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High glucose (HG) culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells, analogous to any other cell type in our body. It interferes with diverse signaling pathways, i.e. mammalian target of rapamycin (mTOR)-phosphoinositide 3-kinase (PI3K)-Akt signaling, to impact physiological cellular functions, leading to low cell survival and higher cell apoptosis rates. While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells (MSCs), a recent study has shown that HG culture conditions dysregulate mTOR-PI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential (MtMP) that lowers ATP production. This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities. Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG. Some previous studies have also reported altered mitochondrial membrane polarity (causing hyperpolarization) and reduced mitochondrial cell mass, leading to perturbed mitochondrial homeostasis. The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria, altering their bioenergetics and reducing their capacity to produce ATP. These are significant data, as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy. Therefore, MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor survival rates and increased rates of post engraftment proliferation. As hyperglycemia alters the bioenergetics of donor MSCs, rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.
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BACKGROUND: The exact mechanisms for the development of essential hypertension are not known. Activation of the renin-angiotensin-aldosterone system (RAAS) in adipose tissue may represent an important link between obesity and hypertension. This study investigates the effects of oral intake of glucose with and without NaCl on angiotensin II (AngII) and aldosterone in obese and nonobese patients with essential hypertension. METHODS: Twenty newly diagnosed untreated essential hypertensive patients and 15 normotensive control subjects matched for age, gender, and BMI were studied. Participants fasted overnight (8-10 hrs), and then each subject took 75 gm glucose alone and with 3 gm NaCl, each dissolved in 250 ml. Subjects were monitored for 2 hours. Half hourly BP, plasma glucose (PG), serum Na+, K+, insulin, AngII, and aldosterone were measured. Subjects were classified into obese (BMI >30 Kg/m2) (11 patients and 8 control) and nonobese (BMI <30 Kg/m2) (9 patients and 7 control). RESULTS: After intake of glucose with NaCl serum, AngII was significantly higher in obese hypertensive patients compared with nonobese patients (P = 0.016). Intake of glucose with NaCl resulted in a significantly higher serum Na in obese hypertensive patients compared with nonobese patients Na (P = 0.009). Serum aldosterone was significantly higher in obese patients (P = 0.03, after glucose; P = 0.003, after glucose with NaCl) and in nonobese patients (P = 0.000 and P = 0.000, respectively) compared with their respective normotensive control subjects. In obese and nonobese patients, intake of glucose and glucose with NaCl showed no significant change in the levels of serum AngII and aldosterone which was associated a significant increase in serum Na in obese patients (P = 0.03) and a highly significant reduction in serum K in nonobese patients (P = 0.001). CONCLUSION: Failure of suppression or inappropriate maintenance of secretion of AngII and aldosterone in both hypertensive groups by intake of glucose with NaCl may indicate a possible mechanism of essential hypertension.
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BACKGROUND: Lectures are one of the most common teaching methods in medical education. Didactic lectures were perceived by the students as the least effective method. Teaching methods that encourage self-directed learning can be effective in delivering core knowledge leading to increased learning. Problem based learning has been introduced as an active way of learning but it has some obstacles in developing countries where the intake is huge with minimum resources. This study introduces a new teaching approach: lectures based on problems (LBP) and evaluates their effectiveness compared to traditional lectures (TL) in physiology teaching. METHODS: LBP and TL were applied in physiology teaching of medical students at University of Science and Technology during their study of introduction to physiology and respiratory physiology courses. Equal number of lectures was given as LBP and as TL in each course. Students were given quizzes at the end of each course which were used to compare the effectiveness of the two types of lectures. A questionnaire was used to assess students' satisfaction about LBP and the perceived effects of the two methods on the students' attitude and practice towards learning physiology. RESULTS: In LBP the students have better attention (P = 0.002) and more active role (P = 0.003) than in TL. Higher percentage of students think that LBP stimulated them to use references more (P = 0.00006) and to use the lecture time more effectively (P = 0.0001) compared to TL. However, there was no significant difference between LBP and TL in the awareness of the learning objectives. About 64% of students think that LBP is more enjoyable and it improved their understanding of physiology concepts. Comparison of the students' quiz marks showed that the means of the students' marks in the introduction to physiology and respiratory courses were higher in the quizzes of LBP than in TL with a significant difference between them ((P = .000), (P = .006) respectively. CONCLUSIONS: LBP improved students' understanding of physiology concepts and increased students' satisfaction about physiology learning. LBP achieved some of the objectives of PBL with the minimum resources and it can be used to improve the effectiveness of the lectures.
