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Claudina Rodríguez-Bonfante,Aned Amaro,María García,Ligia Elena Mejías Wohlert,Pamela Guillen,Rafael Antonio García,Naysan Alvarez,Marialejandra Díaz,Elsys Cárdenas,Silvia Castillo,Rafael Bonfante-Garrido,Rafael Bonfante-Cabarcas A seroepidemiological survey and vector captures were performed in four rural communities in Andrés Eloy Blanco, Lara State, Venezuela. Systematic random sampling was based on family clusters, with samples drawn from 869 individuals to determine anti-Trypanosoma cruzi and anti-Leishmania sp. antibo... ( view more )dies by indirect immunofluorescence. Positive individuals were defined as > or = 1:32 for anti-T. cruzi antibody and non-reactive to Leishmania sp. antigen, revealing an antibody frequency of 6.9% (n = 60), of whom 46.66% were females and 53.33% males and 60% were over 39 years of age. Some 5 (8.33%) seropositive individuals were under 10 years of age and 10 (16.66%) under 20 years. Rhodnius prolixus and Panstrongylus geniculatus were the triatomines captured, with infestation rates of 1.9% and 10.54%, colonization index of 0% and 18.18% in infested houses, and a T. cruzi infection index of 20% and 5.07%, respectively. The results suggest active Chagas disease transmission in Andrés Eloy Blanco in the last two decades and that P. geniculatus is replacing R. prolixus as the Chagas disease vector. ( view less ) Begoña M Escribano,Francisco M Castejón,Rafael Santisteban,Estrella I Agüera,Pura Tovar,Rafael Vivo,María Dolores Rubio Gender differences have not been shown in relation to the immune system in athletic horses. The aim of the present paper was to elucidate gender differences in the non-specific immune response of the polymorphonuclear neutrophil (PMN), plasma glucose and in hormones before and after an exercise in ... ( view more )the lactate threshold (LT). A group of 12 Anglo-Arabian horses (6 females and 6 males, 4-7 years old) was observed. A submaximal exercise test was carried out at the LT. The results showed that males had a higher PMN percentage, plasma glucose values, Adherence index (AI) and random migration than females. Also, females showed significant negative correlations between cortisol and catecholamines with PMN and glucose with phagocytosis, and positive ones between AI and catecholamines. In males, negative correlations were established between random migration and chemotaxis with cortisol, and positive ones between cortisol and phagocytosis. ( view less ) Mariano García-Borbolla,Omar Araji,Carlos Velazquez,Jose Miguel Barquero,Juan Manuel Contreras,Francisco García,Rafael Hidalgo,Rafael García-Borbolla,Manuel Almendro,Carlos A InfantesSpontaneous coronary artery dissection (SCAD) is a rare cause of acute ischemic coronary events. It is more prevalent in young women, particularly in the peripartum period. In men it is an extremely rare cause. We described the clinical course of a patient, man, presenting pain chest and ventricula... ( view more )r malignant arrhythmias. Four days after admission the patient underwent coronary angiography, showing a large SCAD. After this, he had undergone coronary artery bypass surgery. He presented an angiography and clinical resolution and he was still asymptomatic at a 6-month clinical follow up. Pathophysiologic aspects and treatment options of spontaneous coronary artery dissection are discussed. ( view less ) Angel Asensio,Rafael Cantón,Josep Vaqué,Francisco Calbo-Torrecillas,Rafael Herruzo,José Luis Arribas,M Carmen Sáenz,and Grupo de Trabajo EPINE  INTRODUCTION: This study determines the prevalence of infections by carbapenem-resistant Acinetobacter baumannii (CRAB) in Spain, and identifies trends over time, geographical variations, and factors associated with resistance. METHODS: Yearly prevalence surveys (EPINE, Estudio de Prevalencia de la... ( view more )s Infecciones Nosocomiales en España) during 1999 to 2005 were analyzed, including data on the site of infection, culture, and antimicrobial susceptibility, and characteristics of the patients and hospitals. RESULTS: On average, 246 hospitals/year participated in the survey. A total of 1168 A. baumannii isolates were identified, yielding an infection prevalence rate of 3/1,000 hospitalized patients. Fourteen percent of isolates were related to community-onset infections. The most frequent sites of infection were the respiratory tract (42.2%), surgical wound (15.1%), urinary tract (12.9%), and skin (11.7%). Rate of carbapenem resistance was 34.5% (95% CI, 31.8-37.3), and was even higher among ICU patients (43.8%; 95% CI, 38.9%-48.7%). There were considerable differences between Spanish regions, with the highest rates of resistance in central regions. Higher resistance rates were observed in respiratory tract infections (43%) and catheter-related bacteremia (47.6%) than among other sites of infection (P =.003). Main factors associated with CRAB identified by multivariate analysis were surgical or tracheostomy procedures, use of invasive devices such as urinary, nasogastric, or central venous catheters, and mechanical ventilation, as well as male gender and pressure sores. CONCLUSIONS: The prevalence of CRAB in Spain is very high. Differences in resistance rates have been observed according to geographic region and area of hospitalization. Several invasive procedures, as well as male gender and pressure sores, are associated with higher rates of carbapenem resistance. ( view less ) Antonio Egidio Nardi,Isabella Nascimento,Rafael C Freire,André B Veras,Valfrido L de-Melo-Neto,Alexandre M Valença,Fabiana L Lopes,Gastão L Soares-Filho,Michelle N Levitan,Marcele R de Carvalho,Rafael T da Costa,Anna Lucia King,Marco A Mezzasalma,Leila O Grivet,Arabella Rassi,Marcio Versiani BACKGROUND: Mood disorders are considered related to anxiety disorders and their association may determine clinical course and prognosis. We aimed to describe with retrospective methodology the demographic, clinical, and treatment features in a group of panic disorder comorbid with bipolar I disord... ( view more )er (PD-BI) patients who were been treated for at least 3 year-period and compare them with bipolar I (BI) patients who were treated during the same period. METHOD: We compared the demographic and clinical data of 26 PD-BI, 28 BI, and 25 panic disorder (PD) outpatients without history of comorbidity with mood disorder were diagnosed and treated for at least 3 years in the Federal University of Rio de Janeiro. RESULTS: PD group have a higher educational level, are more married, and are more economically active. In the PD-BI and BI patients the disorders started earlier. They also turn out to have an equivalent pattern in the presence of drug abuse episodes, moderate or severe depressive episodes, psychotic episodes, suicide attempts, maniac episodes, mixed episodes, use of fewer days of antidepressants and benzodiazepines, and use of more days of antipsychotics and mood stabilizers. The PD-BI and the BI groups had a higher frequency of depressive episodes and psychotic episodes. LIMITATIONS: It is a retrospective data description based on a naturalistic treatment. The sample has a small size and the some data could be different in a large sample. CONCLUSION: PD-BI patients have demographic, clinical and therapeutic features similar to BI and the data support its validation as a special severe bipolar I disorder subgroup. ( view less ) Federico Pulido,José R Arribas,Rafael Delgado,Esther Cabrero,Juan González-García,María J Pérez-Elias,Alberto Arranz,Joaquín Portilla,Juan Pasquau,José A Iribarren,Rafael Rubio,Michael Norton,OK04 Study Group  BACKGROUND: Prior attempts to reduce the number of drugs needed to maintain viral suppression in patients with suppressed HIV replication while receiving three antiretroviral drugs have been unsuccessful. METHODS: In 205 patients with suppressed HIV replication on lopinavir-ritonavir and two nucleo... ( view more )sides, this randomized, open-label, non-inferiority clinical trial compared the strategies of continuation of triple therapy versus lopinavir-ritonavir monotherapy followed by reinduction with two nucleosides if virological rebound occurred without genotypic resistance to lopinavir-ritonavir. The primary endpoint was proportion of patients without therapeutic failure, defined as confirmed HIV RNA higher than 500 copies/mL (with exclusion of patients receiving monotherapy who resuppressed to < 50 copies/mL after resuming baseline nucleosides), or loss to follow-up, or change of randomized therapy other than reinduction. RESULTS: At week 48, the percentage of patients without therapeutic failure was 94% in the monotherapy group versus 90% in the triple therapy group (difference,-4%; upper limit of 95% confidence interval for difference, 3.4%). The percentage of patients with HIV RNA 50 copies/mL at 48 weeks by intention-to-treat, missing data or reinductions considered as failures, were 85% in the monotherapy group versus 90% in the triple therapy group (P = 0.31; 95% upper limit of 95% confidence interval for difference, 14%). CONCLUSION: In this trial, 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was non-inferior to continuation of two nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, episodes of low level viremia were more common in patients receiving monotherapy. ( view less ) Lilian Calderón-Garcidueñas,Anna C Solt,Carlos Henríquez-Roldán,Ricardo Torres-Jardón,Bryan Nuse,Lou Herritt,Rafael Villarreal-Calderón,Norma Osnaya,Ida Stone,Raquel García,Diane M Brooks,Angelica González-Maciel,Rafael Reynoso-Robles,Ricardo Delgado-Chávez,William Reed Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in targ... ( view more )et brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment. ( view less ) Rafael Ponce The therapeutic uses of immunostimulatory agents are generally in the treatments of infections or cancer. The traditional example of vaccination is one form of immunostimulation used in the prevention of pathogenic infections or cancer (e.g., human papillomavirus vaccine). Recombinant cytokines are... ( view more ) increasingly used to stimulate immune system function. For example, interferon-alpha (IFNalpha) and interleukin (IL)-2 have been used to treat chronic hepatitis C virus infection and metastatic melanoma, respectively. In contrast, monoclonal antibodies are used to target malignant cells for elimination via antibody-dependent cytotoxicity mechanisms or apoptosis, including the anti-CD20 monoclonal antibody rituximab and the anti-CD56 monoclonal antibody alemtuzumab used in the treatment of B-cell malignancies, and the anti-erb2 receptor antibody trastuzumab used in the treatment of breast cancer. Finally, immunostimulation may develop via modulation of pathways involved in immune system regulation. For example, the anti-CD28 monoclonal antibody TGN1412 was developed as an agonist of regulatory T-cells for treatment of T-cell-mediated chronic inflammatory diseases or leukemias. A panel was convened to discuss potential toxicities associated with immunostimulation. At the Immunotoxicology IV meeting in 2006, a panel, moderated by Dr. Robert House (Dynport Vaccine Co., Frederick, MD), included Drs. Gary Burleson (Burleson Research Technologies, Inc., Raleigh, NC), Kenneth Hastings (US FDA, Center for Drug Evaluation and Research [CDER], Rockville, MD), Barbara Mounho (Amgen, Thousand Oaks, CA), Rafael Ponce (ZymoGenetics, Inc., Seattle, WA), Mark Wing (Huntington Life Sciences, Cambridgeshire, United Kingdom), Lauren Black (Navigators Consulting, Sparks, NV) and Anne Pilaro (US FDA, CDER, Rockville, MD). This paper reviews the major identified toxicities associated with immunostimulation, including the acute phase response, cell and tissue abnormalities/injury, cytokine release/cytokine storm, tumor lysis syndrome, vascular leak, and autoimmunity that were discussed by this panel. ( view less ) Julio Valle Muñoz,Tomás Artaza Varasa,Rafael López Pardo,Rufo Rodríguez Merlo,María José Pérez Grueso,Roberto Martín Escobedo,Mariano Alcántara Torres,Rafael Cuena Boy,José María Carrobles Jiménez OBJECTIVE: Noninvasive diagnosis of atrophic gastritis would help to identify individuals at increased risk of gastric carcinoma. In the present study, we evaluated the utility of a serological panel combining pepsinogen I and II, gastrin-17, and anti-Helicobacter pylori antibodies (Gastropanel) as... ( view more ) a screening method for atrophic gastritis. PATIENTS AND METHODS: The serological panel was evaluated in 56 patients divided in two groups: group 1 consisted of 47 patients with uninvestigated dyspepsia and group 2 was composed of nine consecutive patients with gastric carcinoma. In all patients, we performed endoscopy with biopsies of the gastric antrum and body. Levels of pepsinogen I and II, gastrin-17, and anti-H. pylori antibodies were determined through a specific EIA test (Biohit plc, Helsinki, Finland) in fasting serum samples. RESULTS: Atrophic gastritis was significantly more frequent in patients with gastric carcinoma than in those with dyspepsia (56 vs 6%; p = 0.0015). Agreement between the Gastropanel and gastric histology was good (kappa = 0.68). The sensitivity and specificity of the Gastropanel in the diagnosis of atrophic gastritis was 87.5% and 100%, respectively. However, the Gastropanel would not have detected four of the nine cases of gastric carcinoma, since these tumors arose in stomachs with nonatrophic mucosa. CONCLUSIONS: Gastropanel is a useful noninvasive method for the diagnosis of atrophic gastritis. However, its utility as a screening method is limited by cases of gastric carcinoma that arise in stomachs without atrophic mucosa. ( view less ) Ernesto J Fernández Tagarro,Raquel de Gracia Núñez,Rafael J Sánchez Villanueva,Carmen Riñón Aguilar,Rafael Selgas GutiérrezGranulomatous interstitial nephritides are uncommon entities in routine clinical practice. These entities are usually associated with infectious diseases such as tuberculosis, or immune diseases, such as sarcoidosis, systemic lupus erythematosus or cryoglobulinemia. However, these diseases are most... ( view more ) frequently associated with drug intake, especially antibiotics, proton pump inhibitors and nonsteroidal anti inflammatory drugs. An association with prokinetic agents has not previously been reported. We report the case of a 64-year-old woman who developed acute renal failure with this histological pattern after taking the motility promoter cinitapride without her physician's knowledge. ( view less ) Enyr S Arcieri,Ademir Rocha,Camila N Mendonça,Eduardo G V Andreo,Ioná G A Finotti,Rafael L Furlanetto,Rafael S Arcieri,Flávio J Rocha,Luiz V RizzoThe authors report an unusual case of fungal keratitis caused by Histoplasma capsulatum in a male immunocompetent patient. PCR confirmed the presence of the fungus DNA in the material studied. To our knowledge this is the first reported case in humans described all over the world. Patricia Robledo,Jose M Trigo,Fany Panayi,Rafael de la Torre,Rafael Maldonado RATIONALE: Cannabis is the most widely consumed drug associated with 3,4-methylenedioxymethamphetamine (MDMA) use. OBJECTIVES: This study examines whether low doses of MDMA and delta-9-tetrahydrocannabinol (THC) produce synergistic rewarding/reinforcing effects in mice using the conditioned place p... ( view more )reference (CPP) and operant self-administration paradigms. Changes in dopamine (DA) outflow were monitored in the nucleus accumbens (NAC) after single or combined administration of these compounds. RESULTS: MDMA induced a significant CPP at the dose of 10 mg/kg but not at the dose of 3 mg/kg. THC (0.3 mg/kg) by itself was also ineffective in this paradigm. The combined administration of the low dose of MDMA (3 mg/kg) and THC (0.3 mg/kg) produced CPP, whereas the combination of MDMA (10 mg/kg) and THC (0.3 mg/kg) significantly decreased CPP. Animals treated with THC self-administered a sub-threshold dose of MDMA (0.06 mg/kg per infusion), while animals receiving vehicle did not. However, THC did not modify the self-administration of an effective dose of MDMA (0.125 mg/kg per infusion). In microdialysis studies, a low dose of THC significantly increased DA outflow in the NAC, while a low dose of MDMA did not. When MDMA was administered before THC, DA levels decreased with respect to THC. However, when THC was administered before MDMA, DA levels were not significantly modified with respect to THC. CONCLUSIONS: These results demonstrate that a low dose of THC modifies in different ways (increases and decreases) the sensitivity of animals to the behavioural effects of MDMA and that THC and MDMA converge at a common mechanism modulating DA outflow in the NAC of mice. ( view less ) Rafael B Erlich,Suzana A Kahn,Flávia R S Lima,Angelita G Muras,Rodrigo A P Martins,Rafael Linden,Luciana B Chiarini,Vilma R Martins,Vivaldo Moura Neto Gliomas are tumors derived from glia or their precursors within the central nervous system. Clinically, gliomas are divided into four grades and the glioblastoma multiforme (GBM), also referred as grade IV astrocytoma, is the most aggressive and the most common glioma in humans. The prognosis for p... ( view more )atients with GBM remains dismal, with a median survival of 9-12 months. Despite their striking heterogeneity, common alterations in specific cellular signal transduction pathways occur within most GBMs. Previous work from our group identified the co-chaperone stress-inducible protein 1 (STI1) as a cell surface ligand for cellular prion (PrP(C)), which leads to the activation of several signal transduction pathways, some of which modulate cell survival. In the present work, we used thymidine incorporation assays to investigate the effect of STI1 upon proliferation of the human glioblastoma-derived cell line A172. Here we report that STI1 is secreted by and induces proliferation in tumor cells, an effect that is modulated by the Erk and PI3K pathways, and that, in contrast to glioma cells, STI1 does not induce proliferation of normal glia. In addition, our data suggest the involvement of PrP(C) in STI1-induced proliferation of A172 cells. These results provide initial evidence of a new functional role for STI1 on the physiology of human gliomas, and may lead to the identification of new therapeutic targets in these tumors. ( view less ) César Garriga,María Jesús Pérez-Elías,Rafael Delgado,Lidia Ruiz,Rafael Nájera,Tomàs Pumarola,María del Mar Alonso-Socas,Silvia García-Bujalance,Luis Menéndez-Arias,Spanish Group for the Study of Antiretroviral Drug Resistance  Human immunodeficiency virus type 1 (HIV-1) antiviral drug resistance is a major consequence of therapy failure and compromises future therapeutic options. Nelfinavir and lopinavir/ritonavir-based therapies have been widely used in the treatment of HIV-infected patients, in combination with reverse... ( view more ) transcriptase inhibitors. The aim of this observational study was the identification and characterization of mutations or combinations of mutations associated with resistance to nelfinavir and lopinavir/ritonavir in treated patients. Nucleotide sequences of 1,515 subtype B HIV-1 isolates from 1,313 persons with different treatment histories (including naïve and treated patients) were collected in 31 Spanish hospitals over the years 2002-2005. Chi-square contingency tests were performed to detect mutations associated with failure to protease inhibitor-based therapies, and correlated mutations were identified using statistical methods. Virological failure to nelfinavir was associated with two different mutational pathways. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor-experienced patients. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir-based treatments. Despite the relatively high genetic barrier of some protease inhibitors, a relatively small cluster of mutations, previously selected under drug pressure, can seriously compromise the efficiency of nelfinavir- and lopinavir/ritonavir-based therapies. ( view less ) Pilar Garrido,José Luis González-Larriba,Amelia Insa,Mariano Provencio,Antonio Torres,Dolores Isla,José Miguel Sanchez,Felipe Cardenal,Manuel Domine,Jose Ramon Barcelo,Vicente Tarrazona,Andres Varela,Rafael Aguilo,Julio Astudillo,Ignacio Muguruza,Angel Artal,Florentino Hernando-Trancho,Bartomeu Massuti,Maria Sanchez-Ronco,Rafael Rosell PURPOSE: To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non-small-cell lung cancer patients. PATIENTS AND METHODS: Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles... ( view more ) of cisplatin/gemcitabine/docetaxel, followed by surgery. RESULTS: From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage IIIA and stage IIIB patients. Median survival time was 48.5 months for 62 completely resected patients, 12.9 months for 13 incompletely resected patients, and 16.8 months for 15 nonresected patients (P = .005). Three- and 5-year survival rates were 60.1% and 41.4% for completely resected patients, 23.1% and 11.5% for incompletely resected patients, and 31.1% and 0% for nonresected patients, respectively. In the multivariate analysis, complete resection (hazard ratio [HR] = 0.35; P < .0001), clinical response (HR = 0.32; P < .0001), and age younger than 60 years (HR = 0.64; P = .027) were the most powerful prognostic factors. CONCLUSION: Induction chemotherapy followed by surgery is effective in stage IIIA and in selected stage IIIB patients attaining complete resection. ( view less ) Julio C Rivera,Lilián Yépez-Mulia,Alicia Hernández-Campos,Rafael Moreno-Esparza,Rafael Castillo,Gabriel Navarrete-Vázquez,Inés Fuentes-Noriega,Helgi Jung-Cook Benzimidazole 2-carbamates, such as albendazole (ABZ) and mebendazole (MBZ), used for the treatment of helmintic infections, have low aqueous solubility and poor bioavailability, both of which lead to high interindividual variability when used for human systemic helmintiosis; therefore, it is neces... ( view more )sary to search for new anthelmintics with better biopharmaceutical properties. In the present study the solubility, pKa, logP and apparent permeability in the Caco-2 cells system of four novel anthelmintic (1H-benzimidazol-5(6)-yl)carboxamide derivatives (compounds 1-4) with a 2-methylthyo group were evaluated. Also the pharmacokinetic parameters of compound 1 which in previous studies showed activity similar to ABZ against T. spirallis, was evaluated in BALB/c mice, as a representative molecule of the series. The novel anthelmintics, showed better solubility than ABZ in aqueous acid pH and in organic solvents. The logP, P(app) and Caco-2 data indicate that the 4 derivatives are highly permeable drugs, but it is possible that an efflux system could be involved in the transport of these compounds. Plasma levels of compound 1 and its sulfoxide (compound 5) were high after the first 5 min. This fact strongly suggests that compound 1 is rapidly metabolized in the small intestine. On the other hand, the sulfone metabolite (compound 6) levels were lower than those of compound 5. The half life and mean residence time (MRT) of compound 1 and its main metabolites indicate that their elimination is very rapid. More studies in mammalian species are necessary in order to understand the pharmacokinetic behavior of these novel compounds. ( view less ) Yona Ardiles,Rafael de la Puente,Rafael Toledo,Ceylan Isgor,Kathleen Guthrie Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the... ( view more ) role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-d-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by 3 weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by 8 weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets. ( view less ) Laia Canela,Rafael Luján,Carme Lluís,Javier Burgueño,Josefa Mallol,Enric I Canela,Rafael Franco,Francisco Ciruela Heptaspanning membrane also known as G protein-coupled receptors (GPCR) do interact with a variety of intracellular proteins whose function is regulate receptor traffic and/or signaling. Using a yeast two-hybrid screen, NECAB2, a neuronal calcium binding protein, was identified as a binding partner... ( view more ) for the adenosine A(2A) receptor (A(2A)R) interacting with its C-terminal domain. Co-localization, co-immunoprecipitation and pull-down experiments showed a close and specific interaction between A(2A)R and NECAB2 in both transfected HEK-293 cells and also in rat striatum. Immunoelectron microscopy detection of NECAB2 and A(2A)R in the rat striatopallidal structures indicated that both proteins are co-distributed in the same glutamatergic nerve terminals. The interaction of NECAB2 with A(2A)R modulated the cell surface expression, the ligand-dependent internalization and the receptor-mediated activation of the MAPK pathway. Overall, these results show that A(2A)R interacts with NECAB2 in striatal neurones co-expressing the two proteins and that the interaction is relevant for A(2A)R function. ( view less ) Lara Ferrandiz,David Moreno-Ramirez,Adoracion Nieto-Garcia,Rafael Carrasco,Pedro Moreno-Alvarez,Rafael Galdeano,Esther Bidegain,Juan J Rios-Martin,Francisco M Camacho BACKGROUND: To date, no previous experiences of teledermatology (TD) as a preoperative management facility have been published. OBJECTIVE: The objective was to evaluate a store-and-forward TD (SFTD) system aimed at the presurgical management of nonmelanoma skin cancer patients. METHODS AND MATERIAL... ( view more )S: This was a multicenter, longitudinal, descriptive, and evaluative pilot study. Patients included in the TD-based surgical referral system presented with a nonmelanoma skin cancer or a fast-growth vascular tumor suitable for surgery under local anesthesia. Waiting intervals and on-the-day cancellation rates were evaluated and compared with a sample of patients managed through the conventional system. The accuracy of the diagnoses yielded and of the surgical techniques planned through teleconsultation was also calculated. RESULTS: A total of 134 patients were enrolled in the study. The mean waiting interval was 26.10 days [95% confidence interval (CI), 24.51-27.70] in patients managed through TD and 60.57 days (95% CI, 56.20-64.93 days; n=92; p < .001) in the conventional system. On-the-day surgery cancellation was 2.99% (95% CI, 1.52%-4.46%) for the TD series and 8.85% (95% CI, 5.62%-11.81%; p<.005) in the conventional system. The accuracy of the telediagnoses was kappa=0.86 (95% CI, 0.83-0.89). The agreement rate between the surgical technique planned through teleconsultation and the technique finally performed was kappa=0.75 (95% CI, 0.04-0.79). CONCLUSION: SFTD has been demonstrated to be effective and accurate as a preoperative tool for nonmelanoma skin cancer, avoiding unnecessary visits to the hospital and shortening the waiting intervals to the surgical treatment. ( view less ) María Elena Calderón-Segura,Sandra Gómez-Arroyo,Bertha Molina-Alvarez,Rafael Villalobos-Pietrini,Carmen Calderón-Ezquerro,Josefina Cortés-Eslava,Pedro Rafael Valencia-Quintana,Lucina López-González,Rubén Zúñiga-Reyes,José Sánchez-Rincón Ametryn and metribuzin S-triazines derivatives and EPTC thiocarbamate are herbicides used extensively in Mexican agriculture, for example in crops such as corn, sugar cane, tomato, wheat, and beans. The present study evaluated the DNA damage and cytotoxic effects of three herbicides after metabolis... ( view more )m by Vicia faba roots in human peripheral lymphocytes using akaline single cell gel electrophoresis. Three parameters were scored as indicators of DNA damage: tail length, percentage of cells with DNA damage (with comet), and level DNA damage. The lymphocytes were treated for 2 h with 0.5-5.0 microg/ml ametryn or metribuzin and 1.5-10 microg/ml EPTC. Lymphocytes also were coincubated for 2 h with 20 microl V. faba roots extracts that had been treated for 4 h with 50-500 mg/l of the two triazines or with the thiocarbamate herbicide or with ethanol (3600 mg/l), as positive control. The lymphocytes treated with three pesticides without in vivo metabolic activation by V. faba root did not show significant differences in the mean values between genotoxic parameters compared with negative control. But when human cells were exposed to three herbicides after they had been metabolized the frequency of cell comet, tail length and level DNA damage all increased. At highest concentrations of the three herbicides produced severe DNA damage compared with S10 fraction and negative control. The linear regression analysis of the tail length values of three herbicides indicated that there was genotoxic effect concentration-response relationship with ametryn and ametribuzin but no EPTC. The ethanol induced major increase DNA damage compared with S10 fraction and the three pesticides. There were not effects in cell viability with treatment EPTC and metribuzin whether or not it had been metabolized. High concentrations of ametryn alone and after it had been metabolized decreased cell viability compared with the negative control. The results demonstrated that the three herbicides needed to be activated by the V. faba root metabolism to produce DNA damage in human peripheral lymphocyte. The alkaline comet technique is a rapid and sensitive assay, to quickly evaluate DNA damage the metabolic activation of herbicide products by V. faba root in human cells in vitro. ( view less ) María Asunción García-González,Angel Lanas,Enrique Quintero,David Nicolás,Adolfo Parra-Blanco,Mark Strunk,Rafael Benito,Miguel Angel Simón,Santos Santolaria,Federico Sopeña,Elena Piazuelo,Pilar Jiménez,Cristina Pascual,Eva Mas,Pilar Irún,Jesús Espinel,Rafael Campo,Marisa Manzano,Fernando Geijo,Maria Pellisé,Ferrán González-Huix,Miguel Nieto,Jorge Espinós,Llúcia Titó,Luis Bujanda,Manuel Zaballa,Spanish Gastroenterological Association AEG  BACKGROUND AND AIMS: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection ... ( view more )and host genetic factors on GC susceptibility in a population of Spanish white GC patients. METHODS: DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology. RESULTS: Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77-3.66), smoking habit (OR 1.91, 95% CI 1.25-2.93), and positive family history of GC (OR 3.67, 95% CI 2.01-6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls. CONCLUSIONS: Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported. ( view less ) Richart J Mejías,Carlos A Yánez,Raphael Arias,Rafael A Mejías,Zaida C de Arias,José Rafael LunaThe highest number of accidents caused by scorpion stings in Mérida State, Venezuela, are caused by the genus Tityus. This study intended to find epidemic data on the occurrence of scorpionism in the Sanitary Districts of the State from 1994 to 2003. The data were gathered from the records of the E... ( view more )pidemiologic Coordination of the region. The monthly mortality EPI15 and mortality EPI13, respectively, were reviewed and evaluated. The data demonstrated that the highest incidence was registered in the Tovar, Vigía and Mérida districts. Eleven fatal accidents were recorded only in the Tovar and Vigía districts. All fatalities (100%) involved children younger than ten years of age. The authors suspect that all of the cases could be caused by the Tityus zulianus scorpion, which is the most abundant species in the region. ( view less ) María D Gutiérrez-Valero,M Luz Godino-Salido,Paloma Arranz-Mascarós,Rafael López-Garzón,Rafael Cuesta,Javier García-Martín The adsorption of five Nalpha-substituted amino acids with a 5-nitroso-6-oxo pyrimidine as substituent on a commercial activated carbon (AC) has been studied in aqueous solution at several pH values. The adsorption processes of these organic compounds have been analyzed on the basis of the electrol... ( view more )ytic behavior of the adsorbates. In all cases, the adsorption process is highly irreversible due to strong pi-pi interactions between the arene centers of the AC and the pyrimidine residue of the adsorbates. This interaction is consistent with XPS data and HOMO-LUMO theoretical calculations. The adsorption of these organic compounds provides a new route for the functionalization of the AC surface with carboxyl groups. In addition, the adsorption capacity of the AC/organic compound systems for Cu(II) ions in aqueous solution has been studied at different pH values. These systems show an increase of the adsorption capacity for Cu(II) compared to the AC, which is related to the AC functionalization with carboxyl groups due to the adsorbed organic compounds. ( view less ) Eduardo López-Laso,Rafael Camino,Maria Elena Mateos,Juan Luis Pérez-Navero,Juan José Ochoa,José Ignacio Lao-Villadóniga,Aida Ormazabal,Rafael ArtuchWe report on a GTP cyclohydrolase 1 mutation-confirmed heterozygous case presenting with an infantile hypokinetic rigid syndrome and delay in attainment of motor milestones starting from the first year of life. He had a family history of dopa-responsive dystonia-parkinsonism. CSF neopterin, biopter... ( view more )in and HVA values were decreased. Molecular study of GCH-1 gene showed the Q89X mutation in exon 1. Treatment with l-dopa resulted in a complete remission of symptoms. ( view less ) Carlos Camps,Rafael Sirera,Vega Iranzo,Miquel Tarón,Rafael Rosell Platinum compounds play a central role in cancer chemotherapy. Although treatment is limited by side effects, they continue to have widespread application. One of the main aims of clinical or translational research in cancer is the search for genetic factors that could foresee treatment outcomes, i... ( view more )n biologic activity and toxic effects. This genetic analysis might allow selection of patients who will have the greatest benefit from chemotherapy. Furthermore, a better knowledge of the underlying molecular profile of the host and the tumor will facilitate screening for lung cancer susceptibility and tailoring of chemotherapy in individual patients, choosing those most likely to respond, adjusting doses more precisely in order to reduce less adverse effects, and establishing safety profiles based on individual genetic analyses. Herein, we discuss current knowledge regarding gene expression and polymorphisms of DNA repair enzymes in regard to cancer susceptibility and response to chemotherapy. ( view less )
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