Capillary hemangioblastoma: histogenesis of stromal cells

Summary The histogenesis of stromal cells in capillary hemangioblastoma has been the subject of debate. The light and electron microscopic studies of hemangioblastomas presented here showed pericytic and leiomyoblastic features in stromal cells. Cells cultured by the monolayer method showed similar features to those of the original tumors. Immunohistochemical studies for glial fibrillary acidic protein and factor VIII/von Willebrand factor indicated that stromal cells were antigenically distinct from astrocytes and endothelial cells. These findings suggest that stromal cells are closely related to pericytes and smooth muscle cells, and support Rhodin's speculation that pericytes serve as a precursor to smooth muscle cells.     

Inadequate dietary magnesium intake increases atherosclerotic plaque development in rabbits

Epidemiological studies have shown dietary magnesium (Mg) intake and serum Mg levels to be inversely correlated with the development of atherosclerosis. We hypothesized that low levels of Mg would promote atherosclerotic plaque development in rabbits. New Zealand white rabbits (4 months old, n = 22) were fed an atherogenic diet containing 0.12% (−Mg), 0.27% (control), or 0.43% (+Mg) Mg for 8 weeks. Blood samples were obtained at baseline, 2, 4, 6, and 8 weeks and were assayed for total cholesterol, high-density lipoprotein (HDL), non-HDL, triglycerides (TG), C-reactive protein, serum Mg, and erythrocyte Mg. Aortas from −Mg had significantly more plaque, with an intima thickness 42% greater than control and 36% greater than +Mg. Serum cholesterol levels rose over time, and at 8 weeks, −Mg had the highest and +Mg the lowest total and non-HDL cholesterol and TG levels, although these results did not reach significance. Over time, serum Mg levels increased, and erythrocyte Mg levels decreased. C-reactive protein significantly increased in all groups at 4 and 6 weeks but returned to baseline levels by 8 weeks. This study supports the hypothesis that inadequate intake of Mg results in an increase in atherosclerotic plaque development in rabbits.     

Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

Effects of self-management training in Type 2 diabetes: a randomized, prospective trial.

AIMS: The efficacy of three education programmes for Type 2 diabetic patients was tested in a randomized trial. A didactic-oriented training programme (treatment A) was compared with a self-management-oriented programme delivered in group sessions (treatment B). The latter programme was compared with a more individualized approach (treatment C). METHODS: One hundred and eighty-one Type 2 diabetic patients (age 55.6 +/- 6.3 years, diabetes duration 6.6 +/- 6.2 years, HbA(1c) 7.8 +/- 1.6%, female 49.7%) took part. Efficacy was assessed 3 months (t1) after baseline (t0) and at a follow-up 15 months (t2) after baseline. RESULTS: The fall in HbA(1c) in treatment B at t1 was sustained at t2 (t0 8.1 +/- 1.8%, t1 7.3 +/- 1.7%, t2 7.4 +/- 1.9%). In treatment A, HbA(1c) was unchanged throughout (t0 7.6 +/- 1.5%, t1 7.5 +/- 1.3%, t2 7.7 +/- 1.7%; treatment A vs. treatment B; P < 0.05). With the more individualized approach of treatment C, there was a fall in HbA(1c) at t1, but this was not sustained at t2 (t0 7.8 +/- 1.6%, t1 7.1 +/- 1.3%, t2 7.6 +/- 1.6%; treatment B vs. treatment C; P = 0.73). There were also significant benefits in treatment B subjects compared with treatment A in further medical (body mass index and fasting blood glucose), psychological (control, irritability and hunger dependency of eating behaviour, and trait anxiety) and behavioural (exercise) variables. There were no significant benefits of the more individualized treatment C compared with group treatment B. No significant differences were found regarding triglyceride levels, high-density lipoprotein, diabetes-related knowledge, negative well-being, urine or blood glucose levels or foot care. CONCLUSION: Self-management training had a significantly higher medium-term efficacy than didactic diabetes education. The group sessions were more effective than a more individualized approach.     

Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies.

AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for-gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2).     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

Investigations into the C‐deuteriation of aryl alkyl ketones using urea as a pro‐base in the presence of a deuterium donor

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd.     

Adenomyosis:common and uncommon manifestations on sonography and magnetic resonance imaging.

OBJECTIVE: The purpose of this presentation is to show the imaging findings of the common and uncommon variants of adenomyosis as seen on sonography and magnetic resonance imaging (MRI). METHODS: A 3-year database search was performed to identify women who had pelvic sonography and pelvic MRI within a 6-month interval. Images of these cases were retrospectively reviewed. RESULTS: Eighty women were identified. Adenomyosis was diagnosed on MRI, which was used as the reference standard, in 45 of these women. The correct diagnosis was made on sonography in 73% of the cases. CONCLUSIONS: Awareness of the spectrum of imaging features of adenomyosis is important to use sonography effectively for diagnosing this entity and to help avoid misdiagnosis.     

Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial.

AIMS: Diabetic ketoacidosis (DKA), a life-threatening acute complication of Type 1 diabetes, may be preventable with frequent monitoring of glycaemia and ketosis along with timely supplemental insulin. This prospective, two-centre study assessed sick day management using blood 3-hydroxybutyrate (3-OHB) monitoring compared with traditional urine ketone testing, aimed at averting emergency assessment and hospitalization. METHODS: One hundred and twenty-three children, adolescents and young adults, aged 3-22 years, and their families received sick day education. Participants were randomized to receive either a blood glucose monitor that also measures blood 3-OHB (blood ketone group, n = 62) or a monitor plus urine ketone strips (urine ketone group, n = 61). All were encouraged to check glucose levels > or = 3 times daily and to check ketones during acute illness or stress, when glucose levels were consistently elevated (> or = 13.9 mmol/l on two consecutive readings), or when symptoms of DKA were present. Frequency of sick days, hyperglycaemia, ketosis, and hospitalization/emergency assessment were ascertained prospectively for 6 months. RESULTS: There were 578 sick days during 21,548 days of follow-up. Participants in the blood ketone group checked ketones significantly more during sick days (276 of 304 episodes, 90.8%) than participants in the urine ketone group (168 of 274 episodes, 61.3%) (P < 0.001). The incidence of hospitalization/emergency assessment was significantly lower in the blood ketone group (38/100 patient-years) compared with the urine ketone group (75/100 patient-years) (P = 0.05). CONCLUSIONS: Blood ketone monitoring during sick days appears acceptable to and preferred by young people with Type 1 diabetes. Routine implementation of blood 3-OHB monitoring for the management of sick days and impending DKA can potentially reduce hospitalization/emergency assessment compared with urine ketone testing and offers potential cost savings.     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.