Assessing the Effect of Oxytetracycline on the Selection of Resistant Escherichia coli in Treated and Untreated Broiler Chickens.

Oxytetracycline (OTC) is administered in the poultry industry for the treatment of digestive and respiratory diseases. The use of OTC may contribute to the selection of resistant bacteria in the gastrointestinal tract of birds or in the environment. To determine the effect of OTC on the selection of resistant Escherichia coli strains post-treatment, bacteria were isolated from droppings and litter sampled from untreated and treated birds. Bacterial susceptibility to tetracyclines was determined by the Kirby-Bauer test. A total of 187 resistant isolates were analyzed for the presence of tet(A), (B), (C), (D), (E), and (M) genes by PCR. Fifty-four strains were analyzed by PFGE for subtyping. The proportion of tetracycline-resistant E. coli strains isolated was 42.88%. The susceptibility of the strains was treatment-dependent. A high clonal diversity was observed, with the tet(A) gene being the most prevalent, followed by tet(C). Even at therapeutic doses, there is selection pressure on resistant E. coli strains. The most prevalent resistance genes were tet(A) and tet(C), which could suggest that one of the main mechanisms of resistance of E. coli to tetracyclines is through active efflux pumps.

Ligand influence in electrocatalytic properties of Cu(II) triazole complexes for hydrogen peroxide detection in aqueous media.

In this work, electrocatalytic changes of Cu(II) triazole complexes (Cu(L)2) resulting from inductive effects were evaluated to fabricate a sensor for hydrogen peroxide (H2O2) determination. Three copper(II) complexes with electronically differentiated ligands were synthesized by slow diffusion method and characterized by X-ray crystallography, Fourier transformed infrared (FTIR), UV-Vis, scanning electron microscopy (SEM) and voltammetry cyclic (CV). Cu(LOMe)2/GC, Cu(LBr)2/GC and Cu(LNO2)2/GC sensors were then prepared. Under optimal conditions (pH = 11), the optimal sensor presented a response at -0.5 V, good linear range of 1-32 µM, reproducibility (1.7%), repeatability (1.2%), LOD of 0.0246 µM (S/N = 5), LOQ of 0.0747 µM (S/N = 5) and selectivity. Additionally, Cu(LNO2)2/GC sensor has been successfully applied in commercial substances, such as mouthwash, milk and tea.

Usefulness of an in vitro-transcribed RNA control for the detection and quantification of Yellow fever virus through real-time reverse transcription-polymerase chain reaction.

INTRODUCTION: Unvaccinated individuals in endemic areas with proven enzootic transmission of Yellow fever virus are at risk of infection due to a dramatic shift in the epidemiology of the disease over recent years. For this reason, epidemiological surveillance and laboratory confirmation of cases have become mandatory. OBJECTIVE: To develop and test a control RNA for YFV detection through real-time RT-PCR. METHODS: A 437-bp insert containing the T7 promoter and the target sequences for two different in-house protocols was designed in the context of the pUC57 vector and obtained through gene synthesis. After T7-driven in vitro transcription, standard curves were developed for Log10 serial dilutions of the YFV control RNA with 8 replicates. RESULTS: A dynamic range of quantification of 10 orders of magnitude was observed with a limit of detection of 6.3 GCE/µL (95% CI, 2.6 to 139.4 GCE/µL). CONCLUSION: The plasmid construct is available for YFV molecular test validation on clinical, entomological, and epizootic samples.

The ABCDE psychological first aid intervention decreases early PTSD symptoms but does not prevent it: results of a randomized-controlled trial.

BACKGROUND: Early Psychological First Aid (PFA) has been widely recommended for preventing posttraumatic stress disorder (PTSD). However, its lack of empirical evidence of safety and effectiveness has been criticized. OBJECTIVES: To assess the effectiveness of PFA-ABCDE, an original PFA protocol, for preventing PTSD one month after the intervention and decreasing PTSD symptoms at one and six months of follow up. METHODS: We assessed the eligibility of 1,140 adult survivors of recent trauma (≤ 72 hours) consulting five emergency departments in Chile. Two hundred twenty-one were randomized to receive either PFA-ABCDE (active listening, breathing retraining, categorization of needs, referral to ancillary services, and psychoeducation) or only psychoeducation. We used the Composite International Diagnostic Interview (CIDI) to assess PTSD diagnosis. The Posttraumatic Checklist (PCL), the Beck Depression Inventory-II (BDI-II), and a 0-10 points analogue visual scale were used to assess PTSD symptoms, depressive symptoms, and immediate distress relief after the intervention. RESULTS: We found no difference between the experimental and control groups in the frequency of PTSD one month after the intervention (PFA-ABCDE = 23/76 [30.3%], psychoeducation = 18/75 [24.0%], adjusted odds ratio = 1.39, 95% confidence interval = 0.63-3.07, p = .408). Immediately after the intervention, participants who received PFA-ABCDE reported greater distress relief (PFA-ABCDE mean = 9.06, psychoeducation mean = 8.55, Cohen's d = 0.30, p = .038). Fewer PTSD symptoms were reported by those who received PFA-ABCDE one month after the intervention (PFA-ABCDE mean = 36.26, psychoeducation mean = 43.62, Cohen's d = 0.42, p = .033). We found no difference in depressive symptoms at one-month follow up (p = .713) nor in PTSD symptoms six months after the intervention (p = .986). CONCLUSIONS: PFA-ABCDE does not prevent PTSD diagnosis, but it provides immediate distress relief and decreases PTSD symptoms in the short term.

Antecedentes: Los Primeros Auxilios Psicológicos (PAP) han sido recomendados para prevenir el Trastorno de Estrés Postraumático (TEPT) en supervivientes de trauma. A pesar de su popularidad, la escasez de evidencia empírica sobre su seguridad y efectividad ha sido criticada.Objetivos: Evaluar la efectividad de los PAP-ABCDE, un protocolo original de PAP, para prevenir el TEPT al mes de seguimiento y disminuir los síntomas de TEPT luego de uno y seis meses de seguimiento.Métodos: Evaluamos elegibilidad de 1.140 adultos supervivientes de trauma reciente (≤ 72 horas) que consultaron cinco servicios de urgencia en Chile. Doscientos veintiún fueron aleatorizados a recibir PAP-ABCDE (escucha activa, reentrenamiento de la respiración, categorización de necesidades, derivación a redes de apoyo, y psicoeducación) o sólo psicoeducación. Utilizamos la Composite International Diagnostic Interview (CIDI) para evaluar el diagnóstico de TEPT. La Posttraumatic Checklist (PCL), la Beck Depression Inventory-II (BDI-II), y una escala visual análoga de 0-10 puntos fueron utilizadas para evaluar síntomas de TEPT, síntomas depresivos, y alivio inmediato de distrés luego de la intervención.Resultados: No encontramos diferencia entre el grupo experimental y el grupo control en la frecuencia de TEPT un mes después de la intervención (PAP-ABCDE = 23/76 [30,3%], psicoeducación = 18/75 [24,0%], odds ratio ajustado = 1,39, intervalo de confianza 95% = 0,63-3,07, p = ,408). Inmediatamente después de la intervención los participantes que recibieron PAP-ABCDE reportaron un mayor alivio de distrés (media en PAP = 9,06, media en psicoeducación = 8,55, d de Cohen = 0,30, p = ,038). Menos síntomas de TEPT fueron reportados un mes después de la intervención por aquellos que recibieron PAP-ABCDE (media de PAP-ABCDE = 36,26, media de psicoeducación = 43,62, d de Cohen = 0,42, p = ,033). No encontramos diferencias en síntomas depresivos al mes de seguimiento (p = ,713) ni en síntomas de TEPT seis meses después de la intervención (p = ,986).Conclusiones: Los PAP-ABCDE no previenen el diagnóstico de TEPT, pero brindan alivio inmediato del distrés y disminuyen la severidad de los síntomas del TEPT en el corto plazo.

Nursing students' experiences of mental wellness during the COVID-19 pandemic: A phenomenological study.

Introduction: Acute psychological stress is commonly experienced by university students as they transition through a new learning environment; however, uncontrolled and long-term stress, such as that experienced due to the global respiratory pandemic, contributes to a severe decline in the physical and mental health of nursing students and decreases their academic success. The aim of this study was to investigate the experience of mental wellness as lived by nursing students and to understand how nursing students were coping with the impact of COVID-19. Methods: Individual interviews were used as a data collection method in this qualitative study, guided by descriptive phenomenology. Nursing students from two institutions in Western Canada were recruited in the fall of 2020. Interviews with six participants were recorded and transcribed verbatim. Meaning units from the data were transformed into a constituents table which resulted in a rich description of the essence of mental wellness as experienced by participants. Results: Key elements of the experience included: shifting support systems, disconnection, worry, sense of missing out, environmental stress and continual adaptation. The essence of the experience reflected on-going trauma. Discussion: This research highlighted the importance of acknowledging the persistent, collective trauma experienced by students and faculty alike due to the global pandemic. A trauma-informed approach to nursing education, where positive coping is modelled and a safe learning space is provided, will be required going forward.

Use of Polyhedral Oligomeric Silsesquioxane (POSS) in Drug Delivery, Photodynamic Therapy and Bioimaging.

Polyhedral oligomeric silsesquioxanes (POSS) have attracted considerable attention in the design of novel organic-inorganic hybrid materials with high performance capabilities. Features such as their well-defined nanoscale structure, chemical tunability, and biocompatibility make POSS an ideal building block to fabricate hybrid materials for biomedical applications. This review highlights recent advances in the application of POSS-based hybrid materials, with particular emphasis on drug delivery, photodynamic therapy and bioimaging. The design and synthesis of POSS-based materials is described, along with the current methods for controlling their chemical functionalization for biomedical applications. We summarize the advantages of using POSS for several drug delivery applications. We also describe the current progress on using POSS-based materials to improve photodynamic therapies. The use of POSS for delivery of contrast agents or as a passivating agent for nanoprobes is also summarized. We envision that POSS-based hybrid materials have great potential for a variety of biomedical applications including drug delivery, photodynamic therapy and bioimaging.

Evaluation of Polyhedral Oligomeric Silsesquioxane Porphyrin Derivatives on Photodynamic Therapy.

Polyhedral oligomeric silsesquioxane (POSS) is a promising scaffold to be used as delivery system. POSS can modify the properties of photosensitizers to enhance their efficacy toward photodynamic therapy (PDT). In this work, we designed, synthesized and characterized five different POSS porphyrin (POSSPs 1-5) derivatives containing hydrophobic (1-3) and hydrophilic (4 and 5) functional groups. In general, all the POSSPs showed a better singlet oxygen quantum yield than the parent porphyrins due to the steric hindrance from the POSS unique structure. POSSPs 1 and 3 containing isobutyl groups showed better PDT performance in cancer cells at lower concentrations than POSSPs 4 and 5. However; at higher concentrations, the POSSP4 containing hydrophilic groups has an enhanced PDT efficiency as compared with the parent porphyrin. We envision that the chemical tunability of POSSs can be used as a promising option to improve the delivery and performance of photosensitizers.

Design Thinking na Reestruturação do Sistema de Avaliação de Disciplina em um Curso de Medicina / Design Thinking in Restructuring the Assessment System of a Medical Course Discipline

Resumo: Introdução: A construção de conhecimento é facilitada pela utilização de metodologias inovadoras, centradas no estudante e que lhes permitam participar da elaboração de propostas para soluções de problemas reais. O design thinking (DT) é um processo que propõe a busca, de forma empática, colaborativa e criativa, de soluções para problemas complexos. Neste relato de experiência, aplicou-se o DT à educação médica como um recurso para que a comunidade acadêmica participasse diretamente da qualificação do ensino. Método: Trata-se de relato de experiência com a utilização do DT na reestruturação do sistema de avaliação de uma disciplina em um curso de graduação em Medicina. Resultado: Foi possível viabilizar soluções a partir da prototipagem, de maneira compartilhada e colaborativa, que resultaram na otimização da qualidade do processo avaliativo da disciplina, com a adoção de novos métodos. Conclusão: O DT aplicado ao campo da educação médica permitiu a reflexão sobre um processo inovador e a operacionalização dele na reestruturação da avaliação do conteúdo programático de uma disciplina no curso de graduação em Medicina.

Abstract: Introduction: Innovative, student-centered methodologies help knowledge construction, allowing students to participate in developing proposed solutions for real problems. Design thinking (DT) is a process that searches for complex problems solutions in an empathetic, collaborative, and creative way. In our report, DT was applied to medical education, as a strategy for the academic community to participate directly qualifying the training. Method: We used the DT process in an experience report to restructure the assessment system used in a discipline of a medical course. Results: A shared and collaborative form of prototyping allowed for the identification of solutions that resulted in optimized quality of the assessment process of the discipline, with the adoption of new methods. Conclusions: DT applied to the field of medical education allows one to reflect on and operationalize an innovative process in the restructuring of the evaluation of the programmatic content of a discipline in the undergraduate medical course.

Cuidado resolutivo de paracoccidioidomicose em uma Unidade Básica de Saúde. Relato de caso / Resolutive care of paracoccidioidomycosis in a Basic Health Unit. Case report / Resolución de paracoccidioidomicosis en una Unidad Básica de Salud. Relato de caso

A paracoccidioidomicose é uma micose sistêmica endêmica nas regiões tropicais da América do Sul, sendo comum no Brasil. É causada pelo fungo Paracoccidioides brasiliensis, que infecta o homem pela via respiratória por meio de inalação. Após a sintomatologia pulmonar, por disseminação hematogênica, pode acometer vários órgãos e sistemas. Uma das dificuldades no diagnóstico dessa doença se deve à sua semelhança clínica com a tuberculose. Clinicamente, a doença pode apresentar-se nas formas crônica e aguda/subaguda. Constitui-se em um importante problema de saúde pública, pois é uma doença incapacitante, podendo levar o portador ao óbito. Descreve-se, neste artigo, um caso de paracoccidioidomicose em indivíduo do sexo masculino, cuja resolutividade do cuidado pela equipe da Unidade Básica de Saúde (UBS) foi fundamental para o sucesso do tratamento e para o bom prognóstico.

Paracoccidioidomycosis is an endemic systemic mycosis in the tropical regions of South America, being common in Brazil. It is caused by the fungus Paracoccidiodes brasiliensis, which infects humans via the respiratory system through inhalation. After pulmonary symptomatology, by hematogenous dissemination, it can affect several organs and systems. One of the difficulties in the diagnosis of this disease is due to its clinical similarity with tuberculosis. Clinically, the disease may present in chronic and acute/subacute forms. It is an important public health problem, because is an incapacitating disease, which can lead the patient to death. This paper describes a case of paracoccidioidomycosis in a male patient, whose resolution of care by the Basic Health Unit (UBS) was fundamental to the success of the treatment and to the good prognosis.

La paracoccidioidomicosis es una micosis sistémica endémica en las regiones tropicales de América del Sur, siendo común en Brasil. Es causada por el hongo Paracoccidiodes brasiliensis, que infecta al hombre por la vía respiratoria por inhalación. Después de la sintomatología pulmonar, por diseminación hematógena, puede acometer varios órganos y sistemas. Una de las dificultades en el diagnóstico de esta enfermedad se debe a su semejanza clínica con la tuberculosis. Clínicamente, la enfermedad puede presentarse en las formas crónica y aguda/subaguda. Se constituye un importante problema de salud pública debido a su potencial incapacitante, pudiendo llevar al portador al óbito. Se describe en este artículo un caso de paracoccidioidomicosis en usuario del sexo masculino, cuya resolución del cuidado por el equipo de la Unidad Básica de Salud (UBS) ha sido fundamental para el éxito del tratamiento y para el buen pronóstico.

Síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) atípico por carbamazepina, a propósito de un caso pediátrico / Drug sensitivity syndrome with eosinophilia and atypical symptoms (DRESS) by carbamazepine: a case report

Introducción: El síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) generalmente es acompañado por eosinofilia. Es una enfermedad que pone en peligro la vida del paciente. Se presenta como reacción adversa a infecciones y a medicamentos, usualmente asociada al uso de antiepilépticos. Caso clínico: Paciente de 6 años, masculino, con antecedente de Epilepsia de reciente diagnóstico, que consultó en Servicio de Urgencias dos semanas después de iniciar tratamiento con Carbamazepina, por cuadro caracterizado por eritema de predominio facial, exacerbado con la exposición al sol. Posteriormente presentó fiebre con episodios hasta 40 °C, que se asoció a convulsiones. Después de un exhaustivo estudio se concluyó DRESS atípico (sin eosinofilia), iniciando tratamiento corticoideo con favorable respuesta clínica. Discusión: El síndrome de DRESS, es una enfermedad de difícil diagnóstico por sus múltiples diagnósticos diferenciales y falta de criterios diagnósticos. Es esencial la suspensión inmediata del fármaco causante, para evitar progresión de la enfermedad e iniciar tratamiento precoz.

Background: The drug sensitivity syndrome with eosinophilia and systemic symptoms (DRESS) is usually accompanied by eosinophilia. It is a disease that endangers the life of the patient. It occurs as an adverse reaction to infections and medications, usually associated with the use of antiepileptics. Case report: A 6-year-old patient, male, with a recent diagnosis of epilepsy, who consulted the Emergency Department two weeks after initiating treatment with Carbamazepine because of a condition characterized by facial predominance erythema, exacerbated by sun exposition. Subsequently presented fever with episodes up to 40 ° C, which was associated with seizures. After an exhaustive study, atypical DRESS syndrome (without eosinophilia) was made, initiating corticoid treatment with favorable clinical response. Discussion: DRESS syndrome is a disease difficult to diagnose because of its multiple differential diagnoses and lack of diagnostic criteria. Immediate suspension of the causative drug is essential to prevent progression of the disease and initiate early treatment Keywords: Drug Hypersensitivity Syndrome, Carbamazepine, Corticoid.

Hipercromia pós-inflamatória associada à psoríase. Relato de caso / Post-inflammatory hyperchromia associated with psoriasis. Case report

A Hipercromia pós-inflamatória (HPI), desordem de pigmentação da pele decorrente da produção exagerada de melanina, apresenta-se sob a forma de manchas hipercrômicas e representa uma sequela importante da psoríase, uma dermatose inflamatória. Objetiva-se, neste artigo, um relato de caso, descrever a HPI surgida após um quadro de psoríase, em paciente do gênero masculino, 54 anos de idade, cor parda, marceneiro de profissão, sem histórico de tabagismo, obesidade ou doença de base, atendido em uma Unidade Estratégia Saúde da Família (ESF), no município de Vassouras, região Centro Sul do Estado do Rio de Janeiro. A psoríase é uma doença imunológica crônica, resultante da estimulação persistente de células T por imunógenos de origem epidérmica, envolvendo a imunidade inata e a adquirida. A conduta terapêutica da HPI incluiu a prescrição de corticosteróides, despigmentantes e fotoprotetores. O acompanhamento do paciente por psicoterapia do Núcleo de Apoio à Saúde da Família (NASF), da ESF e pelo dermatologista da média complexidade da Rede de Atenção à Saúde (RAS) representou um diferencial e revelou-se imprescindível para a integralidade do cuidado em saúde.(AU)

Post-inflammatory hyperchromia (IPH), a pigmentation disorder of the skin resulting from the exaggerated production of melanin, is manifested by hyperchromic patches and is an important consequence of psoriasis, an inflammatory dermatosis. The objective of this article is to describe a case of IPH that appeared after psoriasis in a patient attended at a Family Health Strategy Unit (FHU), in the city of Vassouras, in the central region of the State of Rio de Janeiro. Psoriasis is a chronic immune disease that results from the persistent stimulation of T cells by immunogens of epidermal origin, involving innate and acquired immunity. The therapeutic management of IPH consists in prescribing of corticosteroids, despigmentants and photoprotectors. The follow-up of the patient through Psychology of the Family Health Support Center, the FHU and the dermatologist of the medium complexity of the Health Care Network represented a differential and proved to be essential for the integrality of health care.(AU)

[Management of psychological trauma in primary care]. / Trauma psicológico en la atención primaria: orientaciones de manejo.

Exposure to traumatic events is frequent in the general population and psychiatric sequelae such as post-traumatic stress disorders are common. The symptoms of psychiatric sequelae after trauma are vague, with multiple psychological and physical symptoms, which can confuse the health care professional. This paper seeks to facilitate the work in primary care, providing practical information about the diagnosis, initial management and referral of patients who have suffered traumatic experiences. Some early interventions and treatments are suggested.

Trauma psicológico en la atención primaria: orientaciones de manejo / Management of psychological trauma in primary care

Exposure to traumatic events is frequent in the general population and psychiatric sequelae such as post-traumatic stress disorders are common. The symptoms of psychiatric sequelae after trauma are vague, with multiple psychological and physical symptoms, which can confuse the health care professional. This paper seeks to facilitate the work in primary care, providing practical information about the diagnosis, initial management and referral of patients who have suffered traumatic experiences. Some early interventions and treatments are suggested.

[Proposal to address the mental health problems detected after the February 27, 2010 earthquake]. / Propuesta para abordar los problemas de salud mental detectados en el proceso diagnóstico de la Delegación Presidencial para la reconstrucción tras el terremoto del 27 de febrero de 2010.

One of the most important topics mentioned by people from places affected by the February 27th, 2010 earthquake to the Presidential Delegation for the Reconstruction, was the urgent need of mental health care. Given the enormous individual and social burden of mental health sequelae after disasters, its treatment becomes a critical issue. In this article, we propose several actions to be implemented in Chile in the context of the process of recovery and reconstruction, including optimization of social communication and media response to disasters; designing and deployment of a national strategy for volunteer service; training of primary care staff in screening and initial management of post-traumatic stress reactions; and training, continuous education and clinical supervision of a critical number of therapists in evidence-based therapies for conditions specifically related to stress.

Propuesta para abordar los problemas de salud mental detectados en el proceso diagnóstico de la Delegación Presidencial para la reconstrucción tras el terremoto del 27 de febrero de 2010 / Proposal to address the mental health problems detected after the February 27, 2010 earthquake

One of the most important topics mentioned by people from places affected by the February 27th, 2010 earthquake to the Presidential Delegation for the Reconstruction, was the urgent need of mental health care. Given the enormous individual and social burden of mental health sequelae after disasters, its treatment becomes a critical issue. In this article, we propose several actions to be implemented in Chile in the context of the process of recovery and reconstruction, including optimization of social communication and media response to disasters; designing and deployment of a national strategy for volunteer service; training of primary care staff in screening and initial management of post-traumatic stress reactions; and training, continuous education and clinical supervision of a critical number of therapists in evidence-based therapies for conditions specifically related to stress.

Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated rats treated with lipopolysaccharide.

Sepsis progresses to multiple organ dysfunction (MOD) due to the uncontrolled release of inflammatory mediators. Carotid chemo/baro-receptors could play a protective role during sepsis. In anesthetized male rats, we measured cardiorespiratory variables and plasma TNF-α, glucocorticoids, epinephrine, and MOD marker levels 90min after lipopolysaccharide (LPS) administration in control (SHAM surgery) and bilateral carotid chemo/baro-denervated (BCN) rats. BCN prior to LPS blunted the tachypneic response and enhanced tachycardia and hypotension. BCN-LPS rats also showed blunted plasma glucocorticoid responses, boosted epinephrine and TNF-α responses, and earlier MOD onset with a lower survival time compared with SHAM-LPS rats. Consequently, the complete absence of carotid chemo/baro-sensory function modified the neural, endocrine and inflammatory responses to sepsis. Thus, carotid chemo/baro-receptors play a protective role in sepsis.

Neuroendocrine mechanisms for immune system regulation during stress in fish.

In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production.

Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy.

Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.

LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation.

Lipopolysaccharide (LPS) administered I.P. increases significantly the activation of c-Fos in neurons of the nucleus of the solitary tract (NTS), which in turn activates hypothalamus-pituitary-adrenal axis. The vagus nerve appears to play a role in conveying cytokines signals to the central nervous system (CNS), since -in rodent models of sepsis- bilateral vagotomy abolishes increases in plasmatic glucocorticoid levels, but does not suppress c-Fos NTS activation. Considering that NTS also receives sensory inputs from carotid body chemoreceptors, we evaluated c-Fos activation and plasmatic cortisol levels 90 min after I.P. administration of 15 mg/kg LPS. Experiments were performed in male Sprague-Dawley rats, in control conditions and after bilateral carotid neurotomy (BCN). LPS administration significantly increases the number of c-Fos positive NTS neurons and plasmatic cortisol levels in animals with intact carotid/sinus nerves. When LPS was injected after BCN, the number of c-Fos positive NTS neurons, and plasmatic cortisol levels were not significantly modified. Our data suggest that carotid body chemoreceptors might mediate CNS activation during sepsis.

Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome.

In addition to their role in cardiorespiratory regulation, carotid body (CB) chemoreceptors serve as sensors for inflammatory status and as a protective factor during sepsis. However, lipopolysaccharide-induced sepsis (LPS) reduces CB responsiveness to excitatory or depressant stimuli. We tested whether LPS exerts a direct effect on the carotid chemoreceptor pathway, the CB and its sensory ganglion. We determined that the rat CB and nodose-petrosal-jugular ganglion complex (NPJgc) express TLR4, TNF-α and its receptors (TNF-R1 and TNF-R2). LPS administration (15mg/kg intraperitoneally) evoked MyD88-mechanism pathway activation in CB and NPJgc, with NF-κB p65, p38 MAPK, and ERK activation. Consistently, LPS increased TNF-α and TNF-R2. Double-labeling studies showed that the aforementioned pathway occurs in TH-containing glomus cells and NPJgc neurons, components of the chemosensitive neural pathway. Thus, our results suggest that LPS acting directly through TLR4/MyD88-mechanism pathways increases TNF-α and TNF-R2 expression in the carotid chemoreceptor pathway. These results show a novel afferent pathway to the central nervous system during endotoxemia, and could be relevant in understanding sepsis pathophysiology and therapy.