Insulin mimetic effect of D-allulose on apolipoprotein A-I gene.

Several nutrients modulate the transcriptional activity of the apolipoprotein A-I (apo A-I) gene. To determine the influence of rare sugars on apo A-I expression in hepatic (HepG2) and intestinal derived (Caco-2) cell lines, apo A-I, albumin, and SP1 were quantified with enzyme immunoassay and Western blots while mRNA levels were quantified with real-time polymerase chain reaction. The promoter activity was measured using transient transfection assays with plasmids containing various segments and mutations in the promoter. D-allulose and D-tagatose, increased apo A-I concentration in culture media while D-sorbose and D-allose did not have any measurable effects. D-allulose did not increase apo A-I levels in Caco-2 cells. These changes paralleled the increased mRNA levels and promoter activity. D-allulose-response was mapped at the insulin response core element (IRCE). Mutation of the IRCE decreased the ability of D-allulose and insulin to activate the promoter. Treatment of HepG2 cells, but not Caco-2 cells, with D-alluose and insulin increased SP1 expression relative to control cells. D-allulose augmented the expression and IRCE binding of SP1, an essential transcription factor for the insulin on apo A-I promoter activity. D-allulose can modulate some insulin-responsive genes and may have anti-atherogenic properties, in part due to increasing apo A-I production. PRACTICAL APPLICATIONS: Coronary artery disease (CAD) is the number one cause of mortality in industrialized countries. A risk factor associated with CAD is low high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) concentrations in plasma. Thus, novel therapeutic agents or nutrients that upregulate apo A-I production should be identified. D-allulose and D-tagatose are used as sweeteners and may have favorable effects on insulin resistance and diabetes. This study shows that D-allulose and D-tagatose increases apo A-I production through increased transcription factor SP1-binding to insulin response element of the promoter. These sweeteners modulate some insulin responsive genes, increase the production of apo-A-I, and therefore may have anti-atherogenic properties.

Severe recurrent hypoglycaemia in a patient with aggressive melanoma.

We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

Radiofrequency-intravascular ultrasound assessment of lesion coverage after angiography-guided emergent percutaneous coronary intervention in patients with non-ST elevation myocardial infarction.

Using radiofrequency-intravascular ultrasound (VH-IVUS), we have previously demonstrated that in 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention with optimal angiographic result, the stent does not fully cover the whole VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) related to the culprit lesion. Presently, we set out to extend these findings to 20 patients with non-STEMI with Thrombolysis In Myocardial Infarction flow 3 in the infarct-related artery before intervention who were then treated with angiography-guided direct stent implantation. The lesion was imaged with VH-IVUS before and after intervention, but the results were blinded to the operator. Plaque rupture site was identified in 8 lesions (40%), all proximal to the minimum lumen area (MLA) site. The maximum necrotic core site was found proximal to MLA in 18 lesions and at the MLA in 2 lesions. Although the plaque rupture site was fully covered with the stent in all lesions, an uncovered VH-TCFA was found in 7 lesions (35%), 4 in the proximal reference segment, 1 in the distal reference segment, and 2 in both the proximal and distal reference segments. In conclusion, in 35% of patients with non-STEMI undergoing angiography-guided emergent percutaneous coronary intervention, the stent does not fully cover a VH-TCFA related to the culprit lesion.

Virtual histology-intravascular ultrasound assessment of lesion coverage after angiographically-guided stent implantation in patients with ST Elevation myocardial infarction undergoing primary percutaneous coronary intervention.

An occlusion or severe stenosis (angiographic culprit lesion) of the infarct-related artery is frequently located at the site of the maximum thrombus burden, whereas the origin of the plaque rupture (the true culprit) can be situated proximal or distal to it. The aim of this study was to examine stent coverage of true culprit lesions in 20 patients who underwent primary percutaneous coronary intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow restored in the infarct-related artery by angiographically guided direct stenting. Images of lesions were obtained using virtual histology-intravascular ultrasound before and after intervention (blinded to the operator). Plaque rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11 proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the proximal reference segment and in 3 patients in the proximal and distal reference segments. In conclusion, in about 50% of patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with optimal angiographic results, the stent does not fully cover the maximum necrotic core site related to the culprit lesion.

Assessment of culprit plaque temperature by intracoronary thermography appears inconclusive in patients with acute coronary syndromes.

OBJECTIVE: Safety and feasibility evaluation of intracoronary temperature measurements in patients with acute coronary syndromes (ACS) using a catheter based thermography system. METHODS AND RESULTS: Thermography was performed in 40 patients with ACS. A 3.5-F thermography catheter containing 5 thermocouples measuring vessel wall temperature, and 1 thermocouple measuring blood temperature (accuracy 0.05 degrees C) was used. Gradient (deltaTmax) between blood temperature (T(bl)) and the maximum wall temperature during pullback was measured. The device showed satisfactory safety in ACS. Only in 16 patients (40%) deltaTmax was > or = 0.1 degrees C. In 23 patients (57.5%) the highest deltaTmax was found in the culprit segment. DeltaTmax between culprit and adjacent non-culprit segments was observed in patients with transient blood flow interruption during thermography (0.11+/-0.03 versus 0.08+/-0.01; P=0.04), in contrast to patients with preserved flow (0.07+/-0.03 versus 0.06+/-0.02; P=0.058). CONCLUSIONS: The novel, technically sophisticated intracoronary thermography proved its safety and feasibility. However, we were not able to convincingly and consistently differentiate between different lesions at risk, despite a selection of lesions that should appear most distinct to differentiate. A systematic interruption of flow may be necessary to achieve diagnostic results consistently, although such requirement may unfavorably change the risk-to-benefit ratio of this developing technology.

Y-chromosomal STR haplotype analysis reveals surname-associated strata in the East-German population.

In human populations, the correct historical interpretation of a genetic structure is often hampered by an almost inherent inability to differentiate between ancient and more recent influences upon extant gene pools. One method to trace recent population movements is the analysis of surnames, which, at least in Central Europe, can be thought of as traits 'linked' to the Y chromosome. Illegitimacy, extramarital birth and changes of surnames may have substantially obscured this linkage. In order to assess the actual extent of correlation between surnames and Y-chromosomal haplotypes in Central Europe, we typed Y-chromosomal short tandem repeat markers in 419 German males from Halle. These individuals were subdivided into three groups according to the origin of their respective surname, namely German (G), Slavic (S) or 'Mixed' (M). The distribution of the haplotypes was compared by Analysis of Molecular Variance. While the M group was indistinguishable from group G (PhiST=-0.0008, P>0.5), a highly significant difference (PhiST=0.0277, P<0.001) was observed between the S group and the combined G+M group. This surprisingly strong differentiation is comparable to that of European populations of much larger geographic and linguistic difference. In view of the major migration from Slavic countries into Germany in the 19th century, it appears likely that the observed concurrence of Slavic surnames and Y chromosomes is of a recent rather than an early origin. Our results suggest that surnames may provide a simple means to stratify, and thereby to render more efficient, Y-chromosomal analyses of Central Europeans that target more ancient events.