Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system). View full metadata
Alpha-tocopherol acetate is one of the most important vitamin E derivatives,that were used as antioxidants. Adsorbents like kaolin, magnesium carbonate, and microcrystalline cellulose were used successfully to incorporate oily alpha-tocopherol acetate into an acceptable powder dosage form. The results revealed that microcrystalline cellulose as an adsorbents gave the best results with 50% loading capacity at time, 8 minutes before and after incubation period (3 months at 30C°), while kaolin and magnesium carbonate have been shown a significant difference before and after incubation. Addition of 1% w/w magnesium carbonate to the kaolin enhanced the loading capacity by decreasing the time of adsorption from 20 to 6 minutes and 47
... Show More
Metoclopramide HCl (MTB) is a potent antiemetic drug used for the treatment of nausea and vomiting. Many trials were made to prepare a satisfactory MTB orodispersible tablet using direct compression method.Various super disintegrants were used in this study which are croscarmellose sodium (CCS), sodium starch glycolate (SSG) and crospovidone (CP). The latter was the best in terms of showing the fastest disintegration time in the mouth.Among the different diluents utilized, it was found that a combination of microcrystalline cellulose PH101 (MCC 101), mannitol, dicalcium phosphate dihydrate (DPD) and Glycine was the best in preparing MTB orodispersible tablet with fastest disintegration time in the mouth.The physical parameters of the pre
... Show More
(1)
Conflict, peace, and sports have a long history as practical realities, and their correlation has become an important subject of study in the last decades of the twentieth century. Sport has infiltrated peace and conflict studies as a tool for resolving conflict and building peace, but opinions have differed between those who say it is a positive tool and others who see it as negative. The Gulf Cup is one of the champions that have never been studied, and in-depth research about it has not been done. This tournament has affected the relations between the states involved. The politics cast its shadow on the Gulf Cup. The paper aims to shed light on how political events in the region have consistently affected the Gulf Cup and how politics in
... Show More
The concept of education is not actually restricted to children or school students, but rather every person should be educated and followed up if he is intended to grow and prove, with effort and time allocation as to fulfill that goal. Thus , the current paper aims to a thinking education and to educate that thinking in teacher and it is not new to deal with the personal characteristics of teacher in the different scientific , and educational researches . But ,these research did not address the necessity of acquiring the skill of thinking, especially as it affects teacher's presentation of the content of the curriculum or even content outside the curriculum, and therefore, there is n
... Show More
(3)
(2)
The mucilage from the seeds of Lallemantia royleana family Labiatae was extracted and subjected to preformulation study for evaluation of its suitability for use as suspending agent. Furosemide suspensions were prepared using (1.5% w/v) of the extracted Lallemantia royleana mucilage, (1.5% w/v) chitosan and (0.35% w/v) xanthan gum. The mucilage was white in color and the average yield of dried mucilage obtained from L.royleana nutlets was 14 % w/w of the seeds used. It is sparingly soluble in water but swells in contact with it, giving a highly viscous solution. It is slightly acidic to neutral. It was found that the extracted natural mucilage of Lallemantia royleana exhibited a higher viscosity profil
... Show More
(8)
The ability of using aluminum filings which is locally solid waste was tested as a mono media in gravity rapid filter. The present study was conducted to evaluate the effect of variation of influent water turbidity (10, 20and 30 NTU); flow rate(30, 40, and 60 l/hr) and bed height (30and60)cm on the performance of aluminum filings filter media for 5 hours run time and compare it with the conventional sand filter. The results indicated that aluminum filings filter showed better performance than sand filter in the removal of turbidity and in the reduction of head loss. Results showed that the statistical model developed by the multiple linear regression was proved to be
valid, and it could be used to predict head loss in aluminum filings
Worldwide, hundreds of millions of people have been infected with COVID-19 since December 2019; however, about 20% or less developed severe symptoms. The main aim of the current study was to assess the relationship between the severity of Covid-19 and different clinical and laboratory parameters. A total number of 466 Arabs have willingly joined this prospective cohort. Out of the total number, 297 subjects (63.7%) had negative COVID-19 tests, and thus, they were recruited as controls, while 169 subjects (36.3%) who tested positive for COVID-19 were enrolled as cases. Out of the total number of COVID-19 patients, 127 (75.15%) presented with mild symptoms, and 42 (24.85%) had severe symptoms. The age range for the partic
... Show More
The synthesis of nanoparticles (GNPs) from the reduction of HAuCl4 .3H2O by aluminum metal was obtained in aqueous solution with the use of Arabic gum as a stabilizing agent. The GNPs were characterized by TEM, AFM and Zeta potential spectroscopy. The reduction process was monitored over time by measuring ultraviolet spectra at a range of λ 520-525 nm. Also the color changes from yellow to ruby red, shape and size of GNP was studied by TEM. Shape was spherical and the size of particles was (12-17.5) nm. The best results were obtained at pH 6.
(4)
(2)