subject:(Vitamin K3)

Queens University

1. Odozor, Chioma. Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia .

Degree: Biomedical and Molecular Sciences, Queens University

URL: http://hdl.handle.net/1974/24249

Despite its negative connotation as a toxic gas, carbon monoxide (CO) is involved in anti-inflammatory, cytoprotective and vasodilatory processes, suggesting a possible therapeutic role in many disease states. Endogenous CO production results in a resting percent carboxyhemoglobin (%COHb) level of 0.5 – 1.5% in humans. In smokers, this can rise to 17%. It has been shown that women who smoke have a lower risk of developing pre-eclampsia (PE), which is thought to be due to an increase in CO. PE is a pregnancy-related disease that is characterized by new-onset hypertension and proteinuria. PE is multifactorial, but a common belief is that poor placentation and systemic maternal endothelial dysfunction are involved in its pathogenesis. Menadione (MD), synthetic vitamin K3, increases CO production in rat brain microsomes. This research tested the hypothesis that MD could also raise CO in the blood and tissue of pregnant mice. A dose-response study was first conducted in non-pregnant mice to determine an efficacious, non-lethal dose. After determining their baseline water consumption rate, non-pregnant CD-1 mice were given one of three doses of MD in drinking water for seven days. No significant differences in %COHb between groups were observed. Splenic CO production and mass doubled in the 4 g/L and 6.5 g/L MD groups, compared to the 1.5 g/L and control cohorts. In a separate experiment, the effect of MD on gestational day (GD) 15 placental tissue CO production was tested using two different tissue preparation methods. Non-linear regression showed that while absolute levels of CO were higher in sonicated placentas than whole placentas, the relative increase in CO between concentrations was the same using either method. Lastly, oral administration of 6.5 g/L MD from GD10.5 – 17.5 significantly decreased maternal weight gain and fetal survival. Significant increases in %COHb and splenic CO were seen in the treatment group on GD17.5, with a positive trend for CO production in the liver, placenta and kidney. Overall, the findings demonstrate that MD can induce CO production in vivo. However, further studies in a mouse model of PE at a safer dose must be done to establish the drug’s therapeutic potential.

Subjects/Keywords: Pre-Eclampsia ; Pregnancy ; Menadione ; Vitamin K3 ; Carbon Monoxide

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

APA (6^th Edition):

Odozor, C. (n.d.). Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/24249

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Odozor, Chioma. “Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia .” Thesis, Queens University. Accessed February 25, 2021. http://hdl.handle.net/1974/24249.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Odozor, Chioma. “Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia .” Web. 25 Feb 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Odozor C. Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia . [Internet] [Thesis]. Queens University; [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1974/24249.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Odozor C. Menadione as a Novel Approach to Increasing Carbon Monoxide Production in Pregnancy: Establishing a Possible Therapeutic Role in Pre-eclampsia . [Thesis]. Queens University; Available from: http://hdl.handle.net/1974/24249

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Toledo Health Science Campus

2. Zahedi, Shadi. Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?.

Degree: MSBS, College of Medicine, 2010, University of Toledo Health Science Campus

URL: http://rave.ohiolink.edu/etdc/view?acc_num=mco1280427079

Gastrointestinal (GI) carcinoids are slow growing malignancies of neuroendocrine phenotype that can behave aggressively. To date, there are no effective therapies for metastatic carcinoid cancer. Previous work by our lab and others has shown that carcinoids express variety of voltage-operated (VOCCs) and non-voltage-operated Ca2+ channels to allow Ca2+ to enter the cell. Although, the role of Ca2+ entry in these tumors is not well understood, previous work by our group and others has shown that mitochondria are important regulators of voltage-operated and non-voltage-operated Ca2+ entry. In addition, cancer cells typically exhibit mitochondrial dysfunction and poor anti-oxidant status. These observations and the central role that mitochondria play in metabolism, Ca2+ homeostasis and cell death pathways make mitochondria an appealing potential target for anti-cancer treatment in carcinoid tumors. We used an spectrum of human cancer cell lines and a variety of microfluorescence methods including wide-field, confocal, and total internal reflection (TIRF) microscopy to assess Ca2+ signaling and mitochondrial function in combination with pharmacological interventions to assay whether mitochondria are a potential target for anti-cancer therapy. To this end, we tested the effectiveness of an oxidant therapy approach in carcinoid cells. Advisors/Committee Members: Giovannucci, David (Committee Chair).

Subjects/Keywords: Biomedical Research; Molecular Biology; Scientific Imaging; carcinoid tumors; mitochondrial; calcium signaling; TIRF microscopy; oxidant therapy; vitamin K3; vitamin C

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

APA (6^th Edition):

Zahedi, S. (2010). Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?. (Masters Thesis). University of Toledo Health Science Campus. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=mco1280427079

Chicago Manual of Style (16^th Edition):

Zahedi, Shadi. “Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?.” 2010. Masters Thesis, University of Toledo Health Science Campus. Accessed February 25, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=mco1280427079.

MLA Handbook (7^th Edition):

Zahedi, Shadi. “Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?.” 2010. Web. 25 Feb 2021.

Vancouver:

Zahedi S. Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?. [Internet] [Masters thesis]. University of Toledo Health Science Campus; 2010. [cited 2021 Feb 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1280427079.

Council of Science Editors:

Zahedi S. Are Mitochondria a Potential Target for Anti-Cancer Therapy in Carcinoid Tumors?. [Masters Thesis]. University of Toledo Health Science Campus; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1280427079

University of Missouri – Columbia

3. Hu, Chunhua. Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2.

Degree: 2007, University of Missouri – Columbia

URL: https://doi.org/10.32469/10355/6270

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Reactive oxygen species (ROS) are produced in cells by enzymic and non-enzymic mechanisms and play important roles in the pathogenesis of neurodegenerative diseases. However, mechanisms for the increase in ROS and their effects leading to altered cell metabolism have not been studied in detail in the central nervous system. In the first series of studies, we examined ROS production in primary rat astrocytes and their downstream effects on changes in signaling cascades and morphology using menadione. ROS production induced by menadione was completely inhibited by NADPH oxidase inhibitors including apocynin and gp91ds-tat. Menadione also stimulated phosphorylation of p38 and ERK, and caused actin polymerization and which can be inhibited by inhibitors for NAPDH oxidase and MAPK. In the second part, we tested the role of cytosolic phospholipase A2 in astrocytes in response to oxidative stress. Menadione increased the immunoreactivity of phospho-cPLA2 and caused plasma membranes to become more gel-like, which were abrogated by down regulating cPLA2 with siRNA. In summary, our study demonstrated the important role of NAPDH oxidase in production of ROS and their link to activation of MAPK pathways and cPLA2 in astrocytes. We further demonstrated that excess production of ROS, such as that mediated by menadione, can alter cell membrane properties, morphology, and cytoskeletal arrangement and in turn cell death mechanism. – From public.pdf Advisors/Committee Members: Sun, Grace Y. (advisor).

Subjects/Keywords: Astrocytes; NAD (Coenzyme); Apoptosis; Cell membranes; Phospholipase A2 – Inhibitors; Cytosol; Oxidative stress; Active oxygen; Astrocytes – physiology; NADPH Oxidase – physiology; Apoptosis – physiology; Cell Membrane; Central Nervous System – physiology; NADP – antagonists & inhibitors; Oxidative Stress – physiology; Phospholipases A – metabolism; Reactive Oxygen Species – metabolism; Vitamin K3

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Hu, C. (2007). Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2. (Thesis). University of Missouri – Columbia. Retrieved from https://doi.org/10.32469/10355/6270

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):

Hu, Chunhua. “Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2.” 2007. Thesis, University of Missouri – Columbia. Accessed February 25, 2021. https://doi.org/10.32469/10355/6270.

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

MLA Handbook (7^th Edition):

Hu, Chunhua. “Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2.” 2007. Web. 25 Feb 2021.

Vancouver:

Hu C. Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2. [Internet] [Thesis]. University of Missouri – Columbia; 2007. [cited 2021 Feb 25]. Available from: https://doi.org/10.32469/10355/6270.

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

Council of Science Editors:

Hu C. Activation of astrocytes: involvement of NADPH oxidase and cytosolic phospholipase A2. [Thesis]. University of Missouri – Columbia; 2007. Available from: https://doi.org/10.32469/10355/6270

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

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