Faculty Of Pharmacy Graduation Project 2019 - 2020
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Browsing Faculty Of Pharmacy Graduation Project 2019 - 2020 by Subject "Biochemistry"
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Item Evaluating the Role of CAMP in Sleep Deprivation(MSA university Faculty of pharmacy, 2020) Raafat, Clara; Gerges, John; Emad, Kirolos; Wagdy, MariaSleep deprivation is a condition of disrupted sleep cycle, it happens when an individual does not get enough sleep necessary for the individual to wake up alert enough during the day. It can be acute or chronic. Some of the causes of sleep deprivation are imposed on the individual as the nature of his/her occupation and working schedule, health conditions, use of some drugs and insomnia. Other causes are related to habits or individual responses as excessive alcohol consumption, personal obligations and emotional stress. cAMP is an important secondary messenger and it regulates a lot of functions in the human body. Rolipram is a phosphodiesterase-4 inhibitor and should prevent the hydrolysis of cAMP. On the other hand the action of chlorogenic acid is to activate calcineurin which inactivates the DARPP-32 thus allowing the dephosphorylation of protein kinase A and reversing the action of cAMP. The aim of this study is to investigate a different mechanism by which cAMP affects sleep deprivation and the effects of its elevation on memory and the learning abilities of sleep deprived mice using rolipram and chlorogenic acid. Induction of sleep deprivation test used in this study by flower pot method dividing the mice into four groups each group consists of six mice. Mice injected with the corresponding treatment and their learning memory tested with Morris water maze. Hippocampus screening is used for the assay of cAMP and Nrf-2 using ELISA. GSK3β, CREB and PKA levels are measured by Western Blot technique. The results showed that the rolipram inhibits the degradation of cAMP that activates the PKA pathway the level of GSK3-beta, NFR2 and the CREB increased. In conclusion, activation of cAMP leads to improvement of memory, increase of cognition abilities and decrease in inflammation and oxidative stress. On the other hand cholorgenic acid has opposing mechanism against rolipram which leads to decrease in the levels of GSK3-b, NFR2 and CREB.Item Genetic Basis Associated with Osteoporosis: An in-vivo Study(MSA university Faculty of pharmacy, 2020) Hossam ELdeen Khalil, Bouthaina; Sherif Aly, Nourhan; Naser Salah, Mariam; Taher Salem, ZinaOsteoporosis is a very common disease that affects the bones and is characterized by decreased bone mineral density, as a result of impaired bone mineralization. Consequently, patients suffering from osteoporosis are highly prone to fractures, which sometimes can be life-threatening. Usually, patients suffering from osteoporosis have no symptoms until the first fracture occurs. Osteoporosis is primarily diagnosed by low Bone Mineral Density (BMD), which is assessed using DEXA scan. Besides bisphosphonates, which are used as the first line of treatment for osteoporosis, Selective Estrogen Receptor Modulators (SERMs) are also commonly used. Lately, studying the pathogenesis of osteoporosis on the molecular level has gained more attention. Several miRNAs, genes and epigenetic modifications have been linked to osteoporosis. This allows for better understanding of the disease incidence, progression, and treatment. The main aim of this work is to study the molecular mechanisms fundamental for the progression and treatment of osteoporosis. Using bone samples from established osteoporotic rat models, we investigated the role of WNT-signalling pathway in osteoporosis development and treatment, in addition to the role of histone acetylation and miR-148a-3p in progression and treatment of the disease. Our study suggests that WNT-signalling pathway is inhibited during the progression of osteoporosis; and that upon treatment, WNT-signalling recovers to close-to-normal levels. Our work also indicates that the extent of histone acetylation of WNT-1 gene, and the level of miR- 148a-3p, could be involved in the regulation of WNT-signalling pathway during the progression and treatment of osteoporosis. Taken together, our results show that targeting WNT-signalling pathway for the development of future treatments for osteoporosis seems to be a realistic option.Item Stem Cells; a Promising Candidate for Treatment of Rheumatoid Arthritis.(MSA university Faculty of pharmacy, 2020) Amir Ali, Alia; Ashraf Mohamed Abd El Hakam, Amira; Khaled Mostafa, Esraa; Sayed Sayed Ahmed, MaryamThe proposed aim is to investigate the effect of mesenchymal stem cells in the treatment of rheumatoid arthritis. On the other hand, the objective involves brief discussion on the pathophysiology of rheumatoid arthritis, stem cells and their isolation scheme as well as method of disease induction. Moreover, it also involves the investigation of disease parameters and exploring the modulatory effect of mesenchymal stem cells on RA. The methodology applied to achieve the previously mentioned objective and aim, by induction of the disease through intradermal injection of complete Freund`s adjuvant, followed by measuring the arthritis score to ensure RA development. Afterwards, the isolation of MSCs from healthy rats` femur, and using ten healthy male albino rats dividing them into five groups; negative control, positive controls and the other three were diseased groups treated differently after disease incidence, by giving sterile saline for control groups, methrotrexate for third group, mesenchymal stem cells for the fourth and both for the last group. At the end of treatment period, the levels of interleukin 1, 10, TNFα and interferon were measured using ELISA in serum. Moreover, real time PCR was used to detect the following genes: alkaline phosphatase (mALP), transcription factor sp7 (mOsterix) and collagen type I or alpha 1 (mCOL-I). Finally, comet assay was also employed to assess the degree of damage or repair to the DNA. The results showed significant increase osteogenic markers and IL-10; and significant reduction in proinflammatory cytokines, %T, TM and OTM values in the MSC group when compared to the other groups (P<0.05). To sum up, this study illustrated that MSC showed a beneficial role in the treatment of RA through its anti-inflammatory and immunosuppressive properties. Moreover, it had a favorable role when combined with MTX as it provided better prognosis than when MTX is used alone.