Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

ObjectivesWe investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).Design and methodsTwo groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m²) and obese subjects (BMI ≥ 30 kg/m²) (20 each).ResultsPlasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p < 0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA_IR). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p < 0.001).ConclusionVisfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA_IR which may reflect its effects on hepatic insulin sensitivity.     

Is Magnetic Resonance Imaging the 'Reference Standard' for Cardiac Functional Assessment? Factors Influencing Measurement of Left Ventricular Mass and Volumes

Purpose MRI is considered reference standard for the assessment of left ventricular (LV) volume and mass measurements. There are few accepted guidelines for uniform assessment of cardiac function with MRI. We sought to investigate different confounding factors influencing LV measurement results. Material and Methods In 60 diabetic type-II patients (group A) we compared intra-/inter-reader variability of MRI for cardiac function measured twice at a 3 month interval by one MRI trained reader and one untrained. In 20 patients (group B) two different techniques were compared for determining the epicardial and endocardial LV-borders. Results Bland Altman analysis showed excellent intra-observer measurement agreement for the trained reader 1 for EDM (mean=–2.3 (–23.6–19)), EDV (2.9(–9.2–15.0)), ESV (3.3(–5.8–12.4)) and EF (1.2(–3.3–5.7)). Untrained reader 2 measurement agreement was considerably less appropriate for EDM (mean=–8.2 (–25.8–9.5)), EDV (7.8(–5.1–20.7)), ESV (5.3(–8.0–18.6)). Only for EF (0.8 (–6.5–8.1)) results were comparable to reader 1. Inter-observer measurement in the beginning was poor for EDM (–13.5(–55.6–28.6)) and EDV (7.3(–61.9–76.6)), whereas agreement for ESV (2.1(–29.9–34.2)) and EF (–0.9(–11.6–9.9)) was good. After 3 months, measurement agreement for EDM (–5.3 (–46.4–35.8)) was considerably improved, for EDV (0.4(–67.0–66.2)) was excellent, whereas agreement for ESV (3.1(–34.4–28.1)) and EF (–1.7(–13.0–9.6)) was similar. Using different techniques for determining the epicardial and endocardial borders, only end-diastolic volume was unchanged whereas all other parameters were significantly different using the two methods (p ≤ 0.03). Conclusion Intra- and inter-reader variability, analyst experience as well as different techniques for determining the boundaries of the left ventricle significantly affect MRI parameters for cardiac function. These results suggest a need for developing commonly accepted standards for cardiac MRI evaluation.     

Stereotactic radiosurgery versus active surveillance for incidental,convexity meningiomas: a matched cohort analysis from the IMPASSE study

Journal of Neuro-Oncology - The optimal treatment strategy of asymptomatic, convexity meningiomas, remains unclear. The purpose of this study was to define the safety and efficacy of stereotactic...     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

Relationship of increased circulating adrenomedullin with cardiac dysfunction, inflammation, oxidative stress and volume overload in hemodialysis patients

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis. The aim of our study was to investigate whether circulating AM might be related to cardiac function, volume overload, oxidative stress and inflammation in hemodialysis patients. Plasma adrenomedullin, C-reactive protein (CRP), oxidized LDL (ox-LDL), lipoprotein (a), systolic and diastolic cardiac functions were assessed before hemodialysis in 80 patients as well as in 40 healthy control subjects. Plasma adrenomedullin levels were significantly higher in the hemodialysis group compared to the control group. Plasma adrenomedullin levels were negatively correlated with systolic and diastolic blood pressure, S/D ratio, deceleration time, left ventricular ejection fraction, ox-LDL and lipoprotein (a). However, it was positively correlated with CRP, delta body weight, mitral E/A wave, and inferior vena cava diameter. Higher plasma adrenomedullin levels may provide a possible index of cardiac dysfunction, systemic inflammation, and volume overload conditions in haemodialysis patients with concomitant cardiovascular disease. In addition, the negative correlation between ox-LDL, lipoprotein (a) and adrenomedullin may suggest that endogenous AM is an important protective factor in anti-atherosclerosis and might be useful as a new target for prevention and therapy for the disease.     

Oral phosphodiesterase-5 inhibitors: effect of heme oxygenase inhibition on cGMP signalling in rat cavernous tissue

This work postulated that heme oxygenase (HO) is partly responsible for controlling phosphodiesterase-5 inhibitor actions by modulating cyclic guanosine monophosphate (cGMP) cavernous tissue levels. Five hundred and four male Sprague-Dawley rats, divided into five groups, were investigated. Group 1 (n=72) included controls, group 2 (n=72) received sildenafil citrate (Viagra) orally, group 3 (n=72) received vardenafil hydrochloride (Levitra), group 4 (n=72) received tadalafil (Cialis). Group 5 (n=216), subdivided into three subgroups (A, B and C, 72 each), received the same dose of each drug with the HO inhibitor, Zn protoporphyrin. Eight rats from each group/subgroup were killed at 0.5, 1, 2, 3, 4, 6, 18, 24 and 36 h when cGMP levels in the cavernous tissues were estimated. Cavernous tissue cGMP levels increased significantly in sildenafil, vardenafil and tadalafil-treated rats compared to the controls with significant decreases after HO inhibition. It is concluded that the effects of these PDE-5 inhibitors in rat cavernous tissue are partly mediated through HO activity via the cGMP signalling pathway.     

Raised serum level of APRIL in patients with systemic lupus erythematosus: Correlations with disease activity indices

The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p = 0.003 and p ≤ 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r = 0.486 and p = 0.001), BILAG musculoskeletal score (r = 0.848 and p ≤ 0.001) and BILAG cardiorespiratory score (r = 0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE.     

p53 mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian patients

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and 8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 (AGG-->AGT, Arg-->Ser) and codon 248 specific for vinyl chloride contamination (CGG-->TGG, Arg-->Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-genotype-4 sequence.