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
There are risks and benefits with all medicines and estrogen replacement is no exception. In fact, estrogen replacement is one of the most controversial topics in Endocrinology. Anastatica hierochuntica L. is a popular treatment for the management of female reproductive disorders. The present research highlights the effect of aqueous extract of plant against conjugated estrogen(Premarin) in rabbits. Femal oryciolagus cuniculus rabbits were divided into four groups: the 1 st group, rabbits were orally administered (using a feeding solution )with daily dose(5 mL distilled water)for two months, the 2nd group, the rabbits were treated with conjugated estrogen (50 µg/kg b.w, body weight )for one month. The 3rd group, the rabbits were treated w
... Show MoreBackground: Diabetic neuropathy can affect any peripheral nerve, including sensory neurons, motor neurons, and the autonomic nervous system. Therefore, diabetic neuropathy has the potential to affect essentially any organ and can affect parts of the nervous system like the optic nerve, spinal cord, and brain. In addition, chronic hyperglycemia affects Schwann cells, and more severe patterns of diabetic neuropathy in humans involve demyelization. Schwann cell destruction might cause a number of changes in the axon. study aims to evaluate serum myelin protein level as a predicting marker in the diagnosis of diabetic neuropathy and to prevent early neuropathy complications of type 2 diabetes.
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Introduction and Aim: Forkhead box P3 (FOXP3) and interleukin-10 (IL-10) are the key regulators controlling the activity of Treg cells, which are crucial for maintaining immune tolerance and reducing autoimmune reactions. The objective of this study was to investigate the potential utility of elevated levels of FOXP3 and IL-10 gene expression as a diagnostic indicator in patients with rheumatoid arthritis (RA). Materials and Methods: The study used quantitative polymerase chain reaction (qPCR) to examine the expression levels of FOXP3 and IL-10 transcripts in whole blood samples from Iraqi patients with rheumatoid arthritis. A group of healthy control subjects were also included in the study. Results: In blood samples taken fr
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Chromium tanned leather wastes (CTLW) and vegetable tanned leather wastes (VTLW) were used as adsorbent materials to remove the Biebrich scarlet dye (BS), as an anionic dye from wastewater, using an adsorption method. The effects of various factors, such as weight of leather waste, time of shaking, and the starting concentration of Biebrich scarlet dye, temperature and pH were studied. It described the adsorption process using Langmuir and Freundlich isotherm models. The obtained results agreed well with the Langmuir model, and the maximum adsorption capacities of CTLW and VTLW were 73.5294 and 78.1250 mg.g⁻¹, respectively, suggesting a monolayer adsorption process. The adsorption kinetic was found to follow a pseudo-second-order kinetic
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Colonialism radically transformed the cultures of colonized peoples, often rupturing Indigenous traditions and folklore. Whether creating colonial discourse, promoting orientalist literature, advocating western educational institutions, or through biased media representations, imperial powers systematically oppressed Indigenous and Native peoples. Subjugated communities, however, created, and still form postcolonial discourse from their knowledge systems. This discourse insists on Indigenous and Native culture as central to Indigenous and Native peoples identity. This study examines the postcolonial literature of three groups: Kānaka Maoli, African Americans, and Iraqis. The scope of this dissertation scrutinizes how folklore is employed
... Show MoreBacterial infections pose an ongoing challenge due to resistance developed by infectious bacteria. So much research targeting designing new antibacterials is published annually. Our goal is to synthesize compounds that have given antibacterial activity according to molecular docking against the chosen target protein and that have acceptable ADMET properties that can be synthesized and used in the future. New 2-(5-methoxy-1-(4-chlorobenzene)-2-methyl-1H-indol-3-yl)acetohydrazide derivatives’ antibacterial efficacy against two common strains of Gram-negative and Gram-positive microorganisms has been developed, produced, and investigated. Sophisticated, modern analytical methods, including ATR-FTIR and 1H NMR spectroscopy, were used
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Atorvastatin have problem of very slightly aqueous solubility (0.1-1 mg/ml). Nano-suspension is used to enhance it’s of solubility and dissolution profile. The aim of this study is to formulate Atorvastatin as a nano-suspension to enhance its solubility due to increased surface area of exposed for dissolution medium, according to Noyes-Whitney equation.
Thirty one formulae were prepared to evaluate the effect of ; Type of polymer, polymer: drug ratio, speed of homogenization, temperature of preparation and inclusion of co-stabilizer in addition to the primary one; using solvent-anti-solvent precipitation method under high power of ultra-sonication.
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Anastatica Hierochuntica L. Used As an Alternative of Conjugated Estrogen (Premarin) in Rabbit Females
The gas sensing properties of Co3O4 and Co3O4:Y nano structures were investigated. The films were synthesized using the hydrothermal method on a seeded layer. The XRD, SEM analysis and gas sensing properties were investigated for Co3O4 and Co3O4:Y thin films. XRD analysis shows that all films are polycrystalline in nature, having a cubic structure, and the crystallite size is (11.7)nm for cobalt oxide and (9.3)nm for the Co3O4:10%Y. The SEM analysis of thin films obviously indicates that Co3O4 possesses a nanosphere-like structure and a flower-like structure for Co3O4:Y.
The sen
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