Cobalt-56 γ-ray emission lines from the type Ia supernova 2014J.

A type Ia supernova is thought to be a thermonuclear explosion of either a single carbon-oxygen white dwarf or a pair of merging white dwarfs. The explosion fuses a large amount of radioactive (56)Ni (refs 1-3). After the explosion, the decay chain from (56)Ni to (56)Co to (56)Fe generates γ-ray photons, which are reprocessed in the expanding ejecta and give rise to powerful optical emission. Here we report the detection of (56)Co lines at energies of 847 and 1,238 kiloelectronvolts and a γ-ray continuum in the 200-400 kiloelectronvolt band from the type Ia supernova 2014J in the nearby galaxy M82. The line fluxes suggest that about 0.6 ± 0.1 solar masses of radioactive (56)Ni were synthesized during the explosion. The line broadening gives a characteristic mass-weighted ejecta expansion velocity of 10,000 ± 3,000 kilometres per second. The observed γ-ray properties are in broad agreement with the canonical model of an explosion of a white dwarf just massive enough to be unstable to gravitational collapse, but do not exclude merger scenarios that fuse comparable amounts of (56)Ni.

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. MATERIAL AND METHODS: 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the treatment group, ASCs were applied instead of saline solution. The control and treatment groups were subdivided based on the time of euthanasia. A clinical and histological analysis was performed. RESULTS: The presence of osteonecrosis in alveolar bone was observed in a similar distribution in both groups. In the ASC-treated group, new bone formation was greater than in controls. CONCLUSION: In this study, application of ASCs showed greater new bone formation in an osteonecrosis-like murine model. Previous inhibited post-extraction bone remodelling could be reactivated, and these findings appeared to be secondary to implantation of ASCs.

Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country.

Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.

Testing the model of caudo-rostral organization of cognitive control in the human with frontal lesions.

The cascade model of cognitive control, mostly relying on functional neuroimaging studies, stipulates that the lateral frontal cortex (LFC) is organized as a cascade of executive processes involving three levels of cognitive control, implemented in distinct LFC areas from the premotor to the anterior prefrontal regions. The present experiment tested this model in patients with LFC lesions and studied the hierarchy of executive functions along the caudo-rostral axis, i.e. the respective roles of the different LFC areas in the control of behavior. Voxel-based lesion-symptom mapping and region of interest group analyses were conducted in 32 patients with focal LFC lesions who performed cognitive tasks assessing the cascade model. We first showed that three different LFC areas along the caudo-rostral axis subserved three distinct control levels, whose integrity is necessary for adaptive behavior. Second, we found that prefrontal cognitive control has an asymmetric organization: higher control processes involving more anterior prefrontal regions rely on the integrity of lower control processes in more posterior regions, while lower control processes can operate irrespective of the integrity of higher control processes. Altogether, these findings support a caudo-rostral cascade of executive processes from premotor to anterior prefrontal regions.

[Severe decompensation of hepatitis e in a patient with autoimmune hepatitis: a case report]. / Severa descompensación por virus de hepatitis e en una paciente con hepatitis autoinmune: reporte de un caso.

We report the case of a patient who initially made the diagnosis of acute hepatitis E virus with a clinical picture of jaundice with elevated liver enzymes and HEV IgM (+), but chronic evolution (More than 6 months) without being an immunosuppressed patient, forced us to exclude different causes that may produce chronic liver disease. And hypergammaglobulinemia was detected in liver biopsy: interface hepatitis, mixed inflammatory infiltrate with predominance of lymphocytes, and presence of portal-portal fibrous tracts, suggestive of severe active chronic hepatitis may be secondary to autoimmune hepatitis associated with hepatitis virus infection E. With these findings, we decided to start treatment for autoimmune hepatitis with prednisone and azathioprine, leading to a decrease in transaminases and coagulation profile to normal, which helped confirm the diagnosis of autoimmune hepatitis and decompensated manifested by acute virus infection of hepatitis E. Full report the case and a review of the literature.

Anaemia, iron and vitamin deficits in patients with peripheral arterial disease.

INTRODUCTION: Anaemia can compromise muscle and organ function. Related iron and vitamin body stores have seldom been assessed in patients with peripheral arterial disease. REPORT: We retrospectively analysed basal prevalence of anaemia, iron, B(12)-vitamin and folic acid deficits in 420 patients with claudication and 204 patients with critical limb ischaemia (CLI). The prevalence of the evaluated parameters was 9.8%, 6.7%, 6.7% and 2.9% among patients with claudication but 49.5%, 31.9%, 15.7% and 6.4% among CLI patients, respectively (p < 0.05 for all). DISCUSSION: Anaemia, iron and vitamin deficits are uncommon among patients with ischemic claudication but very prevalent among patients with CLI.

Causal role of prefrontal cortex in the threshold for access to consciousness.

What neural mechanisms support our conscious perception of briefly presented stimuli? Some theories of conscious access postulate a key role of top-down amplification loops involving prefrontal cortex (PFC). To test this issue, we measured the visual backward masking threshold in patients with focal prefrontal lesions, using both objective and subjective measures while controlling for putative attention deficits. In all conditions of temporal or spatial attention cueing, the threshold for access to consciousness was systematically shifted in patients, particular after a lesion of the left anterior PFC. The deficit affected subjective reports more than objective performance, and objective performance conditioned on subjective visibility was essentially normal. We conclude that PFC makes a causal contribution to conscious visual perception of masked stimuli, and outline a dual-route signal detection theory of objective and subjective decision making.

Clinical utility of temozolomide in the treatment of malignant paraganglioma: a preliminary report.

We report on the efficacy and safety of short-term administration of temozolomide, an inhibitor of nucleoside incorporation, in a 60-year-old woman with widespread hepatic metastases from a malignant paraganglioma. Temozolomide was orally administered in daily doses of 250 mg on days 1 to 5 and repeated every 28 days for five cycles. Clinical improvement was immediate and associated with weight gain, and further reduction in blood pressure without ortho-static intolerance. In addition, abnormal hepatic function was normalized and catecholamine production was significantly reduced. Except for mild nausea, adverse effects were virtually absent. Bone marrow function, renal function, and serum electrolytes remained normal; hemoglobin remained above 9 g/dl through treatment. The platelet count decreased but not to clinically meaningful levels. These responses allowed for a surgical debulking procedure to be performed safely without complications. The results suggest that temozolomide may be useful in presurgical preparation of patients with pheochromocytoma especially in those with widespread metastatic disease and poor physical condition. However, the present findings need confirmation in a larger study and the role of temozolomide in the long-term treatment of malignant paraganglioma/pheochromocytoma remains to be established.

Production, characterization, and expression of neuropeptide Y by human pheochromocytoma.

Neuropeptide Y (NPY) levels are increased in plasma and tumors of patients with pheochromocytoma. The present study was designed to evaluate plasma and tissue NPY levels simultaneously as well as to study its release and expression in patients with either adrenal or extraadrenal pheochromocytomas. Plasma NPY levels were higher (P < 0.01) in patients with adrenal tumors than in matched normal subjects and patients with extraadrenal tumors. NPY levels were also higher (P < 0.05) in adrenal than in extraadrenal tumors. Bioactive NPY (1-36) was the predominant form in plasma and tumors of patients with adrenal pheochromocytomas. In contrast, patients with extraadrenal pheochromocytomas had an abundance of NPY fragments. NPY mRNA was abundant in 11 of 13 adrenal tumors but in only 1 of 6 extraadrenal tumors. Moreover, NPY was coreleased with NE with manipulation of adrenal but not extraadrenal tumors. These findings indicate that increased NPY gene expression in adrenal pheochromocytomas accounts for the greater biosynthesis and storage of NPY in these tumors and that increased release of NPY results in elevated plasma NPY. Factors regulating NPY gene expression in pheochromocytoma and the role of NPY in the clinical manifestations of the disease remain to be elucidated.

Abnormal membrane sodium transport in Liddle's syndrome.

We have documented the presence of abnormal sodium transport in Liddle's syndrome by measuring sodium concentration, sodium influx, and fractional sodium outflux in vitro in erythrocytes from normal subjects, two patients with Liddle's syndrome, and one patient with primary hyperaldosteronism. Sodium influx and fractional sodium outflux, but not sodium concentration, were significantly increased in patients with Liddle's syndrome. Sodium outflux in a patient with primary hyperaldosteronism did not differ significantly from normal. These alterations of sodium transport in erythrocytes from patients with Liddle's syndrome were not attributable to circulating levels of aldosterone, renin, angiotensin, or serum potassium. Furthermore, changes in aldosterone secretory rate and levels of circulating renin produced by varying dietary sodium intake, did not alter sodium influx or fractional sodium outflux in either patients with Liddle's syndrome or normal subjects. The response of fractional sodium outflux and sodium influx to ouabain, ethacrynic acid, and to changes in the cation composition of the incubation medium suggests that the increased sodium fluxes in Liddle's syndrome do not result solely from a quantitative increase in those components of sodium transport which occur in normal human erythrocytes. Instead, at least a portion of the increased erythrocyte sodium transport in Liddle's syndrome represents a component of sodium transport which does not occur in normal human erythrocytes.

Changes in cholesterol metabolism are associated with PS1 and PS2 gene regulation in SK-N-BE.

Several lines of evidence suggest that the cholesterol content of neuronal membranes influences amyloid precursor protein (APP) processing; however, its role in transcriptional regulation of the cofactors for gamma-secretase, the key enzyme for the production of the Abeta peptide, is poorly understood. This study investigates whether the changes in cellular cholesterol metabolism modulate the expression of genes involved in the gamma-secretase complex function. The abundance of mRNA transcripts for presenilin 1 and 2 (PS1 and PS2), APP, and nicastrin were evaluated in neuroblastoma cells exposed either to serum-depleted medium or to low-density lipoproteins (LDL). Cholesterol esterification was markedly inhibited by mevinolin and U18666A, but was not significantly affected by any other of the tested treatments. gamma-Secretase genes and cofactors were not co-regulated and were not influenced by statin inhibition of cholesterol synthesis. Nicastrin and the APP isoforms showed constitutive expression. In the absence of exogenous lipids, cell PS1 and PS2 expression was induced by LDL and by lysosomal sequestration of cholesterol. However, a different pattern of induction of presenilin gene expression was observed in the latter condition, suggesting that lysosomal cholesterol levels are strong inducers of PS2 transcription. Taken together, these results indicate that lipid metabolism has a complex influence on gamma-secretase transcriptional pathways and, in particular, exogenous cholesterol and compartmentalization in neuroblastoma cells play a relevant role in regulating the transcription of presenilins, while modulation of the cholesterol biosynthesis pathway seems to exert a minor influence on the expression of gamma-secretase genes and cofactors.

Determination of omeprazole, hydroxyomeprazole and omeprazole sulfone using automated solid phase extraction and micellar electrokinetic capillary chromatography.

A sensitive method for the determination of omeprazole and its metabolites has been developed. It involves an automated solid phase extraction (SPE) procedure and capillary electrophoresis with UV detection. Omeprazole, hydroxyomeprazole and omeprazole sulfone could be separated by micellar electrokinetic capillary chromatography using a background electrolyte composed of 20 mM borate buffer and 30 mM sodium dodecyl sulfate, pH 9.5. The isolation of omeprazole and its metabolites from plasma was automatically accomplished with an original SPE procedure using surface-modified styrene-divinylbenzene polymer cartridges. Good recovery data and satisfactory precision values were obtained. Responses were linear for the three analytes, from 0.08 to 2.0 microg/mL of plasma. Intra- and inter-day precision values of about 1.6% R.S.D. (n=10) and 2.5% R.S.D. (n=36), respectively, were obtained. The method is highly robust and no breakdown of the current or capillary blockages were observed during several weeks of operation. The validated method was applied to the determination of omeprazole in pharmaceutical preparations and for the analysis of plasma samples obtained from three volunteers who received oral doses of omeprazole.

Cyclosporine-associated leukoencephalopathy in organ transplant recipients: experience of three clinical cases.

Leukoencephalopathy is a structural alteration of cerebral white matter mainly involving damage to myelin. Several reports have linked cyclosporine (CsA) with this alteration. The clinical features vary from qualitative alterations of consciousness to neurological deficits. Magnetic resonance imaging (MRI) of the brain demonstrates the damage to the white matter, which is essential for the differential diagnosis. We describe three clinical cases of leukoencephalopathy. The first case is a 43-year-old man received a cadaveric kidney transplant using immunosuppression with of mycophenolate mofetil, prednisone, and CsA. Four months later he developed meningism and bilateral sixth nerve palsy. The second case is a 50-year-old man with a cadaveric kidney transplant received immunosuppressive treatment with azathioprine and prednisone. As a result of gouty arthritis of the ankle, azathioprine was replaced with CsA to allow addition of allopurinol. Two weeks later he developed confusion and personality changes. The third case is a 16-year-old man received a orthotopic liver transplant. Postoperatively he suffered generalized tonic-clonic seizures. In all patients the CsA levels were toxic and signs of neurological alterations were present on MRI. All patients recovered rapidly after CsA withdrawal.

Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation.

A new triptorelin 11.25 mg long depot formulation is now available for the treatment of central precocious puberty (CPP). The aim of our study was to evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to suppress gonadotropin and sex steroid secretion and pubertal signs in children with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal development before the age of 8 years in girls or 9 years in boys, advanced bone age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2 years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum levels of LH and FSH decreased significantly from baseline to 3 months of therapy (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and 24 months of treatment. The pituitary-gonadal axis recovered adequately after discontinuation of therapy. These results suggest that 3-month depot triptorelin is a satisfactory alternative for the therapy of children with CPP. The longer interval between injections may increase acceptability and compliance with treatment.