Cloning, characterization and subcellular localization of a Trypanosoma cruzi argonaute protein defining a new subfamily distinctive of trypanosomatids.

Over the last years an expanding family of small non-coding RNAs (sRNA) has been identified in eukaryotic genomes which behave as sequence-specific triggers for mRNA degradation, translation repression, heterochromatin formation and genome stability. To achieve their effectors functions, sRNAs associate with members of the Argonaute protein family. Argonaute proteins are segregated into three paralogous groups: the AGO-like subfamily, the PIWI-like subfamily, and the WAGO subfamily (for Worm specific AGO).

Benznidazole blocks NF-kappaB activation but not AP-1 through inhibition of IKK.

Previously, we demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, modulates pro-inflammatory cytokines and NO release in macrophages by inhibiting NF-kappaB. We now proceeded to elucidate the molecular mechanisms by which BZL exerts its inhibitory action on NF-kappaB. We demonstrated that the inhibitory effect of BZL is not extended to other macrophage responses, since it did not inhibit other typical hallmarks of macrophage activation such as phagocytosis, MHC-II molecules expression or production of reactive oxygen species (ROS) by NADPH oxidase.

Thoracic epidural analgesia in lung transplantation.

Achieving optimal pain relief after lung transplantation (LT) is often difficult, because both systemic analgesics and regional techniques have specific advantages and disadvantages. Uncontrolled pain impedes repeated powerful coughs and hinders valid respiratory excursions and graft expansion; these consequences markedly increase the risk of pulmonary complications. Thoracic epidural analgesia (TEA) is a universally accepted method of pain management after unilateral or bilateral thoracotomy, and in clinical experience it has proven to be the best option after LT.

Metal-modified and vertically aligned carbon nanotube sensors array for landfill gas monitoring applications.

Vertically aligned carbon nanotube (CNT) layers were synthesized on Fe-coated low-cost alumina substrates using radio-frequency plasma enhanced chemical vapour deposition (RF-PECVD) technology. A miniaturized CNT-based gas sensor array was developed for monitoring landfill gas (LFG) at a temperature of 150 degrees C. The sensor array was composed of 4 sensing elements with unmodified CNT, and CNT loaded with 5 nm nominally thick sputtered nanoclusters of platinum (Pt), ruthenium (Ru) and silver (Ag).

Follow-up of adolescents with diabetes after transition from paediatric to adult care: results of a 10-year prospective study.

Objective: Our main objective in this study was to identify the type of clinical care received by young type 1 diabetic patients who have made the transition from paediatric to adult care, and to assess the metabolic status of long-term treatment after the transition.

Methods: A standardized questionnaire was used prospectively to follow 99 patients with type 1 diabetes mellitus after their transition to adult care. This survey was done once a year, from 1998 to 2008.

Bevacizumab-related osteneocrosis of the jaw.

We describe a case of jaw bone necrosis after a lung adenocarcinoma bone metastasis, treated the first time in 2004 by means of pneumonectomy and lymph node ablation. One week after a dental extraction, the patient experienced pain in the mandibular region, in conjunction with alveolar bone exposure. Treatment with amoxicillin and clavulanate every 12 hours for 15 days and 0.

Orbital abscess after facial trauma.

This paper reports a rare case of acute severe orbital abscess manifested 2 days after a facial trauma without bone fracture in a 20-year-old Afro-American female. The symptoms worsened within the 24 h prior to hospital admission resulting in visual disturbances such as diplopia and photophobia. The clinical findings at the first consultation included fever, periorbital swelling and redness, ptosis, proptosis and limitation of ocular movements upwards, downwards, to the right and to the left.

Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene.

Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable.

New generic primer system targeting mucosal/genital and cutaneous human papillomaviruses leads to the characterization of HPV 115, a novel Beta-papillomavirus species 3.

We explored the cutaneotropic HPV genetic diversity in 71 subjects from Argentina. New generic primers (CUT) targeting 88 mucosal/cutaneous HPV were designed and compared to FAP primers. Overall, 69 different HPV types/putative types were identified, being 17 of them novel putative types.

Modulation of aberrant NF1 pre-mRNA splicing by kinetin treatment.

Neurofibromatosis type 1 is one of the most common neurocutaneous autosomal dominant disorders. It is caused by mutations in the neurofibromatosis type 1 (NF1) gene and approximately 30-40% of them affect the correct splicing of NF1 pre-mRNA. In this report, we evaluate the effect of five different drugs, previously found to modify splicing in several genetic disorders, on the splicing of mutated NF1 alleles.

Trypanosoma cruzi TBP shows preference for C/G-rich DNA sequences in vitro.

Recent findings associate transcription start in trypanosomatids with chromatin regions containing modified and variant histones. TATA-binding protein (TBP) and other fundamental transcription factors have been also found at these Transcription Start Sites (TSS). Results of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) experiments show that Trypanosoma cruzi TBP (TcTBP) has an in vitro binding preference for G-rich sequences.

Non-invasive ventilation in prone position for refractory hypoxemia after bilateral lung transplantation.

Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary.

Therapeutic efficacy and safety of amitriptyline in patients with cystic fibrosis.

Amitriptyline, a blocker of acid sphingomyelinase and acid ceramidase, significantly reduces Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) mice with concurrent increase of survival. Our aim was to establish whether amitriptyline is safe and effective in the treatment of CF patients. In a randomised, double-blinded, placebo-controlled, cross-over pilot study, 4 adult CF patients received 37.

Noninvasive ventilation in postoperative care of lung transplant recipients.

Noninvasive positive pressure ventilation (NIPPV), which provides consolidated treatment of both acute and chronic respiratory failure, is increasingly being used in the postoperative care of lung transplant patients. Graft- and patient-related respiratory insufficiency requiring mechanical ventilation are common features in the postoperative period; they may persist for hours to days. Prolonged intubation, particularly in these immunocompromised patients, has been considered one of the main predisposing factors for developing nosocomial pneumonia.

Hemodynamic profile of portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) refers to the development of pulmonary arterial hypertension in the setting of portal hypertension with or without chronic hepatic failure. This syndrome is characterized by marked alternations of pulmonary vascular tone and obstruction of pulmonary arterial blood flow. An increased pulmonary blood flow, which is a hallmark of the hyperdynamic circulation of cirrhotic patients, seems to be present in almost all patients who develop PPHTN.

Influence of topical anaesthesia on the corticomotor response to tongue training.

Objectives: The aim of this experimental study was to investigate if perturbation of somatosensory function would change corticomotor excitability of the tongue musculature in relation to a novel tongue training task.

Materials And Methods: Sixteen healthy volunteers participated in two randomized and double-blind sessions separated by two weeks, in which topical anaesthetics or placebo cream were applied to the tongue during a standardized tongue training task. Corticomotor excitability was assessed by changes in motor evoked potentials (MEPs) in the tongue musculature evoked by transcranial magnetic stimulation (TMS) before and after training.

Novel cytostatic activity of the trypanocidal drug Benznidazole.

We have shown that Benznidazole (BZL), a compound with well documented trypanocidal activity, possesses anti-inflammatory properties and inhibits the nuclear factor kappaB (NF-kappaB). Given the relationship between this transcription factor and cell growth, in this study we address the role of NF-kappaB blockade by BZL in the proliferation of different cell lines. Our studies demonstrate that this compound significantly reduced proliferation of RAW 264.

Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1:3,500 individuals. Disease expression is highly variable and complications are diverse. However, currently there is no specific treatment for the disease.

Trypanosoma cruzi bromodomain factor 2 (BDF2) binds to acetylated histones and is accumulated after UV irradiation.

Histone tail post-translational modifications (acetylation, methylation, phosphorylation, ubiquitination and ADP-ribosylation) regulate many cellular processes. Among these modifications, phosphorylation, methylation and acetylation have already been described in trypanosomatid histones. Bromodomains, together with chromodomains and histone-binding SANT domains, were proposed to be responsible for "histone code" reading.

Negative feedback that improves information transmission in yeast signalling.

Haploid Saccharomyces cerevisiae yeast cells use a prototypic cell signalling system to transmit information about the extracellular concentration of mating pheromone secreted by potential mating partners. The ability of cells to respond distinguishably to different pheromone concentrations depends on how much information about pheromone concentration the system can transmit. Here we show that the mitogen-activated protein kinase Fus3 mediates fast-acting negative feedback that adjusts the dose response of the downstream system response to match the dose response of receptor-ligand binding.

The Alpha Project: a model system for systems biology research.

One goal of systems biology is to understand how genome-encoded parts interact to produce quantitative phenotypes. The Alpha Project is a medium-scale, interdisciplinary systems biology effort that aims to achieve this goal by understanding fundamental quantitative behaviours of a prototypic signal transduction pathway, the yeast pheromone response system from Saccharomyces cerevisiae. The Alpha Project distinguishes itself from many other systems biology projects by studying a tightly bounded and well-characterised system that is easily modified by genetic means, and by focusing on deep understanding of a discrete number of important and accessible quantitative behaviours.

Beneficial effects of benznidazole during an infectious-based situation of systemic inflammatory response: cecal ligation and puncture.

We have shown that benznidazole (BZL), a drug used to treat Chagas disease, markedly reduced the production of pro-inflammatory cytokines and NO-derived metabolites in experimentally Trypanosoma cruzi-infected rats. Treatment with BZL exerted beneficial effects in a model of inflammation-based pathology like murine experimental endotoxemia. Based on these findings, we wished to ascertain the effect of BZL in a closer situation to sepsis: the cecal ligation and puncture (CLP) model in C57BL/6 mice.

One- and two-hybrid analysis of the interactions between components of the Trypanosoma cruzi spliced leader RNA gene promoter binding complex.

The spliced leader (SL) RNA gene promoter is the only RNA polymerase II-dependent promoter characterized to date in trypanosomatids. Transcription of this small nuclear RNA is critical for trypanosomatid cell life because it is needed for polycistronic primary transcripts processing into individual translatable mRNAs. In recent years, a set of divergent fundamental transcription factors required for SL RNA gene transcription have been identified in different trypanosomatids.

Duloxetine and pregabalin: safe and effective for the long-term treatment of fibromyalgia?

This Practice Point commentary discusses the first two trials of long-term drug treatment in fibromyalgia. In Russell et al.'s study, 33% of patients receiving 6-month treatment with 60 mg/day duloxetine responded to therapy; the number needed to treat was seven.