TIMS measurements of full range of natural Ca isotopes with internally consistent fractionation correction

This study presents static measurements of the Ca isotopic composition of standard reference materials SRM 915 a/b on a Triton Plus™ thermal ionization mass spectrometer with a specially developed Faraday cup array allowing simultaneous measurement of 40Ca and 48Ca. The total amount of Ca in all analyses was kept < 1 µg. With this setup the measurement uncertainties were 0.06 ‰ for 40Ca/44Ca and 0.12 ‰ for 48Ca/40Ca. Measuring all isotopes simultaneously better allows to test the internal consistency of different Ca isotope abundances reported in the literature. The exponential law was observed to correct incompletely instrumental mass fractionation. An improved fractionation correction based on the exponential law is proposed. It changes the 40Ca/44Ca ratio of SRM 915a (corrected relative to 42Ca/44Ca = 0.31221; 48Ca/44Ca = 0.08871) from 47.1635 ± 0.0028 to 47.1649 ± 0.0047. The measurements of SRM 915b were performed with different analytical conditions (runs were prolonged till complete filament load depletion). Even if the 40Ca/44Ca ratio of SRM 915b, when corrected with the simple exponential law, appears different (47.1532 ± 0.0038) from that of SRM 915a, it becomes coincident (47.1613 ± 0.0028) when corrected with a second-order refinement. This supports the use of the improved exponential law to obtain internally consistent Ca isotope ratio for natural samples.

Association of the (CA)n repeat polymorphism of insulin-like growth factor-I and -202 A/C IGF-binding protein-3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

A number of mathematical models for predicting growth and final height outcome have been proposed to enable the clinician to 'individualize' growth-promoting treatment. However, despite optimizing these models, many patients with isolated growth hormone deficiency (IGHD) do not reach their target height. The aim of this study was to analyse the impact of polymorphic genotypes [CA repeat promoter polymorphism of insulin-like growth factor-I (IGF-I) and the -202 A/C promoter polymorphism of IGF-Binding Protein-3 (IGFBP-3)] on variable growth factors as well as final height in severe IGHD following GH treatment. DESIGN, PATIENTS AND CONTROLS: One hundred seventy eight (IGF-I) and 167 (IGFBP-3) subjects with severe growth retardation because of IGHD were studied. In addition, the various genotypes were also studied in a healthy control group of 211 subjects.

Short-term response of the Ca cycle of a montane forest in Ecuador to low experimental CaCl 2 additions

The tropical montane forests of the E Andean cordillera in Ecuador receive episodic Sahara-dust inputs particularly increasing Ca deposition. We added CaCl2 to isolate the effect of Ca deposition by Sahara dust to tropical montane forest from the simultaneously occurring pH effect. We examined components of the Ca cycle at four control plots and four plots with added Ca (2 × 5 kg ha–1 Ca annually as CaCl2) in a random arrangement. Between August 2007 and December 2009 (four applications of Ca), we determined Ca concentrations and fluxes in litter leachate, mineral soil solution (0.15 and 0.30 m depths), throughfall, and fine litterfall and Al concentrations and speciation in soil solutions. After 1 y of Ca addition, we assessed fine-root biomass, leaf area, and tree growth. Only < 3% of the applied Ca leached below the acid organic layer (pH 3.5–4.8). The added CaCl2 did not change electrical conductivity in the root zone after 2 y. In the second year of fertilization, Ca retention in the canopy of the Ca treatment tended to decrease relative to the control. After 2 y, 21% of the applied Ca was recycled to soil with throughfall and litterfall. One year after the first Ca addition, fine-root biomass had decreased significantly. Decreasing fine-root biomass might be attributed to a direct or an indirect beneficial effect of Ca on the soil decomposer community. Because of almost complete association of Al with dissolved organic matter and high free Ca2+ : Al3+ activity ratios in solution of all plots, Al toxicity was unlikely. We conclude that the added Ca was retained in the system and had beneficial effects on some plants.

Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence

OBJECTIVE We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. DESIGN Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. RESULTS Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. CONCLUSIONS Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain.

In vivo evaluation in cynomolgus monkey brain and metabolism of [¹⁸F]fluorodeprenyl: a new MAO-B pet radioligand

In this study, we evaluated the in vivo characteristics of a new monoamine oxidase type B (MAO-B) radioligand, [¹⁸F]fluorodeprenyl, by positron emission tomography (PET) in two cynomolgus monkeys. The brain uptake of [¹⁸F]fluorodeprenyl was more than 7% (600% SUV) of the total injected radioactivity and similar to that of [¹¹C]deprenyl, an established MAO-B radioligand. The highest uptake was observed in the striatum, one of the MAO-B-rich regions, with a peak at approximately 2-3 min after injection, followed by lower uptake in the thalamus and the cortex and lowest uptake in the cerebellum. Brain uptake of [¹⁸F]fluorodeprenyl was largely inhibited by preadministration of the MAO-B inhibitor, L-deprenyl, whereas clorgyline, a MAO Type A blocker, had no significant inhibitory effect, thus demonstrating selectivity for MAO-B. [¹⁸F]Fluorodeprenyl showed relatively slow metabolism with the presence of two radiometabolite peaks with similar retention time as the labeled metabolites of [¹¹C]deprenyl. These results suggest that [¹⁸F]fluorodeprenyl is a potential PET radioligand for visualization of MAO-B activity.

Endovascular treatment of patients with types A and B thoracic aortic dissection using Relay thoracic stent-grafts: results from the RESTORE Patient Registry

To evaluate the safety and performance of Relay stent-grafts in patients with acute or chronic aortic dissections.

Targets of emerging therapies for viral hepatitis B and C

Viral hepatitis B and C, structurally two completely different viruses, commonly infect human hepatocytes and cause similar clinical manifestations. Since their discovery, IFN has been a pillar in the treatment. However, because of the different natures of the viruses, therapeutic approaches diverge and new treatment targets are tailored specifically for each virus. Herein, the authors analyse therapeutic approaches for hepatitis B virus (HBV) and hepatitis C virus (HCV) and focus on emerging concepts that are under clinical evaluation. In particular, promising viral inhibitors for HBV and HCV are reviewed and the current status of research for gene therapy for HCV is described. Immune therapy is a fast-moving field with fascinating results which include therapeutic vaccines and toll-like receptor agonists that could improve tomorrow's treatment approaches.

A pedigree with autosomal dominant thrombocytopenia, red cell macrocytosis, and an occurrence of t(12:21) positive pre-B acute lymphoblastic leukemia

Sampling and analyzing new families with inherited blood disorders are major steps contributing to the identification of gene(s) responsible for normal and pathologic hematopoiesis. Familial occurrences of hematological disorders alone, or as part of a syndromic disease, have been reported, and for some the underlying genetic mutation has been identified. Here we describe a new autosomal dominant inherited phenotype of thrombocytopenia and red cell macrocytosis in a four-generation pedigree. Interestingly, in the youngest generation, a 2-year-old boy presenting with these familial features has developed acute lymphoblastic leukemia characterized by a t(12;21) translocation. Tri-lineage involvement of platelets, red cells and white cells may suggest a genetic defect in an early multiliear progenitor or a stem cell. Functional assays in EBV-transformed cell lines revealed a defect in cell proliferation and tubulin dynamics. Two candidate genes, RUNX1 and FOG1, were sequenced but no pathogenic mutation was found. Identification of the underlying genetic defect(s) in this family may help in understanding the complex process of hematopoiesis.

Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism contribute to the dyslipidaemia of adult growth hormone deficiency

Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may be, in part, explained by the dyslipidaemia associated with this condition. It is possible that abnormalities of very low density lipoprotein apolipoprotein B-100 (VLDL apoB) metabolism contribute to this dyslipidaemia. To test this hypothesis, we measured VLDL apoB kinetics in adult GH deficient patients (4 females, 3 males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m2; total cholesterol (TC) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL cholesterol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age 47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m2; TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2 mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-(13)C] leucine was administered by a primed (1 mg/kg), constant intravenous infusion (1 mg/kg/hr) and VLDL apoB enrichment with 13C leucine was determined using gas-chromatography mass-spectrometry. The GHD patients had a significantly higher hepatic secretion rate of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and reduced catabolism ofVLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs 24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findings suggest that GH is integrally involved in the regulation of VLDL apoB metabolism.

Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Reactive oxygen intermediates (ROI) contribute to neuronal injury in cerebral ischemia and trauma. In this study we explored the role of ROI in bacterial meningitis. Meningitis caused by group B streptococci in infant rats led to two distinct forms of neuronal injury, areas of necrosis in the cortex and neuronal loss in the dentate gyrus of the hippocampus, the latter showing evidence for apoptosis. Staining of brain sections with diaminobenzidine after perfusion with manganese buffer and measurement of lipid peroxidation products in brain homogenates both provided evidence that meningitis led to the generation of ROI. Treatment with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN) (100 mg/kg q8h i.p.) beginning at the time of infection completely abolished ROI detection and the increase in lipidperoxidation. Cerebral cortical perfusion was reduced in animals with meningitis to 37.5+/-21.0% of uninfected controls (P < 0.05), and PBN restored cortical perfusion to 72.0+/-8.1% of controls (P < 0.05 vs meningitis). PBN also completely prevented neuronal injury in the cortex and hippocampus, when started at the time of infection (P < 0.02), and significantly reduced both forms of injury, when started 18 h after infection together with antibiotics (P < 0.004 for cortex and P < 0.001 for hippocampus). These data indicate that the generation of ROI is a major contributor to cerebral ischemia and necrotic and apoptotic neuronal injury in this model of neonatal meningitis.

NLL QCD contribution of the electromagnetic dipole operator to B -> Xs gamma gamma with a massive strange quark

We calculate the O(αs) corrections to the double differential decay width dΓ77/(ds1ds2) for the process B¯→Xsγγ, originating from diagrams involving the electromagnetic dipole operator O7. The kinematical variables s1 and s2 are defined as si=(pb−qi)2/m2b, where pb, q1, q2 are the momenta of the b quark and two photons. We introduce a nonzero mass ms for the strange quark to regulate configurations where the gluon or one of the photons become collinear with the strange quark and retain terms which are logarithmic in ms, while discarding terms which go to zero in the limit ms→0. When combining virtual and bremsstrahlung corrections, the infrared and collinear singularities induced by soft and/or collinear gluons drop out. By our cuts the photons do not become soft, but one of them can become collinear with the strange quark. This implies that in the final result a single logarithm of ms survives. In principle, the configurations with collinear photon emission could be treated using fragmentation functions. In a related work we find that similar results can be obtained when simply interpreting ms appearing in the final result as a constituent mass. We do so in the present paper and vary ms between 400 and 600 MeV in the numerics. This work extends a previous paper by us, where only the leading power terms with respect to the (normalized) hadronic mass s3=(pb−q1−q2)2/m2b were taken into account in the underlying triple differential decay width dΓ77/(ds1ds2ds3).