7 research outputs found
AN ANALYSIS OF IODINE DEFICIENCY DISORDER AND ERADICATION STRATEGIES IN THE HIGH ATLAS MOUNTAINS OF MOROCCO
Food Consumption/Nutrition/Food Safety, Health Economics and Policy,
Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS -generating agents
A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2·− ), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2·− is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2·− and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2·−, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells
An Analysis of Iodine Deficiency Disorder and Eradication Strategies in the High Atlas Mountains of Morocco
The population of the Ounein Valley in the High Atlas Mountains in Morocco is at high risk of iodine deficiency. We investigated local children\u27s iodine deficiency and goiterpattems as well as food consumption habits through a household survey. Median urinary iodine content and goiter analysis both reflect moderate iodine deficiency. Total fish consumption has a statistically significant, positive effect on urinary iodine content. Fish consumption, like that of salt, is closely related to market access. Respondents are uniformly unaware of the dietary etiology of goiter. An effective strategy to reduce the high incidence of iodine deficiency disorder among children in the valley must attend to four crucial issues: fish consumption, salt iodization, nutrition education, and market access
AN ANALYSIS OF IODINE DEFICIENCY DISORDER AND ERADICATION STRATEGIES IN THE HIGH ATLAS MOUNTAINS OF MOROCCO
AN ANALYSIS OF IODINE DEFICIENCY DISORDER AND ERADICATION STRATEGIES IN THE HIGH ATLAS MOUNTAINS OF MOROCCO
The population of the Ounein Valley in the High Atlas Mountains in Morocco is at high risk of iodine deficiency. We investigated local children's iodine deficiency and goiter patterns as well as food consumption habits through a household survey. Median urinary iodine content and goiter analysis both reflect moderate iodine deficiency. Total fish consumption has a statistically significant, positive effect on urinary iodine content. Fish consumption, like that of salt, is closely related to market access. Respondents are uniformly unaware of the dietary etiology of goiter. An effective strategy to reduce the high incidence of iodine deficiency disorder among children in the valley must attend to four crucial issues: fish consumption, salt iodization, nutrition education, and market access