Delayed presentation of an arteriovenous malformation after cerebellar hemangioblastoma resection—Case report

AbstractIntroductionHaemangioblastoma has been uncommonly reported to occur in coexistence either temporally or spatially with the development of an arteriovenous malformations (AVM). We present a case of a delayed AVM following haemangioblastoma resection.Presentation of case44 year old female initially presented with a several week history of headaches, vertigo and nausea and emesis and was found to have a cystic lesion with a solid enhancing component on Magnetic Resonance Imaging (MRI) in the superior aspect of the vermis. She underwent gross total resection and final pathology was consistent with WHO grade I haemangioblastoma. One year later, patient re-presented with headaches, dizziness and left trochlear nerve palsy with rotary nystagmus. Imaging revealed a left posterior tentorial paramedian cerebellar vascular nidus with venous drainage into the left transverses sinus suspicious for arteriovenous malformation. She underwent gross total resection of the lesion. Final pathology confirmed the diagnosis of an arteriovenous malformation.DiscussionRecent research supports both haemangioblastoma and AVM are of embryologic origin but require later genetic alterations to develop into symptomatic lesions. It is unclear in our case if the AVM was present at the time of the initial haemangioblastoma resection or developed de novo after tumor resection. However, given the short time between tumor resection and presentation of AVM, de novo AVM although possible, appears less likely.ConclusionAVM and haemangioblastoma rarely presents together either temporally or spatially. We present a case of a delayed AVM following haemangioblastoma resection. More research is needed to elucidate the rare intermixture of these lesions

Persistent changes in lipoprotein lipids after a single infusion of ascending doses of MDCO-216 (apoA-IMilano/POPC) in healthy volunteers and stable coronary artery disease patients

Background and aims: Effects of single ascending doses of MDCO-216 on plasma lipid and lipoprotein levels were assessed in human healthy volunteers and in patients with stable coronary artery disease (CAD). Methods: MDCO-216 was infused at a single dose of 5, 10, 20, 30 or 40 mg/kg over 2 h and blood was collected at 2, 4, 8, 24, 48, 168 and 720 h after start of infusion (ASOI). Lipoprotein lipids were assessed by FLPC and by 1H NMR. Results: Plasma concentrations of free cholesterol (FC) displayed a rapid and dose-dependent rise, peaking at 8 h, but remaining above baseline until 48 h ASOI, whereas levels of esterified cholesterol (CE) increased at lower doses but not at higher doses, and even decreased below baseline at the highest dose. Plasma cholesterol esterification rate (CER) decreased with a first nadir between 4 and 8 h and a second nadir at 48 h ASOI. Taken over all subjects receiving MDCO-216, the increase in FC at 8 h correlated inversely with the drop in CER at 4 h but positively with the increase in basal and scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux capacities at 2 h ASOI. Upon FPLC analysis, FC was found to increase first in high density lipoproteins (HDL) and very low density lipoproteins (VLDL) and later (at 48 or 168 h ASOI) in low density lipoproteins (LDL). CE initially decreased in LDL and HDL but after 24 h started to increase in VLDL and LDL whereas HDL-CE was still below baseline at 48 h. Phospholipids (PL) showed the same pattern as FC. Triglycerides (TG) also rose rapidly, most prominently in VLDL, but also in LDL and HDL. Apolipoprotein E (Apo-E) in VLDL increased at 4-8 h but returned to baseline at 24 h ASOI. 1H NMR analysis showed a rapid and dose-dependent increase in HDL particle size, peaking at 2 h and returning to baseline at 24 h, and a small increase in HDL particle concentration. After infusion of the 40 mg/kg dose, LDL and VLDL-particles also increased in number and size. Conclusions: A single administration of MDCO-216 caused rapid changes in lipid levels and lipoprotein composition, some of which persisted for at least 7 days

Exercise Training Amount and Intensity Effects on Metabolic Syndrome (From Studies of a Targeted Risk Reduction Intervention through Defined Exercise)

Although exercise improves individual risk factors of the metabolic syndrome (MS), there is little research on the effect of exercise on MS as a whole. The objective of this study was to determine how much exercise is recommended to reduce the prevalence of MS. Of 334 subjects randomized, 227 finished and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III- defined MS risk factors and were included in this analysis. Subjects were randomly assigned to a six-month control or 1 of 3 eight-month exercise training groups: 1) low-amount/moderate-intensity (equivalent to walking ~19 km/week); 2) low-amount/vigorous-intensity (equivalent to jogging ~19 km/week); 3) high-amount/vigorous-intensity (equivalent to jogging ~32 km/week). The low- amount/moderate-intensity exercise prescription improved MS relative to inactive controls (p<0.05). However, the same amount of exercise at a vigorous intensity was not significantly better than inactive controls, suggesting that lower intensity exercise may be more effective in improving MS. The high-amount/vigorous-intensity group improved MS relative to controls (p<0.0001), the low- amount/vigorous-intensity group (p=0.001), and the moderate intensity group (p=0.07), suggesting an exercise dose effect. In conclusion, a modest amount of moderate intensity exercise, in the absence of dietary changes, significantly improved MS and thus supports the recommendation that adults get 30 minutes of moderate intensity exercise every day. A higher amount of vigorous exercise was shown to have greater and more widespread benefits. Finally, there is an indication that moderate intensity may be better than vigorous intensity exercise for improving MS. Originally published American Journal of Cardiology, Vol. 100, No. 12, Dec 200

Immunodetection of retinoblastoma-related protein and its phosphorylated form in interphase and mitotic alfalfa cells

Plant retinoblastoma-related (RBR) proteins are primarily considered as key regulators of G1/S phase transition, with functional roles in a variety of cellular events during plant growth and organ development. Polyclonal antibody against the C-terminal region of the Arabidopsis RBR1 protein also specifically recognizes the alfalfa 115 kDa MsRBR protein, as shown by the antigen competition assay. The MsRBR protein was detected in all cell cycle phases, with a moderate increase in samples representing G2/M cells. Antibody against the human phospho-pRb peptide (Ser807/811) cross-reacted with the same 115 kDa MsRBR protein and with the in vitro phosphorylated MsRBR protein C-terminal fragment. Phospho-MsRBR protein was low in G1 cells. Its amount increased upon entry into the S phase and remained high during the G2/M phases. Roscovitine treatment abolished the activity of alfalfa MsCDKA1;1 and MsCDKB2;1, and the phospho-MsRBR protein level was significantly decreased in the treated cells. Colchicine block increased the detected levels of both forms of MsRBR protein. Reduced levels of the MsRBR protein in cells at stationary phase or grown in hormone-free medium can be a sign of the division-dependent presence of plant RBR proteins. Immunolocalization of the phospho-MsRBR protein indicated spots of variable number and size in the labelled interphase nuclei and high signal intensity of nuclear granules in prophase. Structures similar to phospho-MsRBR proteins cannot be recognized in later mitotic phases. Based on the presented western blot and immunolocalization data, the possible involvement of RBR proteins in G2/M phase regulation in plant cells is discussed

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

Abstract Background In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile. Methods NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. Results Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). Conclusions The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008–13, this study was not registered in clinicaltrials.gov

El Niño, tropical Atlantic warmth, and Atlantic hurricanes over the past 1500 years

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 880-883, doi:10.1038/nature08219.Atlantic Tropical Cyclone (TC) activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise. Here, we place recent activity in a longer-term context, by comparing two independent estimates of TC activity over the past 1500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate employs a previously published statistical model of Atlantic TC activity driven by proxy-reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic TC activity during Medieval times (around AD 1000) followed by a subsequent lull in activity. The Medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results in the statistical model from a ‘perfect storm’ of La Niña-like climate conditions and relative tropical Atlantic warmth.M.E.M. and Z.Z. acknowledge support from the ATM programme of the National Science Foundation (grant ATM-0542356). J.P.D. acknowledges support from the EAR and OCE programmes of the National Science Foundation (grants EAR-0519118 and OCE-0402746), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences, and the Inter-American Institute for Global Change Research

Propofol Directly Increases Tau Phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology