Dimitrios Papazoglou

Hypoxia inducible factor 1α and 2α overexpression in inflammatory bowel disease

Aims: Hypoxia inducible factors 1α and 2α (HIF1α and HIF2α) are hypoxia regulated transcriptional factors, which control the expression of a variety of genes responsible for angiogenesis, glycolysis, and the inhibition of apoptosis. Because angiogenesis and tissue regeneration are integral components of the inflammatory process, this study was designed to investigate the role of HIFα molecules in inflammatory bowel disease. Methods: Surgical specimens from patients with active ulcerative colitis (UC) and Crohn’s disease (CD) were assessed immunohistochemically for HIF1α and HIF2α reactivity, and the expression of these molecules was compared with the expression of the angiogenic factors thymidine phosphorylase (TP), vascular endothelial growth factor (VEGF), and VEGF–KDR activated vasculature. The vascular density of the lesions was also assessed using anti-CD31 immunostaining. Results: HIF1α was expressed focally (epithelial cells, stromal fibroblasts, and myocytes) in both UC and CD, whereas HIF2α was expressed focally in UC and diffusely in CD. TP expression was uniformly positive in both diseases. VEGF expression was absent in CD, and weakly positive in UC. The VEGF–KDR reactivity of the submucosal vasculature was only slightly increased in UC and CD compared with normal tissue. The inflammatory cells stained with HIF2α and TP in all cases, but the reactivity was generalised in CD and focal in UC. In both diseases, vascular density was significantly higher than that seen in normal tissue. Conclusions: The discordant expression of HIF2α and VEGF in CD suggests an inherent deficiency of the intestine to respond to various stresses by the induction of VEGF. This finding should be investigated further.

Evaluation of a Multisensor Armband in Estimating Energy Expenditure in Obese Individuals

Objective: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals.

Association of −634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery

Background.  There is convincing evidence for a central role of vascular endothelial growth factor (VEGF) in fetal and placental angiogenesis. Our present study was undertaken to examine the possible relationship between two common functional VEGF gene polymorphisms (− 634G/C and 936C/T), linked with altered VEGF gene responsiveness, and spontaneous preterm delivery.

Peripheral Neuropathy is Associated With Increased Serum Levels of Uric Acid in Type 2 Diabetes Mellitus

We assessed serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy (diagnosed by the Neuropathy Disability score [NDS]). We enrolled 64 patients with T2DM with peripheral neuropathy (group A: 31 men, mean age 63.0 ± 2.8 years) and 66 age-, gender-, renal function- and T2DM duration-matched patients without neuropathy (group B: 32 men, mean age 62.4 ± 3.1 years). Serum uric acid was significantly higher in group A (P < .001). There was a significant correlation between SUA and NDS in both groups (group A: rs = .93, P < .001; group B: r s = .95, P < .001). C-reactive protein (CRP) was also significantly higher in group A (P < .001) and correlated significantly with SUA in both groups (group A: rs = .93, P < .001; group B: rs = .87, P < .001). Serum uric acid is increased in patients with T2DM with neuropathy versus those without. Whether SUA is involved in the pathogenesis of T2DM peripheral neuropathy remains to be established.

Vascular endothelial growth factor gene polymorphisms and pregnancy

Vascular endothelial growth factor (VEGF) is a major angiogenic factor and prime regulator of endothelial cell proliferation. During pregnancy, VEGF is essential for the proliferation of trophoblasts, the development of embryonic vasculature and the growth of maternal and fetal blood cells in utero. In cases of pre-eclampsia and in some circumstances of preterm labor-raised umbilical cord serum, VEGF levels might be correlated with the clinical development of the above pathological disorders. Genetic alteration as 936C/T VEGF gene polymorphism has a statistical significant correlation with the severity of pre-eclampsia. The same VEGF gene polymorphism, which has been associated with lower protein production, has an increased risk of spontaneous preterm delivery in a Greek-studied population. Homozygotes were found to carry the greatest risk with a lesser proportionate risk associated with heterozygosity, whereas women with the -1154 allele of the VEGF gene have an increased risk of recurrent pregnancy loss. In this review, we present evidence that demonstrates an implication of VEGF gene polymorphisms in the pathological disorders of pregnancy. However, further genetic studies are needed to confirm these data.

Common Variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 Show Evidence of Association With Adult Obesity in the Greek Population

Twenty‐four single‐nucleotide polymorphisms (SNPs) have been reproducibly associated with obesity. We performed a follow‐up study for obesity in the Greek adult population. A total of 510 obese and 469 lean adults were genotyped for 24 SNPs. We tested the association with obesity status using logistic regression and we evaluated the combined genetic risk of 24 SNPs by calculating the area under the receiver‐operating characteristic (ROC) curves. We nominally replicated the association with obesity (BMI ≥30 kg/m2) of six SNPs in or near the FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 loci (1.28 ≤ odds ratio (OR) ≤ 1.35; 0.004 ≤ P ≤ 0.043). The discrimination ability for obesity was slightly stronger (P = 9.59 × 10−6) when the genetic information of the 24 SNPs was added to nongenetic risk factors (area under the curve (AUC) = 0.722) in comparison with nongenetic factors analyzed alone (AUC = 0.685). Our data suggest that SNPs in or near the FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 loci contribute to obesity risk in the Greek population.

A prospective study on the use of the indicator test Neuropad® for the early diagnosis of peripheral neuropathy in type 2 diabetes.

AIM The aim of this prospective study was to evaluate the contribution of the indicator test for sudomotor function Neuropad® to the early diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus. Included were 109 type 2 diabetic patients (55 men, mean age 56.15 ± 6.14 years), whose initial clinical examination (Neuropathy Disability Score, NDS) was negative for neuropathy. Patients were first examined between January and June 2004 and re-examined 5 years later by the NDS and Neuropad ®. Initially, 70 patients (64.22%) had normal and 39 (35.78%) patients had abnormal Neuropad® (groups A and B, respectively). NDS was significantly higher in group B on both examinations (p < 0.001). On the second examination, 2 patients (2.86%) in group A and 10 patients (25.64%) in group B had developed neuropathy (p = 0.001). Neuropad® had 83.33% sensitivity and 68.04% specificity for neuropathy. There was a modest but significant agreement (kappa = 0.259, p < 0.001) between Neuropad® and NDS for neuropathy. CONCLUSIONS Among type 2 diabetic patients with normal NDS, development of neuropathy is significantly more frequent in those with abnormal Neuropad®. These results suggest a potential utility of Neuropad® for the earlier diagnosis of neuropathy in type 2 diabetes.

Accuracy of the Neuropad Test for the Diagnosis of Distal Symmetric Polyneuropathy in Type 2 Diabetes

OBJECTIVE To estimate the accuracy of Neuropad for the diagnosis and staging of distal symmetric polyneuropathy (DPN) across different stages of neuropathy, using multiple-level likelihood ratios (LRs) to interpret the time necessary to complete the color change of the test. RESEARCH DESIGN AND METHODS We conducted a cross-sectional, cohort-type diagnostic accuracy study in 251 consecutive adult type 2 diabetic patients with no peripheral arterial disease or other potential causes of neuropathy, who were recruited between January 2005 and December 2008 from the diabetes outpatient clinics in Alexandroupolis Hospital, Greece. Patients were tested for DPN by means of the neuropathy disability score (NDS) and Neuropad. Multiple-level LRs for time to complete color change were calculated across different stages of neuropathy. RESULTS The areas under the curve for the diagnosis of any (NDS of ≥3), at least moderate (NDS of ≥6), or severe (NDS of ≥9) DPN were 0.91, 0.96, and 0.97, respectively. The calculation of multiple-level LRs showed that time to complete color change <360 s suggested the absence of neuropathy. Values between 360 and 1,000 s were indicative of mild neuropathy. Finally, values between 1,000 and 1,200 or >1,200 s were strongly suggestive of moderate or severe DPN, respectively. CONCLUSIONS Neuropad could be used as a triage test for the diagnosis and staging of DPN in patients with type 2 diabetes, prompting referral to specialized care setting.

Association between foot temperature and sudomotor dysfunction in type 2 diabetes.

Background and Aims: Increased foot skin temperature has been described as a feature of diabetic neuropathy. The aim of this present study was to investigate the association between foot temperature and sudomotor dysfunction in type 2 diabetes mellitus. Patients and Methods: This study included 51 patients (group A: 25 men, mean age 61.14 ± 6.11 years) without sudomotor dysfunction and 52 patients (group B: 25 men, mean age 59.54 ± 6.18 years) with sudomotor dysfunction. Sudomotor dysfunction was defined as time until complete Neuropad™ color change from blue to pink exceeding 600 s in at least one foot. Time until complete color change of the test was also recorded. Foot skin temperature was measured with a handheld infrared thermometer on the plantar aspect of the foot at the level of the first metatarsal head. Results: On both feet, temperature was significantly higher in group B than in group A (right foot, group A versus group B, 30.62 ± 1.13 °C versus 32.12 ± 1.06 °C, p < .001; left foot, group A versus group B, 30.65 ± 1.06 °C versus 32.19 ± 1.10 °C, p < .001). There was a significant positive correlation between time to complete Neuropad color change and foot skin temperature (right foot, r = 0.742, p < .001; left foot, r = 0.758, p < .001), which was confirmed in both groups. Conclusions: Patients with sudomotor dysfunction have significantly higher foot temperature than those without sudomotor dysfunction. Foot temperature is positively correlated with severity of sudomotor dysfunction, as evaluated by the time to complete Neuropad color change.

Umbilical cord serum vascular endothelial growth factor (VEGF) levels in normal pregnancies and in pregnancies complicated by preterm delivery or pre-eclampsia

Objectives: The aim of this study was to determine whether increased levels of vascular endothelial growth factor (VEGF) are implicated in the pathogenesis of pre‐eclampsia and in preterm delivery. Methods: Umbilical cord serum VEGF levels from women with uncomplicated term pregnancies (control group, n=24), with pregnancies complicated by pre‐eclampsia (n=21), or with preterm delivery (n=29) were compared. Statistical analysis was performed using the Mann–Whitney U‐test, the t‐test, and Smirnoff–Kolmogorov test. Results: The mean VEGF concentration was significantly higher in the women with pre‐eclampsia than in women from the control group (P<0.01). There were also increased but not significantly higher VEGF concentrations in the preterm delivery group compared with the control group (P=0.16). Conclusions: Our study results support previous findings that raised umbilical cord serum VEGF levels might be correlated with the clinical development of pre‐eclampsia and, in some circumstances, of preterm delivery.