Skip to content
Home » Scientific Interpretation Open Exam

Scientific Interpretation Open Exam

  • by

Open book exam. The below pages were extracted from a paper published in a reputable journal. Please read them carefully and answer the SIX questions following the extract within this document. You are expected to use all resources available to you to help answer the questions. There is a 300 word limit to questions 1-5 and 600 words to question 6.


Methylglyoxal (MGO) is a metabolite of glucose. Since serum MGO level is increased in diabetic patients, MGO is implicated in diabetic complications related to vascular injury. We have recently demonstrated that glucose metabolite is a more powerful stimulant for endothelial cells (ECs) injury rather than glucose or advanced glycation-end products. Recent clinical trials suggest that angiotensin receptor blockers are effective to prevent diabetes-associated cardiovascular disorders beyond blood pressure lowering effect.

To explore the mechanisms, we examined effects of Telmisartan on MGO- induced ECs injury. Treatment of human umbilical vein ECs with MGO (560 μM) induced time-dependent (0–24 h) cell death. MGO-induced cell death was apoptosis since MGO increased cleaved caspase-3 expression. Telmisartan (0.1– 10 μM) inhibited MGO-induced cell death and caspase-3 activation. These results indicate that Telmisartan prevents MGO-induced apoptosis by inhibiting caspase-3 activation, which might explain at least in part the beneficial effects of Telmisartan against diabetes-related cardiovascular diseases.


Methylglyoxal (MGO) is a metabolite of glucose. MGO is formed from triose phosphates or acetol under hyperglycemic conditions and serves as advanced glycation-end products (AGEs) precursors. Serum concentration of MGO or MGO-derived AGEs is significantly increased in diabetic patients with complications including retinopathy and nephropathy. MGO is further implicated in diabetes-associated cardiovascular diseases including hypertension.

Telmisartan is a selective angiotensin II type 1 receptor (AT1R) blocker. Besides blood pressure lowering effect, large clinical trials revealed that AT1R blockers

such as losartan (LIFE) and candesartan (CHARM) have protective roles against ischemic heart diseases. The most recent clinical trials (ONTARGET) demonstrated that Telmisartan also has preventive roles against ischemic heart diseases in diabetic patients with a similar potency to angiotensin converting enzyme inhibitor. Several studies recently suggest that the effects of Telmisartan are mediated via not only blockade of AT1R but also activation of peroxisome proliferators- activated receptor PPAR-γ.

We recently demonstrated that glyoxal, one of the metabolites of glucose is a more powerful inducer for vascular endothelial cells (ECs) inflammatory injury rather than glucose itself or AGEs. In the present study, we first examined effects of treatment of human vascular ECs with MGO, and next examined whether Telmisartan could affect the MGO-induced ECs injury.


Materials. Reagent sources were methylglyoxal (MGO) solution (Sigma– Aldrich, MO, USA) and Telmisartan (Boehringer Ingelheim, Ingelheim, Germany). Antibody sources were cleaved caspase-3 (Cell Signaling Technology, MA, USA) and total actin (Sigma–Aldrich).
Cell culture. Human umbilical vein ECs (HUVECs) were obtained from Kurabo (Osaka, Japan) and cultured in Medium200 supplemented with low serum growth supplement (LSGS; Cascade Biologics, OR, USA) as described previously. Cells at passages from 4 to 7 were used for experiments. Morphological changes of HUVECs were examined under light microscope (CKX31, Olympus, Tokyo, Japan) equipped with digital camera (SP-350, Olympus)…


  1. Describe briefly the aims of the experiments described in this paper .

(12 Marks)

  • Describe and comment on the data presented in Figure 1, commenting on the stated magnification and the statistical analysis.

(12 Marks)

  • Comment on the Western blot shown in Figure 2A. What are the important criteria for loading controls and their presentation? Also comment on Figure 2B.

(12 Marks)

  • Do you think the concentration of the substances used are applicable to humans? (Serum MGO in diabetes 200nM; maximum Telmisartan serum concentration can be calculated from 80mg as the maximum clinical dose, MW ≈ 500, distribution volume 50l).

(12 Marks)

  • With reference to Figure 4, do you think that Telmisartan would be effective in reducing apoptosis in humans?

(12 Marks)

  • Suggest experiments to test the mechanism of Telmisartan’s actions.

(40 Marks)


error: Content is protected !!