24.67%), P. mirabilis 3 (0.3 %) and P. aeruginosa XIII 74 (7.36%). Out of 352 clinical isolates, 96 (27.27%) were ESBL positive, female preponderance was found in 62 (67%), whereas 32 (33%) were males. E. coli was the most prevalent ESBL producers 79 (82%), followed by K. pneumoniae 16 (17%) and P. mirabilis 1 (1%). The urinary tract infections were the most commonly recovered infections i.e., 72 (75%), and among them 63 and 9 were E. coli and K. pneumoniae respectively. Age groups of 16-30 and 46-60 years were most affected with ESBL producing uropathogenic E. coli with a high prevalence in females. A high rate of resistance was observed against broad spectrum cephalosporins, fluoroquinolones, amoxicillin/clavulanic acid, sulfamethoxazole/trimethoprim and ampicillin. Whereas, amikacin, imipenem, tazobactam/piperacillin and fosfomycin were found effective antibiotic choices. The rate of multidrug-resistance was found to be 95%, 62.5% and 100% in ESBL producing E. coli, K. pneumoniae and P. mirabilis respectively. Statistical evaluation between ESBLs and Non ESBLs revealed significant association in E. coli (p 0.0004) and K. pneumoniae (p 0.032). Genotype identification revealed the presence of TEM, SHV and CTX-M genes in 82.14% (69/84) of the isolates. CTX-M was the most prevalent gene found in 59.5% (50/84) of the isolates, followed by TEM 41.6% (35/84) and SHV 13% (11/84). CTX-M was dominant among uropathogenic E. coli related to community acquired urinary tract infections. The study concluded an increased prevalence rate of ESBLs in E. coli, most of them recovered from urinary tract infections. The study also found an increased rate of multidrug-resistance among Gram-Negative clinical isolates. These incidences can be reduced by the restricted use of broad spectrum cephalosporins. The spread of ESBL producing uropathogenic E. coli can be controlled by implementing ESBL screening along with limiting the use of empiric therapy. Nevertheless, hygienic practices must be employed to reduce the incidence of community onset urinary tract infections.