The role of the osteoprotegerin/RANKL/RANK system in diabetic vascular disease

Over the last years our knowledge on the mechanisms involved in the pathogenesis of cardiovascular disease has been enriched by the discovery of new molecules emerging as novel risk factors. Osteoprotegerin (OPG) is a soluble glycoprotein, member of the tumor necrosis factor (TNF)-related superfamily, involved in bone resorption. It was first described as a key regulator of bone homeostasis and vascular calcification in mice. Clinical studies have suggested that serum OPG is associated with vascular calcification in humans. The role of OPG in the development of macroangiopathy in diabetes is not yet clear. It is possible that the increased OPG levels in diabetes reflect a compensatory response to arterial injury and that it is not involved in the pathogenesis of atherosclerosis. Whether harmful or not, determination of serum OPG levels has been suggested as a prognostic biomarker of cardiovascular disease. In addition, increased OPG levels have been reported in diabetic patients with microvascular complications. The potential of OPG administration for therapeutic reasons is challenging for future investigators. This review summarizes the current knowledge on the association between OPG and macrovascular as well microvascular complications of diabetes.     

Informed consent: how much and what do patients understand?

Objective

We sought to evaluate the degree of patients' understanding of several aspects of the informed consent process for surgery and clinical research.

Methods

We conducted a systematic search of PubMed (1961-2006) to identify relevant articles.

Results

We retrieved 23 and 30 eligible for inclusion articles regarding informed consent for surgery and clinical research, respectively. Regarding surgery, adequate overall understanding of the information provided and of the risks associated with surgery was shown in 6 of 21 (29%) and 5 of 14 (36%) studies providing relevant data, respectively. Regarding clinical research, adequate understanding of the aim of the study, the process of randomization, voluntarism, withdrawal, and the risks and the benefits of treatment was shown in 14 of 26 (54%), 4 of 8 (50%), 7 of 15 (47%), 7 of 16 (44%), 8 of 16 (50%), and 4 of 7 (57%) of studies providing relevant data, respectively. Satisfaction by the amount of the given information was shown in 7 of 12 (58%) studies involving surgery and 12 of 15 (80%) studies involving clinical research.

Conclusions

Further attention should be drawn on enhancing patients' understanding regarding several components of the informed consent process for surgery and clinical research.     

Evolution of OGTT in patients with beta-thalassaemia major in relation to chelation therapy

Glucose metabolism disturbances are frequently reported among patients with beta-thalassaemia major on conventional treatment consisted of regular blood transfusions and adequate chelation treatment. Aim of this study was to evaluate the evolution of oral glucose tolerance test (OGTT) in thalassaemic patients in relation to their chelation treatment. Data from two OGTTs performed with an interval of 2 years were studied retrospectively. Patients considered eligible for this study were those who maintained unchanged chelation treatment and did not receive any anti-diabetic agent during the last 2 years. Thirty-one patients (16 M and 15 F) were enrolled with a mean age of 23.73+/-4.23 years at the end of the study. Patients were divided into three groups concerning chelation treatment. First group was receiving deferoxamine (DFO) by an 8-hourly subcutaneous infusion five-six times a week, second group was chelated with deferiprone (DFP) at a daily dose of 75 mg/kg orally and the third group was receiving combined therapy with DFO (3 days/week) and DFP (daily). At the time of the first OGTT, 26 patients (84%) were found to have normal OGTT; three of them showed an impaired glucose tolerance during second test (one was chelated with DFP and two were receiving combined therapy). None of the five patients with impaired glucose metabolism during the first test became diabetic. On contrary, one patient receiving combined therapy managed to normalize his second OGTT. In contrast with the overall trend of a deteriorating glucose tolerance in the whole patient series, the group receiving combined therapy managed to increased beta-cell function index and decreased insulin resistance index, although not statistically significant when compared to other groups. Further studies are needed to support these preliminary results.     

Pertussis seroprevalence in different age groups in Greece

In order to target the appropriate age population for booster vaccination, we examined the antibody titres against pertussis toxin (PT) in different age groups in immunized and non-immunized individuals. In the immunized population, the highest anti-PT levels were observed in the 0- to 2-y age group and the lowest in the teenager and young adult groups. In contrast, in the control group, anti-PT levels were minimal in infants and young children, increasing in adolescence and early adulthood, and waning after 30 y of age. Antibody levels >30 U/ml were observed with higher frequency in children <2 y of age, in individuals with complete vaccination history and in non-immunized individuals. These findings may have important implications in optimizing vaccination policies.     

Non-arteritic anterior ischaemic optic neuropathy: evaluation of the brain and optic pathway by conventional MRI and magnetisation transfer imaging

The purpose of the study was to examine the brain and the visual pathway of patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using conventional MRI (cMRI) and volumetric magnetisation transfer imaging (MTI). Thirty NAION patients, aged 67.5 ± 8.14 years, and 28 age- and gender-matched controls were studied. MTI was used to measure the magnetisation transfer ratio (MTR) of the chiasm and for MTR histograms of the brain. The presence of areas of white matter hyperintensity (WMH) was evaluated on fluid-attenuated inversion recovery (FLAIR) images. Area of the optic nerves (ONs) and volume of the chiasm were assessed, as were coronal short-tau inversion recovery (STIR) and MTI images, respectively. More areas of WMH were observed in patients (total 419; mean 14.4; SD 19) than in controls (total 127; mean 4.7; SD 5.7), P < 0.001. Area (in square millimetres) of the affected ONs, volume(in cubic millimetres) and MTR (in percent) of the chiasm (10.7 ± 4.6), (75.8 ± 20.2), (56.4 ± 6.5), respectively, were lower in patients than in controls (13.6 ± 4.3), (158.2 ± 75.3) (62.1 ± 6.2), respectively, P < 0.05. Mean MTR of brain histograms was lower in patients (53.0 ± 8.0) than in controls (58.0 ± 5.6), P < 0.05. NAION is characterised by decreased ON and chiasmatic size. The low MTR of the chiasm and brain associated with increased areas of WMH may be suggestive of demyelination and axonal damage due to generalised cerebral vascular disease.     

Norepinephrine in small-for-size liver grafts: an experimental study in pigs

BACKGROUND: Norepinephrine plasma levels may play a role in small-for-size grafts dysfunction at the early posttransplant period. MATERIALS AND METHODS: The 18 pigs used as recipients were assigned to group 1 (n = 6), group 2 (n = 6), and group 3 (n = 6) and given grafts with graft-to-recipient volume ratios of 1:1, 2:3, and 1:3, respectively. Blood serum norepinephrine was measured by high-performance liquid chromatography with electrochemical detection at the following time points: pre-anhepatic period (baseline); anhepatic period; and 30, 60, 180, and 360 min after reperfusion. Graft arterial and portal vein flows were obtained 30, 60, 180, and 360 min after reperfusion by the aid of an ultrasonic flowmeter. Aspartate transferase (AST) and international normalized ratio (INR) were measured before the procedure (baseline), and at 180 and 360 min after reperfusion. RESULTS: Anhepatic phase was characterized by a significant increase (6- to 8-fold) of norepinephrine in all groups (P < 0.05). In groups 1 and 2 plasma norepinephrine returned to normal values 30 min after reperfusion. In group 3, plasma norepinephrine remained significantly increased at every time point of the study compared to groups 1 and 2 (P < 0.001). Hepatic artery and portal vein flows in group 3 were significantly (P < 0.05) reduced and increased, respectively, compared to groups 1 and 2 at all times measured. Liver function tests (AST and INR) 360 min after reperfusion were significantly higher in group 3 compared to groups 1 and 2. CONCLUSIONS: Norepinephrine levels are increased in very small-for-size grafts and this increase may be associated with early graft dysfunction.     

Comparative immunohistochemical analysis of aurora-A and aurora-B expression in human glioblastomas. Associations with proliferative activity and clinicopathological features

In the present study, we carried out a comparative immunohistochemical analysis of aurora-A and aurora-B expression in 40 patients with primary glioblastomas, and attempted to identify any associations with Ki-67 index and the patients’ clinical features. The impact of various treatment modalities and proliferative activity on patient outcome was also assessed.Immunohistochemistry was carried out using formalin-fixed and paraffin-embedded tissue sections.Aurora-A expression was higher in tumors with high Ki-67 expression (p=0.01) and was positively, though marginally, related to aurora-B expression (p=0.085). Aurora-B expression was not linked to Ki-67 expression (p=0.182). Lower aurora-A immunohistochemical expression, chemotherapy administration, and tumor localization in one lobe of the brain implied a greater probability of patient survival in univariate analysis (p=0.044, p=0.008, p=0.041, respectively). Ki-67 and aurora-B immunoreactivities were not associated with patient survival (p=0.918 and p=0.539, respectively).To our knowledge, for the first time, the association between aurora-A and aurora-B expression, the correlation of aurora-A with Ki-67 index, and the prognostic impact of aurora-A expression were assessed in glioblastomas. Although we addressed a prognostic connotation of aurora-A, we presume that aurora-A and aurora-B play a complicated role within glioblastomas. Further examinations of larger series are required, so that definite conclusions can be drawn.     

Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major

Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients’ iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients’ iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.