subject:(pharmacology)

Temple University

1. Fang, Pu. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.

Degree: PhD, 2012, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,223888

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Pharmacology

Homocysteine (Hcy) is a thiol amino acid formed upon methionine de - methylation. A number of studies have revealed an association between hyperhomocysteinemia (HHcy),… (more)

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Pharmacology

Homocysteine (Hcy) is a thiol amino acid formed upon methionine de - methylation. A number of studies have revealed an association between hyperhomocysteinemia (HHcy), in which plasma Hcy levels exceed 15 µM, and diabetic atherosclerosis [1]. Despite these associations, the mechanisms underlying HHcy - associated diabetic atherosclerosis have not been clearly defined. This study assessed the effect of HHcy on diabetic atherosclerosis and its underlying mechanisms. We established a mouse model with a combination of three metabolic disorders, including HHcy (to mimic human HHcy), hyperglycemic (to mimic type 1 diabetes) and dyslipidemia (to exacerbate ApoE-/- mouse's susceptibility to atherosclerosis). In this mouse model, severe HHcy was developed due to mouse Cbs deficiency (mean plasma Hcy 182 µM) in a noval HHcy mouse model (Tg-hCBS Cbs ApoE-/-) generated by our collaborator [2]. Hyperglycemia was developed by 50 mg/kg streptozotocin (STZ) consecutive injection for 5 days (mean blood glucose 397 mg / dL). Dyslipedimia was introduced by high fat (HF, 21.0 % by weight) diet to accelerate aortic lesion formation in the Tg-hCBS Cbs ApoE-/- mice. An inducible human CBS (hCBS) transgene (Tg) was introduced to circumvent the neonatal lethality due to the mouse Cbs deficiency (Tg-hCBS Cbs-/- ApoE-/- mice). A zinc supplement in water could induce hCBS transgene expression and reverse Hcy level (reduced plasma Hcy from 182 µM to 5 µM, p < 0.001). Severe HHcy aggravated metabolic abnormalities, including increased urine secretion (from 8.35 ± 6.81 g/d/mouse in hyperglycemia only mice to 21.14 ± 5.95 g / d / mouse in hyperglycemic HHcy mice, p=0.042), increased water consumption (from 27.28 ± 9.46 g / d / mouse to 44.20 ± 4.66 g / d / mouse, p = 0.026), increased blood glucose level (from 443.20 ± 107.82 mg / dL to 614.27 ± 199.36 mg/dL, p = 0.031), increased heart weight (from 0.08 ± 0.02 g / cm to 0.11 ± 0.03 g / cm, p = 0.031) (data not shown) and decreased body weight (from -0.05 ± 0.92 g / 2 weeks / mouse to -1.78 ± 2.38 g / 2 weeks / mouse, p = 0.017). Hcy-lowering by zinc water reversed HHcy - induced hyperglycemia (from 614.27 ± 199.36 mg / dL to 440.20 ± 134.37 mg / dL, p = 0.032), increased urine secretion (from 21.14 ± 5.95 g / d / mouse to 0.90 ± 1.24 g / d / mouse, p = 0.042), and increased water consumption (from 44.20 ± 4.66 g / d / mouse to 6.08 ± 1.84 g / d / mouse, p = 0.008) in hyperglycemic mice. Increased atherosclerotic lesions were also found in the aortic roots of hyperglycemic HHcy mice (from 30.38 ± 14.34 % of the lumen area to 48.18 ± 12.07 %, p = 0.040). Increased accumulation of monocytes (MCs) and inflammatory MCs were found in atherosclerotic lesions of hyperglycemic HHcy mice. By sequential double immune - fluorescence staining with monoclonal antibodies (mAbs) anti MOMA - 2 (MC / macrophage [MØ] marker) and anti - Ly6C (inflammatory MC marker), we found that hyperglycemic HHcy mice had the largest area and percentage of MC / MØ (MOMA - 2+), and the largest area and percentage…

Advisors/Committee Members: Wang, Hong;, Yang, Xiao-Feng, Merali, Salim, Autieri, Michael V., Ashby, Barrie, Kruger, Warren D.;.

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fang, P. (2012). HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,223888

Chicago Manual of Style (16^th Edition):

Fang, Pu. “HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.” 2012. Doctoral Dissertation, Temple University. Accessed December 15, 2019. http://digital.library.temple.edu/u?/p245801coll10,223888.

MLA Handbook (7^th Edition):

Fang, Pu. “HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.” 2012. Web. 15 Dec 2019.

Vancouver:

Fang P. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2019 Dec 15]. Available from: http://digital.library.temple.edu/u?/p245801coll10,223888.

Council of Science Editors:

Fang P. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. [Doctoral Dissertation]. Temple University; 2012. Available from: http://digital.library.temple.edu/u?/p245801coll10,223888

Temple University

2. Pansuria, Meghanaben. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.

Degree: PhD, 2013, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,228447

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Pharmacology

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). Both HHcy and insulin resistance (IR) are associated with atherosclerotic CVD. Recent studies… (more)

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Pharmacology

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). Both HHcy and insulin resistance (IR) are associated with atherosclerotic CVD. Recent studies have confirmed that insulin is not only a principle regulator of glucose homeostasis but also an important vasoactive hormone involved in the modulation of vascular tone. Epidemiological studies and animal studies have demonstrated the positive correlation of HHcy with IR and diabetes. Nevertheless, the effect and mechanism of HHcy on endothelial insulin signaling and insulin resistance has not been studied. In this study, we investigated the role and mechanism of HHcy on endothelial IR in vivo using transgenic mouse model of HHcy (Tg-hCBS Cbs -/- mice, plasma Hcy levels of 102.6 ± 9.1µmol/L) and in vitro using human aortic endothelial cells (HAEC). Using bioinformatics approach, we found tissue differential expression of Insulin/PI3K pathway genes in human and mouse. Furthermore, we measured tissue Hcy, S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH) levels in Tg-hCBS Cbs +/+ mice and examined correlation of insulin signaling genes with tissue Hcy, SAH levels and SAM/SAH ratio. We found negative correlation of Insulin/PI3K signaling genes with Hcy and SAH levels and positive correlation of Insulin/PI3K signaling genes with SAM/SAH ratio. These results led us to hypothesize that HHcy might negatively regulate insulin signaling and further contributes to IR. We found that HHcy impaired glucose metabolism (p<0.01 vs controls [CT]) and insulin sensitivity (p<0.05 vs CT) in Tg-hCBS Cbs -/- mice compared to their littermate controls (Tg-hCBS Cbs -/+ or +/+ mice). Furthermore, HHcy impaired insulin-induced vasorelaxation (31% vs CT, p<0.05) and endothelium-dependent relaxation (26% vs CT, p<0.05) in Tg-hCBS Cbs -/- mouse mesenteric arterioles. HHcy did not affect endothelium-independent relaxation and potassium chloride (KCl) & phenylephrine (PE)-induced contraction responses. Moreover, we found that HHcy significantly inhibited insulin-stimulated Akt and eNOS phosphorylation and activation in HAEC, mesenteric arterial tree, and in aorta. Pre-treatment of mesenteric arterioles with Wortmanin (PI3K inhibitor) and L-NAME (Nitric oxide synthase inhibitor) significantly inhibited insulin-induced vasorelaxation in controls (p<0.05 vs vehicle pre-treatment) but not in Tg-hCBS Cbs -/- mice, suggesting that HHcy impairs insulin-induced PI3K/Akt/eNOS signaling pathway. Moreover, we found that HHcy augmented insulin-induced MAPK pathway in HAEC, mesenteric arteries, and in aorta. In addition, pre-treatment of mesenteric arterioles with MEK inhibitor (PD98059) and endothelin-1A receptor blocker (BQ123) significantly improved (p<0.05 vs vehicle pre-treatment) insulin-induced vasorelaxation in Tg-hCBS Cbs -/- mice. Further analysis of upstream insulin signaling genes show that HHcy downregulated insulin receptor substrates (IRS) 1/2 mRNAs and protein expression but did not affect insulin receptor mRNA…

Advisors/Committee Members: Wang, Hong;, Yang, Xiao-Feng, Ashby, Barrie, Scalia, Rosario, Liu, Ming-Lin, Song, Wenchao;.

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Pansuria, M. (2013). EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,228447

Chicago Manual of Style (16^th Edition):

Pansuria, Meghanaben. “EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.” 2013. Doctoral Dissertation, Temple University. Accessed December 15, 2019. http://digital.library.temple.edu/u?/p245801coll10,228447.

MLA Handbook (7^th Edition):

Pansuria, Meghanaben. “EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.” 2013. Web. 15 Dec 2019.

Vancouver:

Pansuria M. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2019 Dec 15]. Available from: http://digital.library.temple.edu/u?/p245801coll10,228447.

Council of Science Editors:

Pansuria M. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,228447

The Ohio State University

3. Mazumder, Sarmistha. Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death.

Degree: MS, Pharmacy, 2010, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1292203189

► Background: Sudden cardiac death (SCD) is the most common cause of death in the United States and in most developed countries, accounting for ~… (more)

▼ Background: Sudden cardiac death (SCD) is the most common cause of death in the United States and in most developed countries, accounting for ~ 50% of total mortality. The most common underlying cause of SCD is “ventricular fibrillation” (VF). Several clinical trials have reported conflicting results on the benefits of omega-3 fatty acids for the prevention of lethal ventricular arrhythmias following infarction. The explanation for these inconsistent results remains to be determined. Methods: Dogs with healed left ventricular anterior wall myocardial infarctions (MI, 3-4 weeks post- MI, n = 76) were subjected to an exercise and ischemia test to stratify animals by arrhythmia risk as VF susceptible, VF+ (n = 46) and VF resistant, VF- (n = 30). The animals were then assigned to omega-3 fatty acid ethyl esters (1-4 grams/day, n = 45) or corn-oil treatment (placebo, n = 31) for 3 months. Following treatment, arrhythmia inducibility was re-evaluated with the exercise and ischemia test. The left ventricular myocytes were isolated one week following the exercise plus ischemia test. Five age matched dogs served as controls (non-infarcted). Action potentials were recorded by perforated whole cell patch clamp studies (T= 36 ± 0.5°C) to measure the resting membrane potentials (RMP) and the action potential duration at 90% repolarization (APD90). Results: Omega-3 treatment resulted in either sudden death or a positive exercise plus ischemia test in 5 out of 15 (33.3%) VF resistant dogs (p<0.05 vs. placebo) whereas, 4 out of 30 (13.3%) omega-3 treated VF+ dogs no longer had VF at the end of the treatment period (p>0.05 vs. placebo). In addition, 5 out of 30 (16.7%) omega-3 treated dogs VF+ had SCD (p>0.05 vs. placebo). There was no significant differences in RMP following omega-3 treatment in both VF+ and VF- animals (p>0.05 vs. placebo). The APD90 of myocytes of dogs protected from VF following omega-3 treatment was significantly shorter (p<0.05) compared to the myocytes from placebo-treated dogs and was similar to the APD90 from the myocytes of normal control (non-infarcted) dogs at both 0.5 Hz and 1 Hz stimulation frequency. The longest APD90 was observed in myocytes from VF- that developed arrhythmias after omega-3 treatment [VF(-,+)] compared to the myocytes from placebo-treated VF- or normal control animals at both 0.5 Hz and 1 Hz frequency. The prolongation of APD90 in the placebo-treated VF+ group was also associated with a significant (p<0.05 vs. control) increase in beat-to-beat variability of APD90 (quantified as SD1 and SD2), a marker of increased risk of pro-arrhythmia which was normalized after omega-3 treatment (p<0.05). There were no significant differences in the SD1 and SD2 between the placebo-treated VF- animals and control (non-infarcted) animals (p>0.05) whereas the myocytes from VF- dogs that developed arrhythmias after treatment [VF (-,+)] exhibited increased beat-to to-beat variability of APD90 than myocytes from placebo-treated VF- or normal control dogs (p<0.05). Conclusion:… Advisors/Committee Members: Carnes, Cynthia (Advisor).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Mazumder, S. (2010). Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1292203189

Chicago Manual of Style (16^th Edition):

Mazumder, Sarmistha. “Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death.” 2010. Masters Thesis, The Ohio State University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1292203189.

MLA Handbook (7^th Edition):

Mazumder, Sarmistha. “Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death.” 2010. Web. 15 Dec 2019.

Vancouver:

Mazumder S. Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death. [Internet] [Masters thesis]. The Ohio State University; 2010. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1292203189.

Council of Science Editors:

Mazumder S. Effect of omega-3 fatty acids on ventricular action potentials in a canine model of sudden cardiac death. [Masters Thesis]. The Ohio State University; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1292203189

The Ohio State University

4. Ma, Yihui. DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012.

Degree: PhD, Pharmacy, 2011, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1315497619

► FTY720 is a novel immunomodulator that has been approved by FDA for the treatment of relapsing Multiple sclerosis (MS). It features a unique mechanism… (more)

▼ FTY720 is a novel immunomodulator that has been approved by FDA for the treatment of relapsing Multiple sclerosis (MS). It features a unique mechanism of action by reducing circulating levels of naïve lymphocytes by increasing their localization and sequestration in secondary lymphoid organs. It binds several S1P receptors and subsequently induces their internalization and intracellular partial degradation. This blocks the signal that is necessary for egress of lymphocytes from thymus and peripheral lymphoid organs and therefore induces lymphopenia. Recently, FTY720 was found to exhibit anticancer activities in various types of cancers through different signaling pathways independent of S1P1 signaling. For example, our laboratory found that FTY720 induced apoptosis in HCC cells through ROS-PKCd-caspase-3 signaling axis. Taken together, this prompted us to initiate modifications on FTY720 to develop more potent anticancer agents devoid of immunosuppressive activity. OSU-2S, one of the FTY720 derivatives shows most potent cell viability suppression activity in four HCC cell lines. It was derived from FTY720 by replacing the pro-(S)-hydoxymethyl of FTY720 with a propyl group, therefore abrogating the immunosuppressive activity. On the other hand, the anticancer activity was increased by one fold compared to FTY720. Mechanistically, OSU-2S induced hepatocellular carcinoma cells to undergo caspase-3 dependent apoptosis in the same manner as that of FTY720 but at lower concentration. OSU-DY-7 is another derivative that shows high potency in lymphocytic leukemia and primacy B cells purified from chronic lymphocytic leukemia patients. Molecular mechanism studies demonstrate that OSU-DY-7 down regulated the expression level of BIRC5 through transcriptional mechanism by activating MAPK p38. BIRC5 is a cell survival factor and its down regulation may contribute to the cell death. Over all, two anticancer agents, OSU-2S and OSU-DY-7 were developed from FTY720 and they showed strong anticancer activity in HCC cells and lymphocytic leukemia cells respectively through distinct mechanisms of action. PAK1 is a serine/threonine kinase that was the first PAK member identified to be downstream effectors of small GTPase Cdc42 and Rac and regulates cell motility and cytoskeleton. PAK1 was also found to be implicated in a wide range of cellular process, such as cell proliferation and apoptosis rendering it an attractive therapeutic target. In this study, we report on the development of a potent and/or selective PAK1 inhibitors based on a novel PDK1 inhibitor OSU-03012, which also inhibits PAK1 directly. The results show that compound YM-4 and YM-15 demonstrate stronger PAK1 inhibitory activity in a ATP-competitive manner, and more importantly, are much less effective in inhibiting PDK1 kinase activity, even though they are not specific PAK1inhibitor. Advisors/Committee Members: Ching-Shih, Chen (Advisor).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Ma, Y. (2011). DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1315497619

Chicago Manual of Style (16^th Edition):

Ma, Yihui. “DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012.” 2011. Doctoral Dissertation, The Ohio State University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1315497619.

MLA Handbook (7^th Edition):

Ma, Yihui. “DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012.” 2011. Web. 15 Dec 2019.

Vancouver:

Ma Y. DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012. [Internet] [Doctoral dissertation]. The Ohio State University; 2011. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1315497619.

Council of Science Editors:

Ma Y. DEVELOPMENT OF ANTICANCER AGENTS BY MODIFICATION OF A NOVEL IMMUNOSUPPRESSANT FTY720 AND PDK1 INHIBITOR OSU-03012. [Doctoral Dissertation]. The Ohio State University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1315497619

Case Western Reserve University

5. Johnson, William Marshall. The Role of Redox Enzymes in Parkinson’s Disease.

Degree: PhD, Pharmacology, 2016, Case Western Reserve University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1449154708

► Parkinson’s disease (PD) results from the selective loss of dopaminergic neurons in the substantia nigra region of the brain. Although the etiology of PD is… (more)

▼ Parkinson’s disease (PD) results from the selective loss of dopaminergic neurons in the substantia nigra region of the brain. Although the etiology of PD is incompletely understood, genetic mutations including those occurring in LRRK2 and PARK7/DJ-1 are thought to play a significant role in the development of a subset of PD. Because of this genetic component, PD can be classified into two categories: sporadic and familial depending on if the disease is thought to be caused by unknown or genetic factors, respectively. Regardless of the classification, dysregulation of redox homeostasis has been implicated in the pathogenesis of PD. The goal of this work was to investigate the neuroprotective roles ¬¬of two redox enzymes, glutaredoxin 1 (Grx1) and DJ-1 in models of PD in vivo. Post mortem PD and control midbrain sections were subjected to Western blot and immunohistochemical analysis which revealed that dopaminergic neurons in the PD cases investigated contained significantly diminished levels of Grx1. Using C. elegans as a model system it was found that the homologue to Grx1, GLRX-10, mediated dopaminergic neuronal protection via its catalytic activity against LRRK2 toxicity in vivo. Furthermore, genetic ablation of GLRX-10 exacerbated PD phenotypes in C. elegans models of both sporadic and familial PD. Investigation into the protective role of Grx1 revealed that Grx1 regulates DJ-1 protein content in the midbrains of mice. Additionally, DJ-1 levels in cells were found to be diminished by agents that induce S-glutathionylation; DJ-1 was found to be glutathionylated in vivo, and isolated DJ-1 is preferentially glutathionylated at two distinct cysteine residues. Finally, overexpression of DJ-1 was able to partially compensate for a lack of the Grx1 homologue in a C. elegans model of PD. Overall, these analyses indicate that Grx1 plays a critical role in mediating dopaminergic neuronal survival in vivo, likely in part through the regulation of DJ-1; and Grx1 represents a potential target for therapeutic intervention. Advisors/Committee Members: Sabo, Shasta (Committee Chair), Wilson-Delfosse, Amy (Advisor), Mieyal, John (Advisor).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Johnson, W. M. (2016). The Role of Redox Enzymes in Parkinson’s Disease. (Doctoral Dissertation). Case Western Reserve University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1449154708

Chicago Manual of Style (16^th Edition):

Johnson, William Marshall. “The Role of Redox Enzymes in Parkinson’s Disease.” 2016. Doctoral Dissertation, Case Western Reserve University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1449154708.

MLA Handbook (7^th Edition):

Johnson, William Marshall. “The Role of Redox Enzymes in Parkinson’s Disease.” 2016. Web. 15 Dec 2019.

Vancouver:

Johnson WM. The Role of Redox Enzymes in Parkinson’s Disease. [Internet] [Doctoral dissertation]. Case Western Reserve University; 2016. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1449154708.

Council of Science Editors:

Johnson WM. The Role of Redox Enzymes in Parkinson’s Disease. [Doctoral Dissertation]. Case Western Reserve University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1449154708

University of Toledo Health Science Campus

6. Saternos, Hannah C. Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia.

Degree: MSP, Pharmaceutical Sciences (Pharmacology/Toxicology), 2017, University of Toledo Health Science Campus

URL: http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

► Primary endothelial cilia are mechanosensory organelles that are projected into the lumen of blood vessels. Defects in cilia assembly or function can lead to multiple… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Saternos, H. C. (2017). Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia. (Masters Thesis). University of Toledo Health Science Campus. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

Chicago Manual of Style (16^th Edition):

Saternos, Hannah C. “Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia.” 2017. Masters Thesis, University of Toledo Health Science Campus. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731.

MLA Handbook (7^th Edition):

Saternos, Hannah C. “Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia.” 2017. Web. 15 Dec 2019.

Vancouver:

Saternos HC. Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia. [Internet] [Masters thesis]. University of Toledo Health Science Campus; 2017. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731.

Council of Science Editors:

Saternos HC. Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia. [Masters Thesis]. University of Toledo Health Science Campus; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

Case Western Reserve University

7. Rymut, Sharon Marie. Microtubule Regulation in Cystic Fibrosis Pathophysiology.

Degree: PhD, Pharmacology, 2015, Case Western Reserve University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1432730616

► Cystic fibrosis (CF)-related inflammation remains an obstacle in CF treatment and a leading cause for lung disease as the mechanism underlying inflammation is not well… (more)

▼ Cystic fibrosis (CF)-related inflammation remains an obstacle in CF treatment and a leading cause for lung disease as the mechanism underlying inflammation is not well understood. It has been established that CF systems consist of a loss of endosomal transport exemplified by perinuclear cholesterol accumulation, contributing to altered signaling and pro-inflammatory events. It is hypothesized that microtubule stability as analyzed through a decrease in microtubule acetylation and microtubule polymerization rates contribute to the loss of endosomal transport and increased inflammation.One potential contributing factor to these transport issues is the scaffolding protein ßarr2. Studies show that ßarr2 is upregulated due to disrupted microtubule structures, consequence of dysfunctional CFTR and not due to its assumed role in down-regulation of adrenergic receptors. These findings led to the discovery that microtubule acetylation is decreased in CF cells and tissues. Reestablishment of microtubule acetylation through HDAC6 inhibition revealed the reversal of downstream CF phenotypes, including perinuclear cholesterol accumulation, increased RhoA expression, and NF-¿B activation. Additional characterization of HDAC6 inhibition in ¿F508 mice (¿F508/HDAC6) confirmed the pivotal role of microtubule acetylation levels on CF phenotypes, including RhoA expression, growth regulation (height and weight), survival, and response to bacterial challenge. Further investigation of microtubule regulation revealed that microtubule dynamics of CF epithelial cells are also compromised. Both cultured and primary human nasal epithelial (HNE) cells have decreased microtubule polymerization rates due to dysfunctional CFTR. To reestablish microtubule polymerization rates, exchange protein activated by cAMP (EPAC1) was investigated because of its known modulation of microtubule dynamics and its responsiveness to cAMP. Earlier work from the Kelley lab ties EPAC1 to cAMP control of cholesterol accumulation. It was determined that activation of EPAC1 is sufficient to correct microtubule polymerization rates, restore transport, and normalize signaling. These studies established that microtubule stability and dynamics are compromised in CF epithelial cells as a direct consequence of dysfunctional CFTR and their improper modulation contributes to pro-inflammatory profiles. By being able to target microtubule stability through HDAC6 and consequently impacting on inflammatory and other signaling pathways, this work enhances the knowledge of CF pathophysiology and the future of CF therapeutics. Advisors/Committee Members: MacDonald, Paul (Committee Chair), Kelley, Thomas (Advisor).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Rymut, S. M. (2015). Microtubule Regulation in Cystic Fibrosis Pathophysiology. (Doctoral Dissertation). Case Western Reserve University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1432730616

Chicago Manual of Style (16^th Edition):

Rymut, Sharon Marie. “Microtubule Regulation in Cystic Fibrosis Pathophysiology.” 2015. Doctoral Dissertation, Case Western Reserve University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1432730616.

MLA Handbook (7^th Edition):

Rymut, Sharon Marie. “Microtubule Regulation in Cystic Fibrosis Pathophysiology.” 2015. Web. 15 Dec 2019.

Vancouver:

Rymut SM. Microtubule Regulation in Cystic Fibrosis Pathophysiology. [Internet] [Doctoral dissertation]. Case Western Reserve University; 2015. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1432730616.

Council of Science Editors:

Rymut SM. Microtubule Regulation in Cystic Fibrosis Pathophysiology. [Doctoral Dissertation]. Case Western Reserve University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1432730616

The Ohio State University

8. Kang, Chen. ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION.

Degree: PhD, Pharmacy, 2015, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171

► Ischemic heart disease is one of the leading causes for death in the whole world. It has been the top one killer. In general, ischemic… (more)

▼ Ischemic heart disease is one of the leading causes for death in the whole world. It has been the top one killer. In general, ischemic heart disease results from the blockage of the arteries so the blockage in the arteries reduces the supply of blood to the heart muscle causing severe consequences such as heart attack. Treatment for ischemic heart disease involves improving blood flow to the heart muscle. Treatment may include medications, a procedure to open blocked arteries or bypass surgery. Until now, scientists are still looking for more effective ways to reduce the damage to the heart from ischemic heart disease. Cardiac cells preserve a variety of mechanisms in order to protect them from myocardial ischemia. In 1986, Murry and colleagues found out that repeated short episodes of sub-lethal ischemia protected the myocardium against a subsequent lethal ischemic insult which is defined as ischemic preconditioning (IPC). IPC is a powerful form of endogenous protection against myocardial infarction, which has been demonstrated in several animal species and, recently, in isolated human cardiomyocytes. In addition to IPC and its powerful role in cardioprotection, there are numerous other signalings and effectors contributing to the cardioprotection against ischemia. One of them is TASK1 channel, which stabilizes resting membrane potential especially during cardiac ischemia/hypoxia because disruption of ion homestasis eventually causes cell death.Activation of protein kinase C (PKC) via adenosine receptors is known to be involved in the cardioprotection of ischemic preconditioning. Speci¿cally, activated PKCe translocates to mitochondria is thought to be critical of cardioprotection. However, it is still elusive how PKCe translocates to mitochondria. The present study was designed to determine how activation of adenosine receptor induces translocation of PKCe to mitochondria and whether this translocation is age-dependent (Chapter 2). In addition, the two-pore domain potassium channel TASK1 is strongly expressed in the heart and has been shown to regulate the resting membrane potential and action potential. Modulation of the TASK1 background currents provides a mechanism for control of cellular excitability. However, little is known about the localization and regulation of TASK1 in the heart especially whether TASK1 is modulated by caveolar microdomain – one of the most abundant microstructure in cardiac cells. So the following study was designed to determine whether TASK1 is modulated by caveolin-3 (Cav-3) via association with Cav-3 (Chapter 3). We were further interest in whether TASK1 channels play protective role in myocardial hypoxia. We were trying to investigate the molecular mechanisms by which hypoxia regulates TASK1 channels (Chapter 4).In conclusion, we demonstrate that adenosine-induced translocation of PKCe to mitochondria is mediated by caveolin-3-dependent PKC signaling and this process is age-related, possibly through regulation of HSP90 and TOM70 expression. Moreover, our study indicates that TASK1… Advisors/Committee Members: Hu, Keli (Advisor).

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kang, C. (2015). ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171

Chicago Manual of Style (16^th Edition):

Kang, Chen. “ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION.” 2015. Doctoral Dissertation, The Ohio State University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171.

MLA Handbook (7^th Edition):

Kang, Chen. “ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION.” 2015. Web. 15 Dec 2019.

Vancouver:

Kang C. ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION. [Internet] [Doctoral dissertation]. The Ohio State University; 2015. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171.

Council of Science Editors:

Kang C. ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION. [Doctoral Dissertation]. The Ohio State University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171

UCLA

9. Cohen, Alexa Nichelle. Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate.

Degree: Molecular and Medical Pharmacology, 2015, UCLA

URL: http://www.escholarship.org/uc/item/37p2f58x

► Prostatic adenocarcinomas can recur with aggressive and lethal small cell neuroendocrine carcinoma (SCNC). Since glycolysis is a feature of malignancy and the degree generally correlates… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Cohen, A. N. (2015). Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/37p2f58x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cohen, Alexa Nichelle. “Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate.” 2015. Thesis, UCLA. Accessed December 15, 2019. http://www.escholarship.org/uc/item/37p2f58x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cohen, Alexa Nichelle. “Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate.” 2015. Web. 15 Dec 2019.

Vancouver:

Cohen AN. Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate. [Internet] [Thesis]. UCLA; 2015. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/37p2f58x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cohen AN. Glucose Metabolism and CD44 in Small Cell Neuroendocrine Carcinoma of the Prostate. [Thesis]. UCLA; 2015. Available from: http://www.escholarship.org/uc/item/37p2f58x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

10. Zhang, Jin. The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function.

Degree: Pharmacology, 2016, UCLA

URL: http://www.escholarship.org/uc/item/5qr271m5

► BKCa channels are widely expressed ion channels and characterized by their large conductance to potassium and sensitivity to calcium and voltage. It is typically observed… (more)

▼ BKCa channels are widely expressed ion channels and characterized by their large conductance to potassium and sensitivity to calcium and voltage. It is typically observed at the plasma membrane in the majority of cell types, with adult cardiomyocytes being an exception. Previously, both electrophysiological and immunological studies have detected BKCa channels in cardiomyocytes mitoplasts, confirming the presence of this K+ channel (mitoBKCa); however, its physiological functions have not yet fully understood. This work is the first one to examine the interactome of mitoBKCa channels in adult heart (isolated cardiomyocytes and whole ventricle). We used a directed proteomic approach aided by co-immunoprecipitation with BKCa antibodies and pull-down with recombinant DEC sequences. As a result, we identified an extensive network of the mitoBKCa, channel and overall, a total of 1079 different proteins were identified as partners of the BKCa channel in cardiomyocytes and left ventricle, including 151 mitochondrial proteins. Two putative protein partners were selected to validate and further examine the associations with BKCa channels: i) the Tom22 from the mitochondrial import system, and ii) the adenine nucleotide translocator (ANT), which is linked to oxidative phosphorylation and the regulation of mPTP.We first demonstrated the interactions of mitoBKCa with Tom22 through reciprocal co-immunoprecipitation (CO-IP), and then further confirmed that both Tom22 and BKCa were targeted into mitochondria through cell fractionation. This result raises the possibility of the functional interaction between the two proteins in mitochondria, supporting a potential import mechanism of BKCa channel through Tom22. Additionally, we identified the transmembrane domain of BKCa channel (1-711) as the main interacting regions with Tom22 through CO-IP. Next, we verified and studied the interactions between mitoBKCa and ANT with similar approaches. As a result, mitoBKCa was able to co-immunoprecipitate ANT, and the presence of DEC sequence in BKCa-DEC enhanced the ability of ANT to associate with BKCa by ~30%. More importantly, this interaction has a very high likelihood to happen in the mitochondria, as supported by the cell fractionation experiment that the majority of ANT and a considerate amount of mitoBKCa were targeted into mitochondria. This finding indicates a molecular link between mitoBKCa and mPTP, as ANT acts like an important regulatory component of it. Furthermore, the transmembrane domain of BKCa (1-343) can also contribute to the molecular interaction between BKCa channel and ANT.

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, J. (2016). The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/5qr271m5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Jin. “The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function.” 2016. Thesis, UCLA. Accessed December 15, 2019. http://www.escholarship.org/uc/item/5qr271m5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Jin. “The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function.” 2016. Web. 15 Dec 2019.

Vancouver:

Zhang J. The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function. [Internet] [Thesis]. UCLA; 2016. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/5qr271m5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang J. The subproteome of mitoBKCa channels from cardiomyocytes reveals novel insights into its mitochondrial import mechanism and function. [Thesis]. UCLA; 2016. Available from: http://www.escholarship.org/uc/item/5qr271m5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego

11. Yu, Olivia. GPCR and RhoA-Mediated Transcriptional Regulation.

Degree: Biomedical Sciences, 2016, University of California – San Diego

URL: http://www.escholarship.org/uc/item/98d4j5cs

► The ability of a subset of G-protein coupled receptors (GPCRs) to activate RhoAendows them with unique growth regulatory properties. Dysregulation of steps in thissignaling process… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Yu, O. (2016). GPCR and RhoA-Mediated Transcriptional Regulation. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/98d4j5cs

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yu, Olivia. “GPCR and RhoA-Mediated Transcriptional Regulation.” 2016. Thesis, University of California – San Diego. Accessed December 15, 2019. http://www.escholarship.org/uc/item/98d4j5cs.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yu, Olivia. “GPCR and RhoA-Mediated Transcriptional Regulation.” 2016. Web. 15 Dec 2019.

Vancouver:

Yu O. GPCR and RhoA-Mediated Transcriptional Regulation. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/98d4j5cs.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yu O. GPCR and RhoA-Mediated Transcriptional Regulation. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/98d4j5cs

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Irvine

12. Gellner, Candice Ann. Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents.

Degree: Pharmacological Sciences with a concentration in Pharmacology Ph, 2017, University of California – Irvine

URL: http://www.escholarship.org/uc/item/18b1c9fc

► Cigarette smoking is the leading preventable cause of death in the United States. Of those who smoke, 9 out of 10 report trying their first… (more)

▼ Cigarette smoking is the leading preventable cause of death in the United States. Of those who smoke, 9 out of 10 report trying their first cigarette before the age of 18. Although most people who initiate tobacco use are teenagers, animal models for studying tobacco dependence have traditionally focused on how adult animals initiate, withdrawal from and relapse to cigarette smoking. Furthermore, cigarette smoke contains more than 7,000 constituents, including nicotine, yet pre-clinical research has focused on nicotine alone. Our lab began studying these constituents by creating cigarette smoke extract, CSE, a solution which contains the aqueous constituents present in cigarette smoke. Previous work from our lab found that CSE is more potent than nicotine alone and can enhance stress-induced reinstatement in adult male rats. In order to understand how the presence of tobacco smoke constituents may affect adolescents, I investigated the role of these constituents in models of smoking initiation and relapse. I found that the tobacco smoke constituents did not influence adolescent or adult acquisition of self-administration. Adolescents self-administered more low-dose nicotine than adults when their increased non-specific responding was corrected for. During reinstatement of drug seeking, I found that CSE enhanced stress- + cue-induced reinstatement of drug-seeking behavior with no effect of age. To investigate the role of tobacco smoke constituents on attenuation of adolescent self-administration, a novel smoking cessation pharmacotherapy, AT-1001, which is a selective α3β4 nAChR functional antagonist, was used. AT-1001 attenuated both CSE and nicotine self-administration in adolescent rats to a similar degree. My results suggest that both age and the presence of tobacco smoke constituents are important factors in establishing a proper model of tobacco dependence. Furthermore, my findings provide novel insights on adolescent initiation and relapse and offer an exciting potential for the development of a new tobacco dependence animal model that could help create innovative therapeutics to curb the addiction faced by many.

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Gellner, C. A. (2017). Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/18b1c9fc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gellner, Candice Ann. “Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents.” 2017. Thesis, University of California – Irvine. Accessed December 15, 2019. http://www.escholarship.org/uc/item/18b1c9fc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gellner, Candice Ann. “Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents.” 2017. Web. 15 Dec 2019.

Vancouver:

Gellner CA. Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents. [Internet] [Thesis]. University of California – Irvine; 2017. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/18b1c9fc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gellner CA. Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents. [Thesis]. University of California – Irvine; 2017. Available from: http://www.escholarship.org/uc/item/18b1c9fc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

13. Thosani, Niyati Mehta. ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function.

Degree: Molecular and Medical Pharmacology, 2015, UCLA

URL: http://www.escholarship.org/uc/item/8kd0v8cm

► Objective: We previously reported that Hemopexin (Hx), an acute phase protein and a heme scavenger, is significantly increased and associated with proinflammatory HDL under atherogenic… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Thosani, N. M. (2015). ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/8kd0v8cm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Thosani, Niyati Mehta. “ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function.” 2015. Thesis, UCLA. Accessed December 15, 2019. http://www.escholarship.org/uc/item/8kd0v8cm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Thosani, Niyati Mehta. “ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function.” 2015. Web. 15 Dec 2019.

Vancouver:

Thosani NM. ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function. [Internet] [Thesis]. UCLA; 2015. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/8kd0v8cm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Thosani NM. ApoE-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function. [Thesis]. UCLA; 2015. Available from: http://www.escholarship.org/uc/item/8kd0v8cm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

14. Johnson, Tremylla. Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis.

Degree: Molecular and Medical Pharmacology, 2017, UCLA

URL: http://www.escholarship.org/uc/item/9g02d15m

► Propionibacterium acnes is a dominant human skin commensal. It has been implicated in acne pathogenesis, but its role remains unclear. Recent metagenomic studies have revealed… (more)

▼ Propionibacterium acnes is a dominant human skin commensal. It has been implicated in acne pathogenesis, but its role remains unclear. Recent metagenomic studies have revealed that certain P. acnes strains are highly associated with acne, while some others are associated with healthy skin. Little information exists about P. acnes strain-level differences beyond the genomic differences. In this study, I revealed that acne-associated type IA P. acnes strains produced significantly higher levels of porphyrins (a metabolite important in acne development) than health-associated strains (type II). Strains of type IA-1 and type IA-2 produced similar levels of porphyrins. Moreover, porphyrin production in these P. acnes strains is modulated by vitamin B12. On the other hand, health-associated type II strains produced low levels of porphyrins and did not respond to vitamin B12. Strains from other lineages (type IB and type III) have lower levels of porphyrin production and porphyrin levels were not modulated by vitamin B12. Using small molecule substrates and inhibitors, I demonstrated that porphyrin biosynthesis was modulated at the metabolic level in type IA strains. By comparing the porphyrin operons of different strains, I identified a repressor gene (deoR) of porphyrin biosynthesis that was encoded in all health-associated P. acnes type II strains, types IB-3, IC, and III strains, but not in acne-associated type IA strains. The expression of deoR suggests regulation of porphyrin production at the transcriptional level in health-associated strains. Other skin propionibacteria, Propionibacterium granulosum, Propionibacterium avidum, and Propionibacterium humerusii, produced little or no porphyrin, and were not regulated by vitamin B12. Additionally, I developed an assay using mass spectrometry to analyze porphyrin levels in skin samples. The findings from my study provide a potential molecular explanation for the different contributions of P. acnes strains to skin health and disease, and support the role of vitamin B12 in acne pathogenesis in a subset of the population. This study emphasizes the importance of understanding the role of the commensal microbial community in health and disease at the strain level, and suggests potential utility of health-associated P. acnes strains in acne treatment.

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Johnson, T. (2017). Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/9g02d15m

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Johnson, Tremylla. “Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis.” 2017. Thesis, UCLA. Accessed December 15, 2019. http://www.escholarship.org/uc/item/9g02d15m.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Johnson, Tremylla. “Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis.” 2017. Web. 15 Dec 2019.

Vancouver:

Johnson T. Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis. [Internet] [Thesis]. UCLA; 2017. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/9g02d15m.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Johnson T. Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis. [Thesis]. UCLA; 2017. Available from: http://www.escholarship.org/uc/item/9g02d15m

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Irvine

15. Park, John. Mechanisms of Thrombospondin-4 in Pain Modulation.

Degree: Pharmacology and Toxicology, 2014, University of California – Irvine

URL: http://www.escholarship.org/uc/item/2496030f

► Upregulation of the thrombospondin-4 (TSP4) or calcium channel alpha-2-delta-1 subunit (Cava2d1) in the dorsal spinal cord and dorsal root ganglia plays a causal role in… (more)

▼ Upregulation of the thrombospondin-4 (TSP4) or calcium channel alpha-2-delta-1 subunit (Cava2d1) in the dorsal spinal cord and dorsal root ganglia plays a causal role in neuropathic pain development through an unidentified mechanism. TSP4 blockade either by antibodies or inactivation of the TSP4 gene prevents development of chronic pain states. Intrathecal injection of TSP4 proteins into naive rats can cause dorsal horn neuron hyperexcitability and allodynia, which are blocked by the Cava2d1 ligand gabapentin. These findings suggest that TSP4 and Cava2d1 may interact together in mediating pain processing. Here, I show that TSP4 binding to Cava2d1 is detectable in the same immunocomplexes from rodent spinal cords and in solid-phase binding. SPOT Peptide array analysis and in vitro binding of TSP4 recombinant truncation proteins to Cava2d1 reveal multiple binding sites within the TSP4 Epidermal Growth Factor-like domains (EGF-like) and coil-coil domain. Functionally, lumbar intrathecal injection of EGF-like domain proteins is sufficient to induce behavioral hypersensitivity. Selective ablation of Cava2d1 from Nav1.8-positive sensory neurons abolishes EGF-like domain induced thermal hyperalgesia, but not tactile allodynia. A 15-mer TSP4 peptide from the EGF-like domains can block both Cava2d1- and TSP4-induced behavioral hypersensitivity, presumably by disrupting the interaction between TSP4 and Cava2d1. My data suggest that the EGF-like domains of TSP4 interact with Cava2d1 to induce chronic pain states in a modality specific manner. Emerging data also suggest that Cava2d1 and TSP4 interact to induce synapse formation. To determine if maladaptive changes in synapses correlate with neuropathic pain states in a nerve injury model with injury-induced upregulation of TSP4 and Cava2d1, I examined synapse numbers at ultrastructure level in superficial dorsal horn of rats after trigeminal nerve injury. I found a significant increase in both excitatory and inhibitory synapses within lamina I and II of the superficial dorsal horn, respectively, and a decrease in mean synaptic length, a marker for synapse strength, of inhibitory interneurons mainly in lamina I of the injury side. Together, it is likely that injury-induced TSP4/Cava2d1 contribute to the development of chronic pain states after nerve injury through a mechanism involving dysregulation of excitatory and inhibitory synapses in the superficial dorsal horn.

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Park, J. (2014). Mechanisms of Thrombospondin-4 in Pain Modulation. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/2496030f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Park, John. “Mechanisms of Thrombospondin-4 in Pain Modulation.” 2014. Thesis, University of California – Irvine. Accessed December 15, 2019. http://www.escholarship.org/uc/item/2496030f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Park, John. “Mechanisms of Thrombospondin-4 in Pain Modulation.” 2014. Web. 15 Dec 2019.

Vancouver:

Park J. Mechanisms of Thrombospondin-4 in Pain Modulation. [Internet] [Thesis]. University of California – Irvine; 2014. [cited 2019 Dec 15]. Available from: http://www.escholarship.org/uc/item/2496030f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Park J. Mechanisms of Thrombospondin-4 in Pain Modulation. [Thesis]. University of California – Irvine; 2014. Available from: http://www.escholarship.org/uc/item/2496030f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Case Western Reserve University

16. Fox, Tara L. Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery.

Degree: PhD, Pharmacology, 2016, Case Western Reserve University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

► Polymeric nanoparticles have shown promise in addressing issues surrounding poor solubility of hydrophobic drugs, helping to facilitate dispersion of drug molecules throughout the body. This… (more)

▼ Polymeric nanoparticles have shown promise in addressing issues surrounding poor solubility of hydrophobic drugs, helping to facilitate dispersion of drug molecules throughout the body. This work describes the characterization of a novel class of polymeric nanoparticles, mixed brush-grafted nanoparticles, for drug delivery. Mixed poly(acrylic acid) (PAA)/polystyrene (PS) brush-grafted silica nanoparticles are directly visualized by cryoelectron microscopy (cryoEM) in organic and aqueous solvents. These amphiphilic nanoparticles are predicted to be environmentally responsive and adopt distinct morphologies in different solvent environments. The morphology of mixed PAA/PS brush-grafted particles has been studied previously in a dried state but never in a solvent environment. CryoEM allows imaging the sample in a frozen solvated state at the resolution of a transmission electron microscope. Cryoelectron tomograms (cryoET) were generated for PAA/PS nanoparticles in both N,N-dimethylformamide (DMF, a nonselective good solvent) and water (a selective solvent for PAA). Different morphologies were observed in these two solvents. In DMF, mixed PAA/PS brushes are observed to form laterally separated bundles, whereas in water PAA chains form a near-complete shell, shielding collapsed PS chains that form surface-tethered micelles against the silica core. These cryoET results confirm the predicted environmentally responsive nature of PAA/PS mixed brush-grafted nanoparticles. These structural findings suggested a possible loading and release mechanism for hydrophobic compounds, which was tested in loading and release experiments with two hydrophobic fluorescent dyes, Nile Red and Nile Blue. Of these two compounds, Nile Blue is retained the best and released in a slow release phase with a half-life of ~13 days. The hydrophobic dye-loading capability of mixed brush-grafted nanoparticles with varying percentages of PS was also compared. The results indicate that a high percentage of hydrophobic PS is required for retention of Nile Blue. Finally, Nile Blue-loaded mixed brush-grafted nanoparticles were shown to mediate delivery of dye to HeLa cells. Altogether, these experiments represent the initial characterization of mixed brush-grafted nanoparticles for drug delivery applications. Advisors/Committee Members: Stewart, Phoebe L. (Advisor), Mears, Jason (Committee Chair).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Fox, T. L. (2016). Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery. (Doctoral Dissertation). Case Western Reserve University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

Chicago Manual of Style (16^th Edition):

Fox, Tara L. “Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery.” 2016. Doctoral Dissertation, Case Western Reserve University. Accessed December 15, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789.

MLA Handbook (7^th Edition):

Fox, Tara L. “Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery.” 2016. Web. 15 Dec 2019.

Vancouver:

Fox TL. Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery. [Internet] [Doctoral dissertation]. Case Western Reserve University; 2016. [cited 2019 Dec 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789.

Council of Science Editors:

Fox TL. Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery. [Doctoral Dissertation]. Case Western Reserve University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

University of Kansas

17. Gong, Chen. Iron regulation and heat shock proteins in ischemic stroke.

Degree: MS, Pharmacology & Toxicology, 2016, University of Kansas

URL: http://hdl.handle.net/1808/25736

► Ischemic stroke is one of the leading causes of brain injury and death. Many mechanisms underlying ischemia-induced neuronal death have been investigated. Dysregulation of brain… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Gong, C. (2016). Iron regulation and heat shock proteins in ischemic stroke. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/25736

Chicago Manual of Style (16^th Edition):

Gong, Chen. “Iron regulation and heat shock proteins in ischemic stroke.” 2016. Masters Thesis, University of Kansas. Accessed December 15, 2019. http://hdl.handle.net/1808/25736.

MLA Handbook (7^th Edition):

Gong, Chen. “Iron regulation and heat shock proteins in ischemic stroke.” 2016. Web. 15 Dec 2019.

Vancouver:

Gong C. Iron regulation and heat shock proteins in ischemic stroke. [Internet] [Masters thesis]. University of Kansas; 2016. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/1808/25736.

Council of Science Editors:

Gong C. Iron regulation and heat shock proteins in ischemic stroke. [Masters Thesis]. University of Kansas; 2016. Available from: http://hdl.handle.net/1808/25736

Boston University

18. Hai, Jerry. Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats.

Degree: MS, Medical Sciences, 2017, Boston University

URL: http://hdl.handle.net/2144/23780

► BACKGROUND: Hypertension is a major health concern with a myriad of possible causes. Sodium is a major component of blood pressure regulation implicated in the… (more)

▼ BACKGROUND: Hypertension is a major health concern with a myriad of possible causes. Sodium is a major component of blood pressure regulation implicated in the maintenance of fluid volume. The blood pressure response to changes in salt intake varies considerably among individuals; salt-sensitive individuals exhibit increases in blood pressure parallel to elevated sodium intake, whereas salt-resistant individuals maintain constant blood pressure regardless of variations in sodium intake. Salt-Sensitive Hypertension (SSH) develops due to an impairment of normal mechanisms that react to an elevated sodium load. Aging is another major risk factor for the development of hypertension. The effects of aging have a profound impact on the cardiovascular, renal, and nervous systems, which work together to regulate blood pressure. The development of SSH and impact of aging on blood pressure have been well-established, but the neurophysiological mechanisms implicated in SSH and aging, have only been recently explored. OBJECTIVE: To provide mechanistic insight regarding the integrated roles of the renal and nervous systems in age-dependent hypertension in male Sprague-Dawley (SD) rats. METHODS: Male SD rats of various ages were randomly assigned to various experimental protocols. 3-month-old male SD rats were randomly assigned to receive Renal-Capsaicin surgery (Renal-CAP) to ablate the afferent renal nerve (ARN) or sham surgery, followed by an acute 5% body weight i.v.-isotonic volume expansion protocol (5%-VE) in which natriuretic response and cardiovascular functions (HR/MAP) were continuously monitored and analyzed for the duration of the experimental period. 3/8/16-month-old male SD rats without Renal-CAP surgery were similarly exposed to the 5%-VE protocol. C-fos immunohistochemistry (c-Fos IHC) was performed on brain slides prepared from rats assigned to the 5%-VE protocol to assess PVN parvocellular neuronal activation, as a marker for ARN activity. 3/8/16-month-old male SD rats on normal-salt and high-salt (NS/HS; 0.6%/4% sodium chloride respectively) diets were assigned to an amiloride and hydrochlorothiazide protocol (AM-HCTZ) to evaluate NCC activity, and exposed to i.p. hexamethonium to account for the sympathetic contribution to blood pressure. Renal/plasma NE content was assessed via ELISA to further account for sympathetic tone. Immunoblotting was performed on 3-month-old control saline-infused, s.c.-norepinephrine (NE), and s.c.-norepinephrine+terazosin/propranolol male SD rats to assess NCC, phosphorylated NCC (pNCCT58), SPAK, WNK1, OxSR1, and phosphorylated OxSR1 protein levels, to evaluate the roles of the α1/β-adrenoceptors in the NCC-implicated ARN-mediated sympathoinhibitory pathway. RESULTS: In response to the 5%-VE protocol, the natriuretic response was attenuated in Renal-Cap rats. Renal-CAP rats also experienced a significant increase in MAP in response to 5%-VE, while sham Renal-CAP rats did not. Both Renal-CAP and sham Renal-CAP rats experienced a significant increase in the mean number of PVN…

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Hai, J. (2017). Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/23780

Chicago Manual of Style (16^th Edition):

Hai, Jerry. “Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats.” 2017. Masters Thesis, Boston University. Accessed December 15, 2019. http://hdl.handle.net/2144/23780.

MLA Handbook (7^th Edition):

Hai, Jerry. “Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats.” 2017. Web. 15 Dec 2019.

Vancouver:

Hai J. Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats. [Internet] [Masters thesis]. Boston University; 2017. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2144/23780.

Council of Science Editors:

Hai J. Pathophysiology of age-dependent hypertension in male Sprague-Dawley rats. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/23780

Boston University

19. Mauricio, Ian Paolo Morelos. Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway.

Degree: MS, Medical Sciences, 2018, Boston University

URL: http://hdl.handle.net/2144/31243

► The Hippo tumor suppressor pathway is a highly conserved signaling cascade initially identified in Drosophila which acts to regulate organ size and cellular proliferation. The… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Mauricio, I. P. M. (2018). Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/31243

Chicago Manual of Style (16^th Edition):

Mauricio, Ian Paolo Morelos. “Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway.” 2018. Masters Thesis, Boston University. Accessed December 15, 2019. http://hdl.handle.net/2144/31243.

MLA Handbook (7^th Edition):

Mauricio, Ian Paolo Morelos. “Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway.” 2018. Web. 15 Dec 2019.

Vancouver:

Mauricio IPM. Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway. [Internet] [Masters thesis]. Boston University; 2018. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2144/31243.

Council of Science Editors:

Mauricio IPM. Defining the role of the kinase MST4 in the context of the Hippo tumor suppressor pathway. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/31243

Boston University

20. Helfand, Alexander. 3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans.

Degree: MS, Medical Sciences, 2014, Boston University

URL: http://hdl.handle.net/2144/14328

► 3,4-Methylenedioxymethamphetamine (MDMA) is a ring-substituted amphetamine with a potential for abuse. Although originally developed by Merck, MDMA is an illegal drug that is popular recreationally,… (more)

▼ 3,4-Methylenedioxymethamphetamine (MDMA) is a ring-substituted amphetamine with a potential for abuse. Although originally developed by Merck, MDMA is an illegal drug that is popular recreationally, and is more recently being touted as a therapeutic agent. Unlike some other drugs in the amphetamine class, the mechanism(s) by which MDMA produces its subjective effects are not well understood. MDMA is a selective serotonin (5-HT) neurotoxin. Exposure to MDMA can lead to lasting reductions in brain 5-HT and 5-HT axonal markers. Somewhat paradoxically, its acute pharmacological effects involve a dramatic acute increase in serotonin (and other monoamine) levels in the brain and the periphery. MDMA is also a direct agonist at several different monoaminergic receptors. Although these pharmacological properties of MDMA are known, they don't appear to fully explain the subjective of effects of MDMA, which include feelings of well-being and euphoria. One unfortunate notion held by many MDMA users is that the drug is safe, or at least safer than many other illegal drugs. This is a notion that is strengthened by MDMA's current and past use as a psychotherapeutic agent, although definitive safety/efficacy reports have yet to appear in the literature. In recent years, there has been a renewed push to acknowledge the potential utility of MDMA in the treatment of conditions such as post-traumatic stress disorder. MDMA has been reported to damage a number of organ systems in addition to its properties as a selective 5-HT neurotoxin in the brain. Furthermore, recreational MDMA users develop tolerance, which results in a need to increase the dose to achieve the same subjective effects, thereby also increasing the risk for dose-related adverse effects. A number of research laboratories have demonstrated that abstinent MDMA users develop both a loss of brain 5-HT markers, in addition to potential functional consequences of 5-HT neurotoxicity, including deficits in cognitive function, endocrine modulation, and sleep regulation. Although these effects have been well-described, the mechanism by which MDMA leads to neurotoxicity remains unclear, and multiple theories have been suggested. There are many unanswered questions when it comes to MDMA. Without knowing more about how MDMA acts in the body and how it produces toxicities, use of the drug constitutes a significant risk. Not only are the acute, systemic and potentially fatal effects of MDMA problematic, but longer term functional consequences secondary to serotonin depletion may pose significant problems for abstinent MDMA users as they age. In light of the drug's popularity, the need for answers and increased public awareness has never been more pressing. Although MDMA is classified by the Drug Enforcement Agency (DEA) as schedule I, popular musicians have begun to positively reference MDMA in their lyrics, which has likely contributed to the observed rise in MDMA-related hospital visits and fatalities. Communities, parents, and healthcare professionals must make a more…

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Helfand, A. (2014). 3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/14328

Chicago Manual of Style (16^th Edition):

Helfand, Alexander. “3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans.” 2014. Masters Thesis, Boston University. Accessed December 15, 2019. http://hdl.handle.net/2144/14328.

MLA Handbook (7^th Edition):

Helfand, Alexander. “3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans.” 2014. Web. 15 Dec 2019.

Vancouver:

Helfand A. 3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans. [Internet] [Masters thesis]. Boston University; 2014. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2144/14328.

Council of Science Editors:

Helfand A. 3,4-methylenedioxymethamphetamine (MDMA): pharmacology, toxicology, usage patterns, and neurological effects in humans. [Masters Thesis]. Boston University; 2014. Available from: http://hdl.handle.net/2144/14328

Boston University

21. Kim, Andrew. Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption.

Degree: 2015, Boston University

URL: http://hdl.handle.net/2144/16268

► Alcoholism results from an interaction between genetic and environmental factors. However, the neurobiological mechanisms mediating the propensity to consume excessive amounts of alcohol are still… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Kim, A. (2015). Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption. (Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16268

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kim, Andrew. “Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption.” 2015. Thesis, Boston University. Accessed December 15, 2019. http://hdl.handle.net/2144/16268.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kim, Andrew. “Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption.” 2015. Web. 15 Dec 2019.

Vancouver:

Kim A. Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption. [Internet] [Thesis]. Boston University; 2015. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2144/16268.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kim A. Pituitary adenylate cyclase-activating polypeptide regulates excessive alcohol consumption. [Thesis]. Boston University; 2015. Available from: http://hdl.handle.net/2144/16268

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

22. Cacace, Hanna. Alternative opioid-sparing treatment options for acute pain management therapy.

Degree: MS, Medical Sciences, 2018, Boston University

URL: http://hdl.handle.net/2144/31158

► The vast array of causes, mechanisms, and interventional strategies for pain has created an extensive field of research spanning a variety of disciplines. This thesis… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Cacace, H. (2018). Alternative opioid-sparing treatment options for acute pain management therapy. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/31158

Chicago Manual of Style (16^th Edition):

Cacace, Hanna. “Alternative opioid-sparing treatment options for acute pain management therapy.” 2018. Masters Thesis, Boston University. Accessed December 15, 2019. http://hdl.handle.net/2144/31158.

MLA Handbook (7^th Edition):

Cacace, Hanna. “Alternative opioid-sparing treatment options for acute pain management therapy.” 2018. Web. 15 Dec 2019.

Vancouver:

Cacace H. Alternative opioid-sparing treatment options for acute pain management therapy. [Internet] [Masters thesis]. Boston University; 2018. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2144/31158.

Council of Science Editors:

Cacace H. Alternative opioid-sparing treatment options for acute pain management therapy. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/31158

Stellenbosch University

23. Fasinu, Pius Sedowhe. In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential.

Degree: PhD, Medicine, 2013, Stellenbosch University

URL: http://hdl.handle.net/10019.1/85850

► ENGLISH ABSTRACT: Introduction Earlier studies have shown the popularity of herbal products among people as traditional, complementary or alternative medication. One of the major clinical… (more)

▼ ENGLISH ABSTRACT: Introduction Earlier studies have shown the popularity of herbal products among people as traditional, complementary or alternative medication. One of the major clinical risks in the concomitant administration of herbal products and prescription medicine is pharmacokinetic herb-drug interaction (HDI). This is brought about by the ability of phytochemicals to inhibit or induce the activity of metabolic enzymes and transport proteins. The aim of this study was to investigate the potential of the crude extracts of popular medicinal herbs used in South Africa to inhibit major cytochrome P450 (CYP) enzymes and transport proteins through in vitro assessment. Methods Medicinal herbs were obtained from traditional medical practitioners and 15 were selected for this study. The selected herbal products were extracted and incubated with human liver microsomes to monitor the following reactions as markers for the metabolic activities of the respective CYP: phenacetin O-deethylation (CYP1A2), diclofenac 4‟-hydroxylation (CYP2C9), S-mephenytoin 4‟- hydroxylation (CYP2C19) and testosterone 6β-hydroxylation (CYP3A4). In addition, the influence of Lessertia frutescens (formerly Sutherlandia frutescens) and Hypoxis hemerocallidea was investigated on more isozymes: coumarin 7-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), paclitaxel 6α-hydroxylation (CYP2C8), bufuralol 1‟-hydroxylation (CYP2D6), chlorzoxazone 6- hydroxylation (CYP2E1) and midazolam 1‟-hydroxylation (CYP3A4/5). The generation of the CYPspecific substrates/metabolites were monitored and quantified with the aid of LC-MS/MS. The metabolic clearance of midazolam using cryopreserved hepatocytes was monitored in the presence of Lessertia frutescens and Hypoxis hemerocallidea. The potential of both to inhibit human ATP-binding cassette (ABC) transporter activity was assessed using recombinant MDCKII and LLC-PK1 cells overexpressing human breast cancer resistant protein (BCRP) and human P-glycoprotein (P-gp), respectively. Similarly, the potential for interactions with human organic anion transporting polypeptide (OATP1B1 and OATP1B3) was assessed using recombinant HEK293 cells over-expressing OATP1B1 and OATP1B3, respectively. Results Bowiea volubilis, Kedrostis Africana, Chenopodium album, Lessertia frutescens (methanolic extract), Hypoxis hemerocallidea, Spirostachys africana and Lessertia frutescens (aqueous extract), in ascending order of potency demonstrated strong inhibition of CYP1A2 activity (IC50 = 1-100 g/mL). Similarly, Emex australis, Alepidea amatymbica, Pachycarpus concolor, Lessertia frutescens, Capparis sepiaria, Kedrostis africana and Pentanisia prunelloides inhibited CYP2C9 with IC50 less than 100 g/mL. The following demonstrated strong inhibition of CYP2C19 with IC50 values less than 100 g/mL: Acacia karroo, Capparis sepiaria, Chenopodium album, Pachycarpus concolor, Ranunculus multifidus, Lessertia frutescens and Zantedeschia aethiopica. CYP3A4 was inhibited by Lessertia frutescens, Hypoxis… Advisors/Committee Members: Rosenkranz, Bernd, Bouic, Patrick J., Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology..

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fasinu, P. S. (2013). In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/85850

Chicago Manual of Style (16^th Edition):

Fasinu, Pius Sedowhe. “In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential.” 2013. Doctoral Dissertation, Stellenbosch University. Accessed December 15, 2019. http://hdl.handle.net/10019.1/85850.

MLA Handbook (7^th Edition):

Fasinu, Pius Sedowhe. “In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential.” 2013. Web. 15 Dec 2019.

Vancouver:

Fasinu PS. In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential. [Internet] [Doctoral dissertation]. Stellenbosch University; 2013. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/10019.1/85850.

Council of Science Editors:

Fasinu PS. In vitro assessment of some traditional medications used in South Africa for pharmacokinetics drug interaction potential. [Doctoral Dissertation]. Stellenbosch University; 2013. Available from: http://hdl.handle.net/10019.1/85850

Stellenbosch University

24. De Kock, Lizanne. Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment.

Degree: MSc in Medical Science, Medicine, 2013, Stellenbosch University

URL: http://hdl.handle.net/10019.1/85726

► ENGLISH ABSTRACT: Background: Para-aminosalicylic acid (PAS) is one of the first effective anti-tuberculosis agents and has become one of the principal second-line drugs to treat… (more)

▼ ENGLISH ABSTRACT: Background: Para-aminosalicylic acid (PAS) is one of the first effective anti-tuberculosis agents and has become one of the principal second-line drugs to treat patients with an extended resistance spectrum. Despite being one of the oldest anti-tuberculosis drugs, little data is available regarding its pharmacokinetics, drug interactions, genetic factors and dosing regimens, especially for the relative new granular slow release PAS (GSR-PAS) preparation. Objectives The aim of the study was to investigate the pharmacokinetics, tolerability and safety of a single 8 g once- or 4 g twice-daily GSR-PAS dose in a multidrug- or extensively drug resistant tuberculosis (M/XDR-TB) population, in which some subjects were also co-infected with the human immunodeficiency virus (HIV). An additional objective was to investigate the potential covariates (i.e. genetic factors and drug interactions) that can alter the pharmacokinetics of PAS. Study design and methodology A randomised, two-period, open-label cross-over study was conducted in 32 adults (≥18 years old) with M/XDR-TB admitted at Brooklyn Chest Hospital, Cape Town, South Africa and treated for drug resistant tuberculosis with a multidrug regimen containing GSR-PAS. The subjects were randomised to follow a single 8 g once-daily GSR-PAS regimen or a 4 g twice-daily GSR-PAS regimen for 8 days. On the eighth day blood samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12 and 24 hours. After the 24-hour sample (Day 9) the regimens were crossed-over. The tolerability and safety of the two regimens were determined using Visual Analogue Scales and interviews. PAS plasma concentrations were determined by a developed HPLC-MS/MS method. N-acetyltransferase (NAT1 and NAT2) genotyping was performed. The data of this study together with unpublished data of a previous study in a very similar population were used in a pharmacometric analysis to determine the PK parameters and any subject covariates. Results and Discussion In comparison to the 4 g twice-daily GSR-PAS dose, the single 8 g once-daily GSR-PAS dose generated a pharmacokinetic profile with a significantly higher maximum concentration (Cmax), concentration at 12 hours (C12) and area under the curve 0 to 12 hours (AUC12). The concentrations of all subjects on the twice-daily regimen were maintained above a minimum inhibitory concentration (MIC) throughout a 12-hour interval, while the single 8 g dose was able to sustain the PAS plasma concentrations above the MIC in 18 out of 29 subjects (62.1%) for the entire 24-hour dosing interval. Both regimens were reasonably well tolerated but most subjects preferred the twice-daily dosing. The clearance of PAS was increased by 45% in HIV positive subjects prescribed antiretroviral treatment (ART), possibly due to interaction with efavirenz (EFV). No significant associations were found for any of the individual NAT1 or NAT2 genotypes, but a difference between mean concentrations of the different genotypic groups was reported. Conclusions The 8 g once-daily dose has the… Advisors/Committee Members: Rosenkranz, B., Diacon, A. H., Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Clinical Pharmacology..

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

De Kock, L. (2013). Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/85726

Chicago Manual of Style (16^th Edition):

De Kock, Lizanne. “Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment.” 2013. Masters Thesis, Stellenbosch University. Accessed December 15, 2019. http://hdl.handle.net/10019.1/85726.

MLA Handbook (7^th Edition):

De Kock, Lizanne. “Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment.” 2013. Web. 15 Dec 2019.

Vancouver:

De Kock L. Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment. [Internet] [Masters thesis]. Stellenbosch University; 2013. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/10019.1/85726.

Council of Science Editors:

De Kock L. Pharmacokinetics of twice-daily versus once-daily dosing with granular slow-release para-aminosalicylic acid in adults on second-line anti-tuberculosis and antiretroviral treatment. [Masters Thesis]. Stellenbosch University; 2013. Available from: http://hdl.handle.net/10019.1/85726

University of Cape Town

25. Gabriels, Gary Anthony. The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration.

Degree: Image, Division of Clinical Pharmacology, 2013, University of Cape Town

URL: http://hdl.handle.net/11427/3281

► Nutritional supplements are used by competitive and recreational athletes of all ages. As a consequence the supplement industry has grown to meet the increasing demand.… (more)

▼ Nutritional supplements are used by competitive and recreational athletes of all ages. As a consequence the supplement industry has grown to meet the increasing demand. The regulation of the supplement industry is unrefined, which increases the risk of the nutritional supplements being contaminated. Contamination may be intentional, where the companies “spike” their products with an ergogenic aid, or unintentional. A consequence of contamination is that an athlete may fail a drug test after ingesting a contaminated supplement or there may be negative health consequences. Without adequate legislation it is difficult to control the industry and reduce the risk of contamination in the supplement. Objectives: To investigate the industry associated with commercially available nutritional and traditional supplements. These are in the five specific areas; (i) to review the regulations and legislations, and labelling and claims associated with nutritional products in the USA, European Union and South Africa, (ii) to assess the labelling and claims information on nutritional supplement products imported into and manufactured or assembled in South Africa, (iii) to assess using a survey questionnaire the container labelling and other sources of information that assist consumers of nutritional products in their purchasing decisions, (iv) to assess traditional commercial supplements for contamination and consistency of trace elements and heavy metals using Inductively Coupled Plasma-Mass Spectrometry, and (v) to assess the content of nutritional commercial supplements for steroids, stimulants and other compounds of interest using Tandem Liquid Chromatography-Mass Spectrometry.Methods: The thesis is divided into 6 Chapters. Chapter 1 describes the background to the problem and Chapter 2 reviews the existing legislation. In Chapter 3 the labelling and claims information on 40 nutritional supplements products are analysed, and the self-administered questionnaire determined what product label and other information influences consumers of nutritional supplements in their purchasing decisions. In Chapter 4 the consistency of trace elements and heavy metals are analysed in selected nutritional supplements using Inductively Coupled Plasma Mass Spectrometry. In Chapter 5 selected nutritional supplements are analysed for steroids, stimulants and other compounds using Tandem Liquid Chromatography Mass Spectrometry. All the data of these sections are summarised in Chapter 6. Advisors/Committee Members: Lambert, Mike (advisor), Smith, Peter (advisor).

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Gabriels, G. A. (2013). The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/3281

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gabriels, Gary Anthony. “The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration.” 2013. Thesis, University of Cape Town. Accessed December 15, 2019. http://hdl.handle.net/11427/3281.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gabriels, Gary Anthony. “The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration.” 2013. Web. 15 Dec 2019.

Vancouver:

Gabriels GA. The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration. [Internet] [Thesis]. University of Cape Town; 2013. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/11427/3281.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gabriels GA. The investigation and assessment of Nutritional and Traditional Supplement products for content validity, contamination and adulteration. [Thesis]. University of Cape Town; 2013. Available from: http://hdl.handle.net/11427/3281

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Wayne State University

26. Baidwan, Sartaj S. Metformin, Glucotoxicity And Islet Dysfunction.

Degree: MS, Pharmaceutical Sciences, 2017, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_theses/548

► METFROMIN, GLUCOTOXICITY AND ISLET DYSFUNCTION by SARTAJ BAIDWAN MAY 2017 Advisor: Dr. Anjaneyulu Kowluru Major: Pharmaceutical Sciences Degree: Master of Science Glucotoxicity is the… (more)

▼ METFROMIN, GLUCOTOXICITY AND ISLET DYSFUNCTION by SARTAJ BAIDWAN MAY 2017 Advisor: Dr. Anjaneyulu Kowluru Major: Pharmaceutical Sciences Degree: Master of Science Glucotoxicity is the leading cause for β-cell dysfunction [e.g., defective glucose-stimulated insulin secretion] in Type 2 Diabetes [T2DM]. Recent studies from our lab have shown sustained Rac1 activation leading to the activation of downstream signaling steps including stress kinase [p53, p38MAPK] activation and mitochondrial dysregulation [caspase-3 activation] in pancreatic islet beta-cells exposed to glucotoxic [HG] conditions [20 mM; 24 hrs]. Metformin [MF] is an oral anti-diabetic drug that is being widely prescribed to T2DM. MF works by suppressing hepatic glucose production and increasing glucose uptake by the target tissues. However, potential beneficial effects of MF on pancreatic beta-cell dysfunction under HG conditions have not been studied to date. Therefore, in the current studies, we asked if MF [0-30 μM; clinically relevant concentrations] affords protective effects against HG-induced metabolic dysfunction of the pancreatic beta [INS-1 832/13] cells. Since recent studies from our laboratory have demonstrated activation of Rac1, a small G-protein, as an upstream signaling event to stress kinase activation, we asked if protective effects of MF may, in part, be due to inhibition of HG-induced Rac1 activation in INS-1 832/13 cells. Data from these studies have suggested nearly 40% inhibition in HG-induced Rac1 activation [3.43±0.57 fold over basal; n=4; p<0.05] by MF. Evidence is also presented to highlight novel roles for sustained activation of Rac1 in HG-induced expression of Cluster of Differentiation 36 [CD36], a fatty acid transporter protein, which is implicated in cell apoptosis. Western blot analysis indicated a significant increase in the phosphorylation of p38MAPK [2.31±0.21 fold over basal; n=5; p<0.05], JNK1/2 and phosphorylation of p53 [4.42±1.20 fold over basal; n=3; p<0.05] in INS-1 832/13 cells. MF [15µM] markedly attenuated HG-induced p38MAPK [74.8%], JNK 1 and p53 [55.7%] activation under these experimental conditions. Our data from Bax phosphorylation [an indicator of cell dysregulation] studies demonstrated an increase in the phosphorylation of two Bax isoforms [Baxα by 1.63± 0.04 fold over basal; n=3; p<0.05; and Baxβ by 1.32±0.11 over basal; n=3; p<0.05]. MF [30µM] attenuated the phosphorylation of only Baxα isoform [by 77.3%]. Lastly, our data also suggested that co-provision of MF significantly reduced [72.4%] HG-induced caspase-3 activation. Together, these findings suggest significant protection by MF against HG-induced metabolic defects [activation of Rac1-stress kinase-caspase-3 signaling module] in the islet beta-cell. Potential implications of these findings in the context of novel and direct regulation of islet β-cell function by metformin are discussed. Advisors/Committee Members: Anjaneyulu Kowluru.

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Baidwan, S. S. (2017). Metformin, Glucotoxicity And Islet Dysfunction. (Masters Thesis). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_theses/548

Chicago Manual of Style (16^th Edition):

Baidwan, Sartaj S. “Metformin, Glucotoxicity And Islet Dysfunction.” 2017. Masters Thesis, Wayne State University. Accessed December 15, 2019. https://digitalcommons.wayne.edu/oa_theses/548.

MLA Handbook (7^th Edition):

Baidwan, Sartaj S. “Metformin, Glucotoxicity And Islet Dysfunction.” 2017. Web. 15 Dec 2019.

Vancouver:

Baidwan SS. Metformin, Glucotoxicity And Islet Dysfunction. [Internet] [Masters thesis]. Wayne State University; 2017. [cited 2019 Dec 15]. Available from: https://digitalcommons.wayne.edu/oa_theses/548.

Council of Science Editors:

Baidwan SS. Metformin, Glucotoxicity And Islet Dysfunction. [Masters Thesis]. Wayne State University; 2017. Available from: https://digitalcommons.wayne.edu/oa_theses/548

University of Kansas

27. Zhang, Yuchen. IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3.

Degree: PhD, Pharmacology, Toxicology & Therapeutics, 2017, University of Kansas

URL: http://hdl.handle.net/1808/27333

► Many transporters are expressed at the basolateral membrane of human hepatocytes, including Organic Anion Transporting Polypeptide 1B1 (OATP1B1), OATP1B3, Organic Cation Transporter 1 (OCT1), Na+/Taurocholate… (more)

▼ Many transporters are expressed at the basolateral membrane of human hepatocytes, including Organic Anion Transporting Polypeptide 1B1 (OATP1B1), OATP1B3, Organic Cation Transporter 1 (OCT1), Na+/Taurocholate Cotransporting Polypeptide (NTCP) and more. These transporters are part of the absorption system of the liver, which is responsible for the uptake of chemicals from the portal vein into hepatocytes for further metabolism and elimination. Extensive studies have characterized the function of these transporters, and results suggest that liver uptake transporters, like OATP1B3 and OATP1B1, or OATP1B3 and NTCP, have many overlapping substrates. Because these transporters seem to play an essential role in the protection of the body from xenobiotics, it is important to better understand their function and how they interact with each other. In this dissertation, I focused on one of these transporter, OATP1B3, as a model transporter to improve the understanding of liver uptake transporters. OATP1B3 is responsible for the uptake of many endogenous compounds like bile acids and hormones as well as xenobiotics, including numerous drugs. Recent studies demonstrated that some of the liver uptake transporters like OATP1B1, OCT1 and NTCP can form homo-oligomers. In the first specific aim, I evaluated the hypothesis that OATP1B3 also can form homo-oligomers. To address this aim, co-immunoprecipitation and proximity ligation assays of differently tagged OATP1B3 were performed in transiently transfected HEK293 cells. The results demonstrated that OATP1B3 indeed can form homo-oligomers. In addition, uptake assays with wild-type and non-functional OATP1B3 suggested that the OATP1B3 unit in the homo-oligomers works as individual functional unit. Besides that, by using proximity ligation assays, the interaction between OATP1B3 and OATP1B1, and between OATP1B3 and NTCP was demonstrated in HEK293 cells. Interactions between OATP1B3 and NTCP were also confirmed in frozen liver sections. In the second specific aim, I evaluated the hypothesis that OATP1B3 can form hetero-oligomers with other transporters and that these interactions can influence their expression and function. I was able to extend the findings of hetero-oligomerization to include OCT1 using both immunoprecipitation and proximity ligation assays. Uptake assays and surface biotinylation experiments were performed with HEK293 cells co-expressing OATP1B3 and OCT1, OATP1B3 and OATP1B1, or OATP1B3 and NTCP. The results demonstrated that these interactions between OATP1B3 and the other transporters lead to changes in both, function and expression of OATP1B3 in a transporter-dependent manner. In the third specific aim, I evaluated the hypothesis that photoaffinity labeling can be used to study the binding sites and translocation pathways of OATP1B3. The known OATP1B3 substrate 8-fluorescein-cAMP (8-FcA) was used to perform photoaffinity labeling experiments with CHO Flp-In cells stably expressing His-tagged OATP1B3. The results suggested that 8-FcA can label proteins but background… Advisors/Committee Members: Hagenbuch, Bruno A (advisor), Blanco, V. Gustavo (cmtemember), Kasturi, Partha (cmtemember), Lampe, Jed N (cmtemember), Reed, Gregory A (cmtemember).

Subjects/Keywords: Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, Y. (2017). IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/27333

Chicago Manual of Style (16^th Edition):

Zhang, Yuchen. “IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3.” 2017. Doctoral Dissertation, University of Kansas. Accessed December 15, 2019. http://hdl.handle.net/1808/27333.

MLA Handbook (7^th Edition):

Zhang, Yuchen. “IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3.” 2017. Web. 15 Dec 2019.

Vancouver:

Zhang Y. IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3. [Internet] [Doctoral dissertation]. University of Kansas; 2017. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/1808/27333.

Council of Science Editors:

Zhang Y. IDENTIFICATION AND CHARACTERIZATION OF THE OLIGOMERIZATION AND STRUCTURAL FUNCTIONAL RELATIONSHIP OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3. [Doctoral Dissertation]. University of Kansas; 2017. Available from: http://hdl.handle.net/1808/27333

University of Cape Town

28. Amlabu, Veronica Asibi. Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children.

Degree: Image, Division of Clinical Pharmacology, 2013, University of Cape Town

URL: http://hdl.handle.net/11427/3307

► The World Health Organization recommends the use of isoniazid preventive therapy to reduce the incidence of tuberculosis disease in populations at risk for developing the… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Amlabu, V. A. (2013). Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/3307

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Amlabu, Veronica Asibi. “Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children.” 2013. Thesis, University of Cape Town. Accessed December 15, 2019. http://hdl.handle.net/11427/3307.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Amlabu, Veronica Asibi. “Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children.” 2013. Web. 15 Dec 2019.

Vancouver:

Amlabu VA. Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children. [Internet] [Thesis]. University of Cape Town; 2013. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/11427/3307.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Amlabu VA. Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children. [Thesis]. University of Cape Town; 2013. Available from: http://hdl.handle.net/11427/3307

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cape Town

29. Combrinck, Jill Michelle. The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum.

Degree: Image, Division of Clinical Pharmacology, 2016, University of Cape Town

URL: http://hdl.handle.net/11427/22760

► The malaria parasite detoxifies host red blood cell derived haem by conversion into the inert biocrystal haemozoin. Inhibiting this critical pathway is proposed to be… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Combrinck, J. M. (2016). The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/22760

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Combrinck, Jill Michelle. “The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum.” 2016. Thesis, University of Cape Town. Accessed December 15, 2019. http://hdl.handle.net/11427/22760.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Combrinck, Jill Michelle. “The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum.” 2016. Web. 15 Dec 2019.

Vancouver:

Combrinck JM. The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum. [Internet] [Thesis]. University of Cape Town; 2016. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/11427/22760.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Combrinck JM. The role of haem in the mechanism of action of antimalarials in Plasmodium falciparum. [Thesis]. University of Cape Town; 2016. Available from: http://hdl.handle.net/11427/22760

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cape Town

30. Melariri, Paula E. The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria.

Degree: Image, Division of Clinical Pharmacology, 2010, University of Cape Town

URL: http://hdl.handle.net/11427/11552

► In Nigeria most of the populace relies heavily on medicinal plants for the treatment of malaria. This thesis describes the investigation of the antiplasmodial properties… (more)

Subjects/Keywords: Pharmacology

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APA (6^th Edition):

Melariri, P. E. (2010). The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/11552

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Melariri, Paula E. “The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria.” 2010. Thesis, University of Cape Town. Accessed December 15, 2019. http://hdl.handle.net/11427/11552.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Melariri, Paula E. “The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria.” 2010. Web. 15 Dec 2019.

Vancouver:

Melariri PE. The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria. [Internet] [Thesis]. University of Cape Town; 2010. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/11427/11552.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Melariri PE. The therapeutic effectiveness of some local Nigerian plants used in the treatment of malaria. [Thesis]. University of Cape Town; 2010. Available from: http://hdl.handle.net/11427/11552

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations