Long-term vitamin E supplementation fails to reduce lipid peroxidation in people at cardiovascular risk: analysis of underlying factors

BACKGROUND: Antioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action. METHODS: We examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged ≥ 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF(2α) (isoprostane F(2α)-III or 15-F(2t)-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry. RESULTS: Urinary excretion of 8-epi-PGF(2α) [pg/mg creatinine, median (range)] was 141 (67–498) in treated and 148 (76–561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that vitamin E had no significant effect on this biomarker. Levels of 8-epi-PGF(2α) were in the normal range for most subjects, except smokers and those with uncontrolled blood pressure or hyperglycemia. CONCLUSIONS: Prolonged vitamin E supplementation did not reduce lipid peroxidation in subjects with major cardiovascular risk factors. The observation that the rate of lipid peroxidation was near normal in a large proportion of subjects may help explain why vitamin E was not effective as an antioxidant in the PPP study and was ineffective for CVD prevention in large scale trials

Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells

VizieR Online Data Catalog: C2O and C3O in low-mass star-forming region

Data reported in Figure 1 correspond to newly detected C2O and lines towards: L1544 (panels A, B, C, D, E and F); L1498 (panels G and H); and Elias 18 (panels I and J). Each panel reports the molecule and its transition. The detection reported in panel G (performed with the Noto-32m telescope) was acquired with a lower resolution than that used for the observations reported in the other panels (IRAM-30m telescope). For clarity we give a larger VLSR scale that allows a better evaluation of the baseline. Table 1 and Table 2 in the paper report information on the spectroscopic parameters and telescope used. Further details are given in Section 2 in the paper. Files are given in FITS and ASCII format for each panel. (3 data files)

Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system

The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from L-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell-axon relationship causing axonal damage and regulating endoneurial cell life and death

Decreased osteocyte viability in multiple myeloma patients: osteolytic bone lesions, apoptosis and their potential role in bone remodeling alterations.

Osteocytes seem to regulate bone remodelling by different manners including apoptosis. A reduction of osteocyte viability (OC-V) was shown in osteoporotic bone. Osteolysis/osteoporosis, induced by multiple myeloma (MM), are characterized by severely imbalanced uncoupled bone remodelling due to increased osteoclastogenesis and suppressed osteoblast differentiation occurring close to MM cell infiltration. The aim of this study is to investigate the eventual involvement of osteocytes in bone remodelling alterations occurring in MM patients. Iliac crest biopsies were taken from 34 patients with MM (52% of which displayed osteolytic bone lesions), 10 with monoclonal gammopathy of uncertain significance (MGUS) and 10 without haematological malignancies/osteoporosis/metabolic bone diseases. Viable osteocytes and degenerated or apoptotic osteocytes/empty lacunae were evaluated on 500 lacunae per histological section. Significant reductions of OC-V in MM patients were found compared to healthy controls, whereas not statistical significance in OC-V was observed between MM and MGUS. Death osteocytes/empty lacunae number was significantly increased in MM vs. controls but not as compared to MGUS. Concerning the skeletal involvement, in MM patients either OC-V percentage was significantly lower in osteolytic vs. non-osteolytic patients or the number of dead osteocytes/empty lacunae was higher in osteolytic vs. non-osteolytic patients. Monolayers were also performed of human preosteocytes incubated with/without conditioned media (CM) taken from human myeloma cell lines (HMCLs) or co-cultured with them, and TEM observations showed dead cells in those monolayers treated with HMCL-CM or co-cultured with HMCLs as compared to non treated cells. In CM of preosteocytes co-cultured with HMCLs significantly increased CD14+-derived osteoclastogenesis occurs, evaluated by TRAP staining and pit-forming assay. Our data demonstrate that MM bone is characterized by reduction of OC-V; the increase of osteocyte death (apoptosis/degeneration) in relation to the presence of bone lesions may represent a triggering event to osteoclast recruitment

Sympathectomy alters bone architecture in adult growing rats

Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone