Molecular dynamics simulations of an α-synuclein NAC domain fragment with a ff14IDPSFF IDP-specific force field suggest β-sheet intermediate states of fibrillation.

For the discovery of treatments against synucleinopathies, it is necessary to unravel and fully understand the mechanism of fibrillation of proteins involved. Among them, α-synuclein (αS) plays a key role in the development of these diseases through its aggregation into oligomers found in Lewy bodies. However, its structural disorder as an intrinsically disordered protein (IDP) makes its characterization by experimental techniques arduously difficult.

Unravelling Constant pH Molecular Dynamics in Oligopeptides with Explicit Solvation Model.

An accurate description of the protonation state of amino acids is essential to correctly simulate the conformational space and the mechanisms of action of proteins or other biochemical systems. The pH and the electrochemical environments are decisive factors to define the effective pKa of amino acids and, therefore, the protonation state. However, they are poorly considered in Molecular Dynamics (MD) simulations.

Fragment dissolved molecular dynamics: a systematic and efficient method to locate binding sites.

Diverse computational methods to support fragment-based drug discovery (FBDD) are available in the literature. Despite their demonstrated efficacy in supporting FBDD campaigns, they exhibit some drawbacks such as protein denaturation or ligand aggregation that have not yet been clearly overcome in the framework of biomolecular simulations. In the present work, we discuss a systematic semi-automatic novel computational procedure, designed to surpass these difficulties.

On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides.

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades.

Percutaneous Transsternal Cryoablation of Ectopic Parathyroid Adenoma in the Anterior Mediastinum.

Ectopic parathyroid adenomas are common in the context of hyperparathyroidism and represent a unique challenge in terms of localization and treatment. Often they are related to higher serum calcium levels than those associated with parathyroid adenomas in typical locations. Additionally, ectopic adenomas often lead to higher morbidity due to failed parathyroid exploration and multiple attempts at surgical removal.

Regulation of hepcidin expression at high altitude.

Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis through the suppression of the iron regulatory hormone hepcidin. Hypoxia also suppresses hepcidin through a mechanism that is unknown. We measured iron indices and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high altitude (4340 m above sea level), with and without prior intravenous iron loading.

Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial.

Acute mountain sickness (AMS) is a common and disabling condition that occurs in healthy individuals ascending to high altitude. Based on the ability of iron to influence cellular oxygen sensing pathways, we hypothesized that iron supplementation would protect against AMS. To examine this hypothesis, 24 healthy sea-level residents were randomized to receive either intravenous iron(III)-hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro de Pasco, Peru (4340 m).

Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials.

Context: Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude. Recent work has established that the effect of hypoxia on pulmonary arterial pressure may depend on iron status, possibly acting through the transcription factor hypoxia-inducible factor, but the pathophysiological and clinical importance of this interaction is unknown.

Objective: To determine whether increasing or decreasing iron availability modifies altitude-induced hypoxic pulmonary hypertension.

Pulmonary pressure and cardiac function in chronic mountain sickness patients.

Background: Chronic mountain sickness (CMS) is characterized by a loss of adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension (PH), which may lead to cardiac failure, develop in patients. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced PH.

Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment.

Rationale: Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit.

Autonomic adaptations in andean trained participants to a 4220-m altitude marathon.

Purpose: Both training and chronic hypoxia act on the autonomic nervous system. Because trained Andean high-altitude natives could perform a high-altitude marathon (4220 m above sea level) in 02:27:23 h, we hypothesized that living in chronic hypoxia does not limit the training-induced benefits on the autonomic modulation of the heart.

Methods: Trained (N=13) and sedentary (N=11) Andean high-altitude natives performed an active orthostatic test.

[Helical CT of abdominal aorta].

The purpose was to illustrate that single or multirow spiral CT angiography has become the main modality for the examination of the abdominal aorta. Our multidisciplinary group investigates weekly 15 abdominal aortas, with a single slice spiral CT since 1995, and a 4 row detector spiral CT since 1999. CT scans protocols and parameters optimization for the 2 CT systems are described.

[Idiopathic epiphoras in adults treated with lacrymal-nasal stents].

Fluoroscopic nonsurgical placement of an expandable polyurethane stent is less invasive than surgery for the treatment of epiphora due to obstruction of the nasolacrimal duct. It needs to be performed with the collaboration of an ophthalmologist, using a high resolution digital subtraction imaging unit.

[Cost efficiency study of lacrimal canal obstruction treatment].

Objective: To compare three methods used to clear the lacrimal canal.

Patients And Methods: A total of 32 files (20 for the dacryocysto-rhinostomy by endoscopic way, 5 for the dacryocysto-rhinostomy by external way and 7 cases of percutaneous stenting) were reviewed. For each, costs of performed interventions were reviewed.

[CT dacryography without selective lacrimal duct catheterization: review of 39 patients].

Objectives: Dacryographies and CT dacryographies are usually performed after catheterization of a lacrimal canaliculus. We evaluated the quality of opacification on CT scan after simple instillation of contrast medium, without any catheterization.

Patients And Methods: 39 patients (78 nasolacrimal ducts) were examined for lacrimal pathways obstruction by CT scan after instillation of diluted contrast medium.

Analysis of agonist-evoked nitric oxide release from human endothelial cells: role of superoxide anion.

1. Dichlorofluorescein oxidation and electrochemical monitoring of in situ nitric oxide (NO) release from cultured human endothelial cells reveals that agonists such as thrombin and histamine simultaneously stimulate transient superoxide production. 2.

Quinacrine increases endothelial nitric oxide release: role of superoxide anion.

The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM.

Antioxidant properties of trans-epsilon-viniferin as compared to stilbene derivatives in aqueous and nonaqueous media.

trans-Epsilon-viniferin, the dimer of resveratrol, extracted from Vitis vinifera, has been evaluated for its antioxidant capacity. Its properties have been compared to those of resveratrol and synthetic stilbenic derivatives (4-hydroxystilbene, 4,4'-dihydroxystilbene, 3,5-dihydroxystilbene, and trimethylresveratrol), in regard to their liposolubility using two media with different polarity. The bleaching of beta-carotene by lipoperoxyl (LOO.

[Clinical and biological investigation of NO].

Furchgott et al. demonstrated in 1980 that relaxation of arterial smooth muscle cells in response to acetylcholine is dependent on the integrity of endothelium. They named the factor responsible of this intercellular relationship EDRF (Endothelium Derived Relaxing Factor), which was identified 7 years latter as nitric oxide (NO), a free radical gas.

[Value of abdominal-pelvic computed tomography in adult rheumatoid purpura].

Purpose: Henoch-Schonlein purpura is a rare eventuality in adulthood. Abdominal involvement can worsen the short-term prognosis and justify medical treatment to avoid surgery.

Methods: Abdominopelvic computed tomography (CT) was performed in six adult patients (four men and two women; age range, 19-74 years) with Henoch-Schonlein purpura before any treatment.

[Transition metals and nitric oxide production in human endothelial cells].

The bioavailability of endothelial nitric oxide (NO) is regulated by transition metals but their mechanisms of action on NO synthesis and degradation are not clearly understood. Using differential pulse amperometry and NO microelectrodes, local NO concentration was measured at the surface of cultured human umbilical vein endothelial cells (HUVECs) stimulated by histamine or thrombin in the presence of transition metal chelators. The agonist-activated NO release required both extracellular Ca2+ and transition metals.

[Comparative assessment of helical CT-angiography, 2D TOF MR-angiography and 3D gadolinium enhanced MRA in aorto-iliac occlusive disease].

Purpose: To compare helical CT-angiography (CTA) and two techniques of MR angiography (MRA) to conventional angiography in aorto-iliac occlusive disease.

Materials And Methods: The abdominal aorta and iliac arteries in 22 patients (4 for preoperative assessment of abdominal aortic aneurysm and 18 for peripheral vascular disease) were imaged using four techniques: digital subtraction angiography ("gold standard"), 2D TOF MR angiography, 3D Gd-enhanced MR angiography and helical CT angiography. Source (CTA and 2D TOF MRA) and MIPed images (after subtraction measures before and after gadolinium injection for 3D Gd-MRA) were reviewed.

[Radio-anatomic study of the angle of origin of dysplastic renal arteries].

Purpose: To compare the angulation at the origin of dysplastic renal arteries compared to atherosclerotic renal arteries, in order to improve the technique for percutaneous transluminal angioplasty of FMD.

Materials And Methods: Retrospective analysis of 40 aortograms in patients who underwent renal angioplasty for dysplastic stenosis, with comparison with 45 control aortograms (with or without atherosclerotic lesions of the renal arteries). The angle of implantation of the renal arteries was measured relative to the aortic axis in the frontal plane, taking into account only the angulation of its proximal segment.

[Chronic hematic cyst of the orbit (orbital subperiosteal hematoma)].

A case of chronic hematic cyst of the orbit which caused unilateral globe displacement with painful diplopia is described in a 72-year-old man. CT scans showed an extraconal soft tissue mass located between the orbital roof and the superior rectus muscle with a bone lysis. Characteristic appearance on MRI (benign signs, subperiosteal localization of the hematoma) has been confirmed by removal surgery.