Uso de emulsiones lipídicas en intoxicación por antidepresivos tricíclicos desde elservicio de urgencias: Una serie de casos / Use of lipid emulsions in tricyclic antidepressant intoxication from the emergency department: A series of cases

Se describen a continuación una serie de casos clínicos de dos pacientes que ingresan por el servicio de urgencias con antecedente de trastorno depresivo, los cuales presentan ingesta voluntaria de medicamentos con intención suicida. Ambas con cuadro clínico de envenenamiento por antidepresivos tricíclicos, con síntomas anticolinérgicos, compromiso neurológico y cardiotoxicidad. Se indica tratamiento dirigido a la intoxicación aguda, medidas de descontaminación y como última instancia se emplean emulsiones lipídicas por la refractariedad del cuadro basados en algunos reportes de literatura que soportan uso de estas emulsiones en intoxicaciones diferentes a anestésicos locales logrando desenlaces favorables en ambos casos. (AU)

A series of clinical cases of two patients admitted to the emergency department with a history of depressive disorder is described below, both of whom have voluntarily ingested drugs with suicidal intent. Both with clinical form of tricyclic antidepressant poisoning, with anticholinergic symptoms, neurological compromise and cardiotoxicity. Treatment directed to acute intoxication, decontamination measures are indicated and as a last resource, lipid emulsions are used due to the refractoriness of the case based on some literature reports that support the use of these emulsions in other poisonings than local anesthetics, achieving favorable outcomes in both cases. (AU)

Características de los pacientes adultos con neutropenia febril en un hospital universitario (Medellín, 2012-2016) / Characteristics of adult patients with febrile neutropenia in a university hospital (Medellin, 2012-2016) / Características dos pacientes adultos com neutropenia febril em um hospital universitário (Medellín, 2012-2016)

Objetivo: la neutropenia febril es una urgencia médica que se presenta frecuentemente en pacientes con inmunosupresión asociada a tratamientos oncológicos, que aumenta el riesgo de complicaciones infecciosas y de morir. El objetivo de esta investigación es describir las características clínicas, microbiológicas y pronósticas de los pacientes con neutropenia febril en un hospital universitario. Metodología: estudio observacional descriptivo, entre enero de 2012 y junio de 2016, en pacientes con diagnóstico de neutropenia febril (neutrófilos menores de 500 cel/mm, temperatura mayor de 38 °C) hospitalizados en el Hospital Pablo Tobón Uribe de Medellín, Colombia. Resultados: se evaluaron 226 pacientes con neutropenia febril, de los que el 96% tenía enfermedad oncológica de base. Las principales fuentes de infección fueron la piel y el tracto gastrointestinal. Del total de los hemocultivos, el 31% fue positivo. El principal aislamiento fue Escherichia coli (E. coli) y la mortalidad hospitalaria fue del 17%. Conclusiones: las características clínicas de la población fueron similares a las de la literatura internacional. Se encontraron algunas discrepancias en cuanto a epidemiología de los microorganismos aislados, resistencia microbiana y mortalidad. Solo un tercio de los pacientes presentó bacteriemia, E. coli sigue siendo el principal patógeno.

Objective: Febrile neutropenia is a condition present in patients with some degree of immunosuppression associated to oncology treatment, which leads to risks of infectious complications and death. The aim of this research is to describe the clinical, microbiological and prognostic characteristics in patients with febrile neutropenia in a university hospital. Methodology: Retrospective cohort study developed between January of 2012 and June of 2016 in patients with febrile neutropenia (neutrophils <500 cell/mm, temperature >38.3 °C), who were hospitalized in the Pablo Tobon Uribe Hospital of Medellin, Colombia. Results: 226 patients were evaluated, 96% of who had an oncological diagnostic. The main infectious sources were the skin and the gastrointestinal tract. Blood cultures were positive in 31%. The main pathogen was Escherichia coli in 26% and the overall hospital mortality rate was 17%. Conclusions: The clinical characteristics of our population were similar to the national and international reports, but we found epidemiological differences in microbiological agents, bacterial resistance and mortality. Only one third of the patients presented bacteremia. E. coli remains the main pathogen involved.

Objetivo: a neutropenia febril é uma urgência médica que se apresenta frequentemente em pacientes com imunossupressão associada a tratamentos oncológicos, que aumenta o risco de complicações infecciosas e de morte. O objetivo desta investigação é descrever as características clínicas, microbiológicas e prognósticas dos pacientes com neutropenia febril em um hospital universitário. Metodologia: estudo observacional descritivo, entre janeiro de 2012 e junho de 2016, em pacientes com diagnóstico de neutropenia febril (neutrófilos menores de 500 cel/mm, temperatura maior de 38 °C) hospitalizados no Hospital Pablo Tobón Uribe de Medellín, Colômbia. Resultados: se avaliaram 226 pacientes com neutropenia febril, dos quais, 96% tinha doença oncológica de base. As principais fontes de infecção foram a pele e o trato gastrointestinal. Do total das hemoculturas, 31% foi positivo. O principal isolamento foi Escherichia coli (E. coli) e a mortalidade hospitalar foi de 17%. Conclusões: as características clínicas da população foram similares às da literatura internacional. Se encontraram algumas discrepâncias em quanto a epidemiologia dos microrganismos isolados, resistência microbiana e mortalidade. Só um terço dos pacientes apresentou bacteriemia, E. coli segue sendo o principal patógeno.

Uso de inhibidores de la bomba de protones en Atención Primaria ¿correcto? / Use of proton pump inhibitors in primary care. Always right?

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Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1ß and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1ß and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1ß and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.

Short- and long-term consequences of perinatal asphyxia: looking for neuroprotective strategies.

Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. A primary insult is first produced by the length of the time without oxygenation, leading to hypoxia/ischemia and death if oxygenation is not promptly established. A second insult is produced by re-oxygenation, eliciting a cascade of biochemical events for restoring function, implying, however, improper homeostasis. The effects observed long after perinatal asphyxia can be explained by over-expression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for oxidised nicotinamide adenine dinucleotide (NAD(+)) during re-oxygenation. Asphyxia also induces transcriptional activation of pro-inflammatory factors, including nuclear factor κB (NFκB) and its subunit p65, whose translocation to the nucleus is significantly increased in brain tissue from asphyxia-exposed animals, in tandem with PARP-1 overactivation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. It is proposed that PARP-1 inhibition also down-regulates the expression of pro-inflammatory cytokines.Nicotinamide is a suitable PARP-1 inhibitor, whose effects have been studied in an experimental model of global perinatal asphyxia in rats, inducing the insult by immersing rat foetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, immediately treated, or given to surrogate dams for nursing, pending further experiments. Systemic administration of nicotinamide 1 h after the insult inhibited PARP-1 overactivity in peripheral and brain tissue, preventing several of the long-term consequences elicited by perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles.

Flavodoxin overexpression confers tolerance to oxidative stress in beneficial soil bacteria and improves survival in the presence of the herbicides paraquat and atrazine.

AIM: To determine whether expression of a cyanobacterial flavodoxin in soil bacteria of agronomic interest confers protection against the widely used herbicides paraquat and atrazine. METHODS AND RESULTS: The model bacterium Escherichia coli, the symbiotic nitrogen-fixing bacterium Ensifer meliloti and the plant growth-promoting rhizobacterium Pseudomonas fluorescens Aur6 were transformed with expression vectors containing the flavodoxin gene of Anabaena variabilis. Expression of the cyanobacterial protein was confirmed by Western blot. Bacterial tolerance to oxidative stress was tested in solid medium supplemented with hydrogen peroxide, paraquat or atrazine. In all three bacterial strains, flavodoxin expression enhanced tolerance to the oxidative stress provoked by hydrogen peroxide and by the reactive oxygen species-inducing herbicides, witnessed by the enhanced survival of the transformed bacteria in the presence of these oxidizing agents. CONCLUSIONS: Flavodoxin overexpression in beneficial soil bacteria confers tolerance to oxidative stress and improves their survival in the presence of the herbicides paraquat and atrazine. Flavodoxin could be considered as a general antioxidant resource to face oxidative challenges in different micro-organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of plant growth-promoting rhizobacteria or nitrogen-fixing bacteria with enhanced tolerance to oxidative stress in contaminated soils is of significant agronomic interest. The enhanced tolerance of flavodoxin-expressing bacteria to atrazine and paraquat points to potential applications in herbicide-treated soils.

Effects of salt stress and rhizobial inoculation on growth and nitrogen fixation of three peanut cultivars.

Increasing soil salinity represents a major constraint for agriculture in arid and semi-arid lands, where mineral nitrogen (N) deficiency is also a frequent characteristic of soils. Biological N fixation by legumes may constitute a sustainable alternative to chemical fertilisation in salinity-affected areas, provided that adapted cultivars and inoculants are available. Here, the performance of three peanut cultivars nodulated with two different rhizobial strains that differ in their salt tolerance was evaluated under moderately saline water irrigation and compared with that of N-fertilised plants. Shoot weight was used as an indicator of yield. Under non-saline conditions, higher yields were obtained using N fertilisation rather than inoculation for all the varieties tested. However, under salt stress, the yield of inoculated plants became comparable to that of N-fertilised plants, with minor differences depending on the peanut cultivar and rhizobial strain. Our results indicate that N fixation might represent an economical, competitive and environmentally friendly choice with respect to mineral N fertilisation for peanut cultivation under moderate saline conditions.

Uveal inflammation in septic newborn foals.

BACKGROUND: Septicemia in humans is described as a leading cause of uveitis, which eventually can induce blindness. HYPOTHESIS/OBJECTIVES: Uveal inflammatory findings could be related to sepsis severity in newborn foals and might be used as an indirect indicator for survival. ANIMALS: Seventy-four septic foals, 54 nonseptic foals, and 42 healthy foals. METHODS: Prospective observational clinical study. A detailed blinded, ophthalmic examination was performed by boarded ophthalmologists on all admitted newborn foals. Foals were grouped as septic (when blood culture resulted positive or the sepsis score was > or =14), nonseptic, and controls. Based on blood culture results, the septic group was subdivided into bacteremic and nonbacteremic foals. RESULTS: Blood culture was performed in 62/74 septic foals, from which 35 (56%) were bacteremic and 27 (44%) were non-bacteremic. Anterior uveitis was diagnosed in a significantly (P < .005) higher number of septic/bacteremic foals (14/35, 40%) than in septic/nonbacteremic foals (5/27, 19%), nonseptic foals (4/54, 7%), and control foals (0%). Anterior chamber fibrin was only observed in 4/14 (29%) septic/bacteremic foals with anterior uveitis. Anterior uveitis was also associated with posterior uveitis in 6/35 (19%) septic/bacteremic foals. The diagnosis of uveitis was related to nonsurvival (P = .001, odds ratio = 6.2, 95% confidence interval = 2.1-18.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Anterior uveitis is highly prevalent in septic newborn foals, especially in those with a positive blood culture, and it should be considered as a survival prognostic factor.

Retrobulbar dermoid cyst in a horse: a case report.

A 4-year-old Andalusian horse was presented for examination following a 3-month history of exophthalmos of the right eye and a soft swelling of the right supraorbital fossa noted after blunt head trauma. Ultrasonographic examination of the swelling showed an anecogenic mass of 5 cm in diameter involving the retrobulbar space. Centesis of the mass through the supraorbital fossa was performed and yielded a serous fluid with 7.2 g/dL of total protein and density of 1040. No cells were seen in the sample. A tentative diagnosis of cyst was made. The cyst was surgically removed and the definitive histologic diagnosis was retrobulbar dermoid cyst. No recurrence has developed 18 months following the complete removal of the cyst capsule. To the authors' knowledge, there are no previous reports of retrobulbar dermoid cysts in horses. Localization, causes and success of surgical treatment of dermoid cysts are discussed.

Transgenic Medicago truncatula plants that accumulate proline display nitrogen-fixing activity with enhanced tolerance to osmotic stress.

Legume root nodule nitrogen-fixing activity is severely affected by osmotic stress. Proline accumulation has been shown to induce tolerance to salt stress, and transgenic plants over-expressing Delta(1)-pyrroline-5-carboxylate synthetase (P5CS), which accumulates high levels of proline, display enhanced osmotolerance. Here, we transformed the model legume Medicago truncatula with the P5CS gene from Vigna aconitifolia, and nodule activity was evaluated under osmotic stress in transgenic plants that showed high proline accumulation levels. Nitrogen fixation was significantly less affected by salt treatment compared to wild-type (WT) plants. To our knowledge, this is the first time that transgenic legumes have been produced that display nitrogen-fixing activity with enhanced tolerance to osmotic stress. We studied the expression of M. truncatula proline-related endogenous genes M. truncatulaDelta(1)-pyrroline-5-carboxylate synthetase 1 (MtP5CS1), M. truncatulaDelta(1)-pyrroline-5-carboxylate synthetase 2 (MtP5CS2), M. truncatula ornithine delta-aminotransferase (MtOAT), M. truncatula proline dehydrogenase (MtProDH) and a proline transporter gene in both WT and transgenic plants. Our results indicate that proline metabolism is finely regulated in response to osmotic stress in an organ-specific manner. The transgenic model allowed us to analyse some of the biochemical and molecular mechanisms that are activated in the nodule in response to high salt conditions, and to ascertain the essential role of proline in the maintenance of nitrogen-fixing activity under osmotic stress.

Optimization of a microwave-assisted extraction method for the analysis of polycyclic aromatic hydrocarbons from fish samples.

A microwave-assisted extraction (MAE) procedure has been developed and optimized for the extraction of six regulated polycyclic aromatic hydrocarbons (PAHs) from muscle samples of polluted fish. The procedure involves the simultaneous microwave-assisted extraction of PAHs with n-hexane and the lipids hydrolysis with potassium hydroxide. Experimental design methodology allows a quick and robust optimization of operational parameters such as the extraction time, temperature, and solvent volumes. In these final optimized conditions, the procedure can be applied to a vast range of fat containing fish samples without significant changes, thus enabling its routine use. Recoveries around 90% for the studied compounds benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, and indene[1,2,3-cd]pyrene and quantification limits (between 0.07 and 0.53 ng/g dry weight) far below the regulated limits, have been obtained. The procedure is applied to several different fish samples. Further, accuracy validation using NIST SRM 2977 reference material was carried out.

Myocarditis and generalised vasculitis associated with leishmaniosis in a dog.

A three-year-old, female bulldog was presented with bilateral uveitis, apathy, listlessness, generalised lymphadenopathy and perivulvar haematoma. The initial laboratory studies showed non-regenerative anaemia, polyclonal gammopathy and a high urine protein:creatinine ratio. Serology for leishmaniosis was positive and treatment with allopurinol and meglumine antimoniate was started. Despite treatment, the dog's clinical condition deteriorated. Signs included cutaneous ecchymosis, respiratory distress and finally cardiorespiratory arrest. Histopathological studies of postmortem tissue samples revealed a generalised vasculitis of several internal organs and severe myocarditis. Leishmania species organisms were identified in affected tissues using immunoperoxidase labelling and PCR techniques.

Theoretical structure and vibrational analysis of ethyl methanesulfonate, CH3SO2OCH2CH3.

Ethyl methanesulfonate, CH3SO2OCH2CH3, is well-known as an alkylating agent in mutagenic and carcinogenic processes. Its electronic structure and that of the methanesulfonate anion (CH3SO3-) were determined using optimization methods based on density functional theory and Moller-Plesset second-order perturbation theory. For CH3SO2OCH2CH3, two conformations with symmetries C(s) and C1 are obtained, the former being more stable than the latter. Natural bond orbital (NBO) calculations show the C(s) conformation provides a more favorable geometry of the lone pairs of the oxygen atom linking the ethyl group. The NBO technique also reveals the characteristics of the methanesulfonate anion as a leaving group due to the rearrangement of the excess electronic charge after alkylation. Furthermore, the infrared spectra of CH3SO2OCH2CH3 are reported for the liquid and solid states as well as the Raman spectrum of the liquid. Comparison to experiment of the conformationally averaged IR spectrum of C(s) and C1 provides evidence of the predicted conformations in the solid IR spectrum. These experimental data along with the calculated theoretical force constants are used to define a scaled quantum mechanical force field for the target molecule, which allowed the measured frequencies to be reproduced with a final root-mean-square deviation of 9 cm(-1) and, thus, a reliable assignment of the vibrational spectrum.

La música en el trabajo de parto / Music in the work of childbirth

Este trabajo es una propuesta de apoyo al Parto Natural en el convencimiento que la parturienta que inicia relajada su Trabajo de Parto y en un lugar con ambiente sonoro controlado, íntimo, silencio y privado, necesariamente tendría un parto natural. Se aplica la Música Barroca durante la Fase latente del trabajo de parto ya que por sus nobles virtudes estéticas -auditivas y sus características técnicas- musicales, media en la relajación y bienestar de la parturienta. Se privilegia el silencio y el control del ambiente sonoro de la Sala de Parto en la Fase activa del trabajo de parto. Los fundamentos fisiológicos involucrados en la aplicación de este método, dicen relación con el ben eficio que aporta la Música Barroca al facilitar el efecto de las B-endorfinas. Por otro lado, con la eliminación de ruidos parásitos de la Sala de Partos se contribuye, además, a la eliminación de los mediadores químicos del Stress materno. Ambos acontecimientos, facilitan la armonía del eje hipotálamo - hipofisiario - adrenal materno, traduciéndose en mayor bienestar; y por extensión, mejor apego con su hijo en su condición fetal y al nacer.

Smoking-related attitudes, characteristics, and opinions in a group of young men with asthma.

UNLABELLED: The objective of this study was to examine the attitudes, characteristics, and opinions about smoking of a group of young asthmatic men. POPULATION AND METHODS: An anonymous, personal questionnaire was administered to 611 young male volunteers who had been diagnosed with asthma (according to the National Heart, Lung, and Blood Institute/World Health Organization Global Initiative for Asthma, 1995) in the respiratory disease and allergy clinics of the Burgos Military Hospital (Spain). This questionnaire contained items related to personal information, asthma characteristics, opinions about smoking, and information related to smoking habits. RESULTS: Six hundred patients with asthma completed the questionnaire. All were men, mean age 20.16 +/- 3.03 years; 189 (31.5%) were smokers and 16 (2.5%) were ex-smokers. Mean age at onset of regular smoking was 16.46 +/- 2 years. Sixty-five percent (65.07%) smoked fewer than 10 cigarettes per day. Most of the smoking asthmatics had mild asthma (58.9%). Eighty-eight percent (88.3%) had moderate dependence. Many of the smoking asthmatics were contemplating stopping smoking (54%), and 59% had tried before to stop. Concern about health was the main reason given for stopping smoking. Asthmatics who smoked had a higher percentage of smokers among family members, friends, and colleagues than nonsmoking asthmatics. Attitudes toward smoking were more permissive among smoking asthmatics. Only 36.64% of the total had received information about tobacco previously. In the sample group, 7% claimed that they did not smoke but their carbon monoxide concentration in exhaled air was 10 ppm or higher. CONCLUSIONS: There were no differences in the onset of the smoking habit between asthmatic and nonasthmatic young people. A large percentage of the smoking asthmatics were considering smoking cessation, motivated mainly by their asthma condition. The group as a whole had little previous information about tobacco.

Ras/MEK/ERK Up-regulation of the fibroblast KCa channel FIK is a common mechanism for basic fibroblast growth factor and transforming growth factor-beta suppression of myogenesis.

The 10T1/2-MRF4 fibroblast/myogenic cell system was used to address the following interrelated questions: whether distinct signaling pathways underlie myogenic inhibition by basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta; which of these pathways also up-regulates the fibroblast intermediate conductance calcium-activated potassium channel, FIK, a positive regulator of cell proliferation; and whether FIK up-regulation underlies some or all myogenic inhibitory signaling events. The results show that myogenic inhibition in 10T1/2-MRF4 cells, by both bFGF and TGF-beta, requires activation of the Ras/mitogen-activated protein (MAP) kinase/MAP kinase-ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and resultant FIK up-regulation. We show that FIK is instrumental in MEK-dependent suppression of acetylcholine receptor channel expression but that MEK activation and FIK up-regulation are not essential to suppression of myosin heavy chain and myotube formation. These data indicate that Ras/MEK/ERK induction of FIK is pivotal to regulation of certain myogenic events by both receptor tyrosine kinases and TGF-beta receptor, and this is also the first demonstration of chronic FIK up-regulation by the TGF-beta receptor family. Furthermore, the results define the physiologic signaling requirements for growth factor-stimulated FIK up-regulation, whereas previous work has concentrated on constitutive FIK up-regulation in cells stably transfected with oncoprotein signaling molecules. This study, together with earlier work showing that FIK positively regulates cell proliferation, establishes this member of the IK channel family as a multifunctional, growth factor-regulated signaling molecule.

The fibroblast intermediate conductance K(Ca) channel, FIK, as a prototype for the cell growth regulatory function of the IK channel family.

The fibroblast intermediate conductance, calcium-activated potassium channel (FIK) is proposed here as a functional prototype for other IK channels which to date have undefined physiologic actions. FIK pharmacology in the 10T1/2-MRF4 myogenic fibroblast cell line was determined: to define the relationship of FIK to other IKs; to confirm a physiologic role for FIK; and, thus develop a hypothesis about IK channel family function. Whole cell patch-clamp electrophysiology was used to determine K(0.5) values for FIK block by the structurally related peptides charybdotoxin (ChTX) (7 nm) and iberiotoxin (IbTX) (536 nm), and a new unrelated FIK inhibitor, Stichodactyla toxin (StK) (85 nm). Peptide pharmacology for FIK was consistent with that of recently cloned IKs. ChTX and StK inhibited bFGF stimulated 10T1/2-MRF4 cell proliferation with dose-dependencies consistent with their FIK blocking actions. ChTX, StK, and IbTX also evoked MRF4-dependent transcription as measured by muscle acetylcholine receptor channel functional expression; but they did not evoke subsequent multinucleated fiber formation or myosin heavy chain expression, suggesting a role for FIK in early, rather than late, myogenic events. Thus despite structural differences, ChTX, IbTX, and StK have common effects on cell growth and differentiation reflecting their common FIK blocking action. We suggest that a major function of the IK channel family is to regulate cell growth.