A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Combined T2 -preparation and two-dimensional pencil-beam inner volume selection.

PURPOSE: To improve coronary magnetic resonance angiography (MRA) by combining a two-dimensional (2D) spatially selective radiofrequency (RF) pulse with a T2 -preparation module ("2D-T2 -Prep"). METHODS: An adiabatic T2 -Prep was modified so that the first and last pulses were of differing spatial selectivity. The first RF pulse was replaced by a 2D pulse, such that a pencil-beam volume is excited. The last RF pulse remains nonselective, thus restoring the T2 -prepared pencil-beam, while tipping the (formerly longitudinal) magnetization outside of the pencil-beam into the transverse plane, where it is then spoiled. Thus, only a cylinder of T2 -prepared tissue remains for imaging. Numerical simulations were followed by phantom validation and in vivo coronary MRA, where the technique was quantitatively evaluated. Reduced field-of-view (rFoV) images were similarly studied. RESULTS: In vivo, full field-of-view 2D-T2 -Prep significantly improved vessel sharpness as compared to conventional T2 -Prep, without adversely affecting signal-to-noise (SNR) or contrast-to-noise ratios (CNR). It also reduced respiratory motion artifacts. In rFoV images, the SNR, CNR, and vessel sharpness decreased, although scan time reduction was 60%. CONCLUSION: When compared with conventional T2 -Prep, the 2D-T2 -Prep improves vessel sharpness and decreases respiratory ghosting while preserving both SNR and CNR. It may also acquire rFoV images for accelerated data acquisition.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.

There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. Irradiation and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8(+) T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and irradiation induced CD8(+) T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local irradiation and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intratumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early-phase clinical trials.

Regenerated cellulose ultrafiltration membranes in the treatment of pulp and paper mill process waters

Ultrafiltration (UF) is widely applied in different separation processes in the pulp and paper industry. The growing need to protect the environment, a lack of pure water and an interest in producing high-value chemicals from compounds present in process waters will probably lead to an increase in the use of UF in the pulp and paper industry. The efficiency and cost-effectiveness of a UF process depends on the applied membrane. The membrane should have a high and stable filtration capacity, a particular selectivity and a long operational lifetime. To meet these requirements a membrane should have a low fouling tendency. In addition, it should withstand the prevailing operational and chemical conditions. This thesis evaluates the performance and applicability of the regenerated cellulose (RC) membranes 00030T and C2 in the treatment of pulp and paper mill process waters based on the requirements above. The results demonstrated that both the tested RC membranes fulfilled well the requirement of high filtration capacity. In addition, in the filtration of a paper mill clear filtrate (CF) the RC membranes were not as greatly affected by variations in the CF quality as a polysulphone membrane. Furthermore, due to their extreme hydrophilicity and weak charge the fouling tendency of the membranes can be expected to be low in pulp and paper mill filtration applications. It is, however, known that fouling cannot be totally avoided even when the membrane is chosen very carefully. This study indicated that carbohydrates influenced negatively on permeability and caused fouling in the filtration of groundwood mill circulation water. Thus, a pre-treatment effectively reducing the amount of carbohydrates might help to maintain a stable capacity. However, the results of the thesis also showed that the removal of some of the possible foulants might just increase the harmful effect of others. Multivariate examination was useful in the understanding of the complicated factors causing the unstable capacity. The thesis also revealed that the 00030T and C2 membranes can be used at high pressure (max. tested pressure 12 bar). The C2 membrane, having a sponge-like substructure, was more pressure resistant, and its performance was more stable at high pressure compared to the UCO30T membrane containing macrovoids in its substructure. Both tested membranes can, according to the results, also be used at temperatures as high as 70°C in acidic, neutral and alkaline conditions. However, the use at extreme conditions might cause faster ageing of the membranes compared to ageing in neutral conditions. The thesis proved that both the tested RC membranes are very suitable for pulp and paper mill applications and that the membranes can be utilised in processes operating in challenging conditions. Thus, they could be used in more demanding applications than supposed earlier.

Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-highperformance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry

The present work describes the development of a fast and robust analytical method for the determination of 53 antibiotic residues, covering various chemical groups and some of their metabolites, in environmental matrices that are considered important sources of antibiotic pollution, namely hospital and urban wastewaters, as well as in river waters. The method is based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UHPLC–QqLIT). For unequivocal identification and confirmation, and in order to fulfill EU guidelines, two selected reaction monitoring (SRM) transitions per compound are monitored (the most intense one is used for quantification and the second one for confirmation). Quantification of target antibiotics is performed by the internal standard approach, using one isotopically labeled compound for each chemical group, in order to correct matrix effects. The main advantages of the method are automation and speed-up of sample preparation, by the reduction of extraction volumes for all matrices, the fast separation of a wide spectrum of antibiotics by using ultra-high-performance liquid chromatography, its sensitivity (limits of detection in the low ng/L range) and selectivity (due to the use of tandem mass spectrometry) The inclusion of β-lactam antibiotics (penicillins and cephalosporins), which are compounds difficult to analyze in multi-residue methods due to their instability in water matrices, and some antibiotics metabolites are other important benefits of the method developed. As part of the validation procedure, the method developed was applied to the analysis of antibiotics residues in hospital, urban influent and effluent wastewaters as well as in river water samples

Distinct contributions of Brodmann areas 1 and 2 to body ownership.

Although body ownership-i.e. the feeling that our bodies belong to us-modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.

Trigeminal Neuralgia Secondary to Intracranial Lesions: A Prospective Series of 17 Consecutive Cases

Object: The purpose of the study was to assess the role of Gamma Knife surgery (GKS) in secondary trigeminal neuralgia (TN) caused by space-occupying lesions. Methods: From July 2010 till January 2015, 17 patients had GKS for secondary TN caused by intracranial lesions. The primary outcome was tumor control. The secondary outcomes were the alleviation of pain and the eventual secondary effects. Covariates were the age, duration of symptoms, duration till alleviation etc. Results: The mean age in this series was 63.3 years (range 39-79). The mean follow-up period was 1.85 years (range 0.5-3). Nine (52.9%) were meningiomas, five (29.4%) trigeminal schwannomas, two (11.8%) brain metastases and one (5.9%) arteriovenous malformation (AVM). Eight were located on the right side and nine on the left side. The mean duration of TN was 13.5 months (range 0.5-160). Follow-up was available for 16 patients (94.1%). Pain alleviation appeared after a mean time of 4.6 months (1-11) in 15 patients (88.2%). Five (29.4%) patients completely stopped medication in a mean time of 7 months (range 1-13) and three (17.6%) decreased it at half of the initial doses. No patient developed new hypoesthesia or other cranial nerve complication. The marginal doses for meningiomas and trigeminal schwannomas were 12 Gy (12-14), for metastasis 20 (20-20) and for AVM 24 Gy. The mean target volume was 1.84 cc (range 0.12-8.10). The mean prescription isodose volume was 2.65 cc (0.19-11.90). The mean maximal diameter was 19.9 (range 9-36). The mean number of isocenters was 14.2 (4-27). The mean duration was 76.9 minutes (range 25-172). The mean conformity, selectivity, Paddick and gradient index were: 0.99 (range 0.955-1), 0.701 (range 0.525-0.885), 0.694 (range 0.525-0.885) and 2.904 (range 2.654-3.371). At last follow-up, tumor decreased in 10 (58.8%) patients, was stable in 6 (35.3%) and increased in one (5.9%), the latest at 6 months. Conclusions: Gamma Knife surgery is safe and effective in treating intracranial lesions presenting with secondary TN. The initial pain freedom response was close to 90%, while having no secondary effect. Pain alleviation is achieved even in the absence of a volume variation of the lesions.

Validació del mètode analític per la determinació d'aminoàcids i carbohidrats d'un producte farmacèutic per HPLC

Per poder desenvolupar un producte farmacèutic és necessari establir un mètode d’anàlisis que permeti determinar i quantificar totes aquelles substàncies que conté, ja sigui referent als principis actius; a les impureses i productes de degradació, conservants, antioxidants,... Grans entitats com la ICH remarquen la importància de validar els mètodes analítics ja que és la via per demostrar que aquell producte compleix les garanties de qualitat prèviament establertes. Així doncs, l’objectiu d’aquest Treball Final de Grau és poder desenvolupar i validar dos mètodes analítics per a la determinació d’aminoàcids i carbohidrats respectivament, d’un producte farmacèutic per cromatografia líquida (HPLC). Per tal de poder concloure que aquell mètode és adequat per la determinació per la qual ha estat desenvolupat, és necessari obtenir resultats que compleixin els criteris d’acceptació corresponents als paràmetres que han de ser avaluats en una validació analítica. Aquests paràmetres són: la precisió, la selectivitat, l’exactitud i la linealitat i el rang. Els resultats d’aquest projecte han demostrat que els dos mètodes desenvolupats són adequats per a la determinació de tres dels principis actius (aminoàcid 1, aminoàcid 2 i carbohidrat 1) que conté el producte farmacèutic d’ús veterinari analitzat; i poden ser validats ja que compleixen els criteris d’acceptació dels paràmetres avaluats que proposa la ICH. El mètode per la determinació de carbohidrats no és vàlid per el carbohidrat 2, ja que durant el desenvolupament es va detectar que una bona part d’aquest passava a carbohidrat 1 (desplaçament de l’equilibri ceto-enòlic que hi ha entre el carbohidrat 1 i el carbohidrat 2 a pHs alts). És per aquest motiu, que es pot concloure que aquest mètode no és vàlid i es recomana seguir investigant per a poder desenvolupar un mètode analític adient.

Systematic evaluation of matrix effects in hydrophilic interaction chromatography versus reversed phase liquid chromatography coupled to mass spectrometry.

Reversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent a viable alternative to RPLC for the analysis of polar and/or ionizable compounds, as it often provides higher MS sensitivity and alternative selectivity. Nevertheless, this technique can be also prone to matrix effects (ME). ME are one of the major issues in quantitative LC-MS bioanalysis. To ensure acceptable method performance (i.e., trueness and precision), a careful evaluation and minimization of ME is required. In the present study, the incidence of ME in HILIC-MS/MS and RPLC-MS/MS was compared for plasma and urine samples using two representative sets of 38 pharmaceutical compounds and 40 doping agents, respectively. The optimal generic chromatographic conditions in terms of selectivity with respect to interfering compounds were established in both chromatographic modes by testing three different stationary phases in each mode with different mobile phase pH. A second step involved the assessment of ME in RPLC and HILIC under the best generic conditions, using the post-extraction addition method. Biological samples were prepared using two different sample pre-treatments, i.e., a non-selective sample clean-up procedure (protein precipitation and simple dilution for plasma and urine samples, respectively) and a selective sample preparation, i.e., solid phase extraction for both matrices. The non-selective pretreatments led to significantly less ME in RPLC vs. HILIC conditions regardless of the matrix. On the contrary, HILIC appeared as a valuable alternative to RPLC for plasma and urine samples treated by a selective sample preparation. Indeed, in the case of selective sample preparation, the compounds influenced by ME were different in HILIC and RPLC, and lower and similar ME occurrence was generally observed in RPLC vs. HILIC for urine and plasma samples, respectively. The complementary of both chromatographic modes was also demonstrated, as ME was observed only scarcely for urine and plasma samples when selecting the most appropriate chromatographic mode.

Aetiologies of pulseless electrical activity in out-of-hospital cardiac arrests:A retrospective study and analysis of specific causes

Background: Pulseless electrical activity (PEA) cardiac arrest is defined as a cardiac arrest (CA) presenting with a residual organized electrical activity on the electrocardiogram. In the last decades, the incidence of PEA has regularly increased, compared to other types of CA like ventricular fibrillation or pulseless ventricular tachycardia. PEA is frequently induced by reversible conditions. The "4 (or 5) H" & "4 (or 5) T" are proposed as a mnemonic to asses for Hypoxia, Hypovolemia, Hypo- /Hyperkalaemia, Hypothermia, Thrombosis (cardiac or pulmonary), cardiac Tamponade, Toxins, and Tension pneumothorax. Other pathologies (intracranial haemorrhage, severe sepsis, myocardial contraction dysfunction) have been identified as potential causes for PEA, but their respective probability and frequencies are unclear and they are not yet included into the resuscitation guidelines. The aim of this study was to analyse the aetiologies of PEA out-of-hospital CA, in order to evaluate the relative frequencies of each cause and therefore to improve the management of patients suffering a PEA cardiac arrest. Method: This retrospective study was based on data routinely and prospectively collected for each PEMS intervention. All adult patients treated from January 1st 2002 to December 2012 31st by the PEMS for out-of-hospital cardiac arrest, with PEA as the first recorded rhythm, and admitted to the emergency department (ED) of the Lausanne University Hospital were included. The aetiologies of PEA cardiac arrest were classified into subgroups, based on the classical H&T's classification, supplemented by four other subgroups analysis: trauma, intra-cranial haemorrhage (ICH), non-ischemic cardiomyopathy (NIC) and undetermined cause. Results: 1866 OHCA were treated by the PEMS. PEA was the first recorded rhythm in 240 adult patients (13.8 %). After exclusion of 96 patients, 144 patients with a PEA cardiac arrest admitted to the ED were included in the analysis. The mean age was 63.8 ± 20.0 years, 58.3% were men and the survival rate at 48 hours was 29%. 32 different causes of OHCA PEA were established for 119 patients. For 25 patients (17.4 %), we were unable to attribute a specific cause for the PEA cardiac arrest. Hypoxia (23.6 %), acute coronary syndrome (12.5%) and trauma (12.5 %) were the three most frequent causes. Pulmonary embolism, Hypovolemia, Intoxication and Hyperkaliemia occurs in less than 10% of the cases (7.6 %, 5.6 %, 3.5%, respectively 2.1 %). Non ischemic cardiomyopathy and intra-cranial haemorrhage occur in 8.3 % and 6.9 %, respectively. Conclusions: According to our results, intra-cranial haemorrhage and non-ischemic cardiomyopathy represent noticeable causes of PEA in OHCA, with a prevalence equalling or exceeding the frequency of classical 4 H's and 4 T's aetiologies. These two pathologies are potentially accessible to simple diagnostic procedures (native CT-scan or echocardiography) and should be included into the 4 H's and 4 T's mnemonic.

Quantitative performance of a quadrupole-orbitrap-MS in targeted LC-MS determinations of small molecules.

High-resolution mass spectrometry (HRMS) has been associated with qualitative and research analysis and QQQ-MS with quantitative and routine analysis. This view is now challenged and for this reason, we have evaluated the quantitative LC-MS performance of a new high-resolution mass spectrometer (HRMS), a Q-orbitrap-MS, and compared the results obtained with a recent triple-quadrupole MS (QQQ-MS). High-resolution full-scan (HR-FS) and MS/MS acquisitions have been tested with real plasma extracts or pure standards. Limits of detection, dynamic range, mass accuracy and false positive or false negative detections have been determined or investigated with protease inhibitors, tyrosine kinase inhibitors, steroids and metanephrines. Our quantitative results show that today's available HRMS are reliable and sensitive quantitative instruments and comparable to QQQ-MS quantitative performance. Taking into account their versatility, user-friendliness and robustness, we believe that HRMS should be seen more and more as key instruments in quantitative LC-MS analyses. In this scenario, most targeted LC-HRMS analyses should be performed by HR-FS recording virtually "all" ions. In addition to absolute quantifications, HR-FS will allow the relative quantifications of hundreds of metabolites in plasma revealing individual's metabolome and exposome. This phenotyping of known metabolites should promote HRMS in clinical environment. A few other LC-HRMS analyses should be performed in single-ion-monitoring or MS/MS mode when increased sensitivity and/or detection selectivity will be necessary.

Eletrodos quimicamente modificados aplicados à eletroanálise: uma breve abordagem

Chemically modified electrodes (CMEs) have been subject of considerable attention since its inception about 23 years ago. CMEs result of a deliberate immobilization of a modifier agent onto the electrode surface obtained through chemical reactions, chemisorption, composite formation or polymer coating. This immobilization seeks transfer the physicochemical properties of the modifier to the electrode surface and thus to dictate and control the behavior of the electrode/solution interface. In recent years the interest in CMEs has increased particularly to enhance the sensitivity and/or the selectivity of electroanalytical techniques. In general higher sensitivity and/or selectivity may be achieved by exploiting one or more of the following phenomena: electrocatalysis, preconcentration and interferents exclusion. This paper deals with the application of CMEs in electroanalysis, including a brief presentation of the more general procedures that have been employed for the modification of electrode surfaces.

Reações de Etanol com CO/H2 na Presença do Sistema Catalítico Ru(acac)3/I-

The hydrocarbonylation reaction of ethanol with a CO/H2 mixture assisted by Ru(acac)3/iodide was investigated. Bronsted and Lewis acids and iodides salt were used as homogeneous promoters. The etherification reaction was the main reaction under typical acidic conditions of the catalytic system. When a hydrocarbon solvent (toluene) was added to the initial reaction, the alcohol conversion and the carbonylation products were increased. The catalytic activity of the Bronsted acids (conv. EtOH = 71-92%) was higher than that of the Lewis acids promoters (conv. EtOH = 65-85%). The salt present the lower catalytic activity among the promoters used. The long time reaction carried out with ethanol showed an increase of the product selectivity of the homologation and carbonylation reactions while the etherification reaction selectivity decreased. The recycled ether led to 60-65% ethanol conversion to C5 and C6 products. The main catalytic species are H+[Ru(CO)3I3]-, [HRu3(CO)11]- and [HRu(CO)4]-. The first one is active in the carbonylation and homologation reactions of alcohols while the two others take part only in the homologation reaction.