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Chronic stress affects millions of people around the world, and it can trigger different behavioral disorders like nociceptive hypersensitivity and anxiety, among others. However, the mechanisms underlaying these chronic stress-induced behavioral disorders have not been yet elucidated. This study was designed to understand the role of high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) in chronic stress-induced nociceptive hypersensitivity. Chronic restraint stress induced bilateral tactile allodynia, anxiety-like behaviors, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) and activation of spinal microglia. Moreover, chronic stress enhanced HMGB1 and TLR4 protein expression at the dorsal root ganglion, but not at the spinal cord. Intrathecal injection of HMGB1 or TLR4 antagonists reduced tactile allodynia and anxiety-like behaviors induced by chronic stress. Additionally, deletion of TLR4 diminished the establishment of chronic stress-induced tactile allodynia in male and female mice. Lastly, the antiallodynic effect of HMGB1 and TLR4 antagonists were similar in stressed male and female rats and mice. Our results suggest that chronic restraint stress induces nociceptive hypersensitivity, anxiety-like behaviors, and up-regulation of spinal HMGB1 and TLR4 expression. Blockade of HMGB1 and TLR4 reverses chronic restraint stress-induced nociceptive hypersensitivity and anxiety-like behaviors and restores altered HMGB1 and TLR4 expression. The antiallodynic effects of HMGB1 and TLR4 blockers in this model are sex independent. TLR4 could be a potential pharmacological target for the treatment of the nociceptive hypersensitivity associated with widespread chronic pain.
Assuntos
Proteína HMGB1 , Hiperalgesia , Animais , Feminino , Masculino , Camundongos , Ratos , Alarminas/metabolismo , Doença Crônica , Proteína HMGB1/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Nociceptividade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Medula Espinal , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Gender-based violence is a major public health concern arising from the structural discrimination of women and girls. In 2014, Ecuador criminalized acts of femicide in response to a growing crisis across the region. As no epidemiological studies on the state of female homicides and femicides have been published, we estimated patterns of female homicides and femicides nationally and the burden through economic cost per years of life lost, between 2001 and 2017. METHODS: Using aggregated data from the National Institute of Census and Statistics and police records we estimated the annual mortality rates, cumulative incidence and prevalence odds ratios for female homicides and femicides, from 2001 to 2017. The impact of aggressions, assaults and violence on years of life lost due to premature mortality was estimated using the Human Capital method. RESULTS: Over the period, at least 3236 cases of female homicides and femicides were reported. The highest murder rate occurred in the province of Sucumbíos (6.5 per 100,000) and in the Putumayo canton (12.5 per 100,000). The most common way to murder their victims was using firearms (38%). The highest odds ratio was estimated for women aged between 25 and 29, at 4.5 (3.9-5.1), of primary school attainment at 17.2 (14.6-20.3) and of Afro-Ecuadoran descent 18.1 (10.5-30.9). Female homicide-related costs reached, on average, $35 million per year and more than $500 million lost from 2001 to 2017. CONCLUSIONS: The high rates, distribution and cost indicate that investments are urgently needed to address the structural causes and reduce the impact of female homicides and femicides in Ecuador; thereby protecting the livelihood and well-being of their women and girls.
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Vítimas de Crime , Violência de Gênero , Adulto , Equador/epidemiologia , Feminino , Homicídio , Humanos , ViolênciaRESUMO
The purpose of this study was to investigate the mechanism of antiallodynic effect of tizanidine in neuropathic rats. Spinal nerve ligation reduced withdrawal threshold which was interpreted as tactile allodynia. Increasing doses of tizanidine induced a dose-dependent antiallodynic effect in nerve injured rats. Tizanidine was more effective in female than male neuropathic rats. This drug induced a lower antiallodynic effect in ovariectomized, compared with non-ovariectomized, neuropathic rats, while systemic reconstitution of estradiol (E2) levels in ovariectomized neuropathic females fully restored the antiallodynic effect of tizanidine. Naloxone reduced the antiallodynic effect of tizanidine in male but not in female neuropathic rats. Ovariectomy restored the antagonizing effect of naloxone in the antiallodynic effect of tizanidine, whereas treatment with E2 abolished the effect of naloxone on tizanidine activity. Rauwolscine (α2 antagonist) and imiloxan (α2B antagonist) completely abated tizanidine-induced antiallodynic effect in female neuropathic rats. In contrast, BRL-44408 (α2A antagonist) partially decreased the effect of tizanidine while JP-1302 (α2C antagonist) was ineffective. Rauwolscine, imiloxan and BRL-44408 decreased withdrawal threshold in naïve female rats. Rauwolscine did not modify withdrawal threshold in naïve male rats. AGN192403 (I1 antagonist), BU224 (I2 antagonist), prazosin (α1 antagonist) and methiothepin (5-HT antagonist) did not modify tizanidine-induced antiallodynia in neuropathic females and males. These data indicate that tizanidine exhibits a sex-dependent antiallodynic effect in neuropathy. Data also suggest that activation of adrenergic α2B and α2A and opioid receptors participate in the antiallodynic effect of tizanidine in female and male, respectively, neuropathic rats.
Assuntos
Neuralgia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Clonidina/análogos & derivados , Clonidina/farmacologia , Clonidina/uso terapêutico , Feminino , Hiperalgesia/tratamento farmacológico , Masculino , Neuralgia/tratamento farmacológico , RatosRESUMO
End-stage kidney disease has a negative impact on patients' quality of life. People who receive a kidney transplant experience an improvement in many areas of their daily life. Sexuality is a general component of health, which can be affected by end-stage kidney disease and kidney transplant. The aim of this study was to explore and understand the experiences and perspectives of kidney transplant recipients regarding their sexuality. A qualitative study based on Gadamer's hermeneutic philosophy was carried out. Two focus groups and nine interviews were conducted with 18 kidney transplant recipients. Data were audio-recorded, transcribed, and analyzed with the help of qualitative analysis software. Two main themes emerged from the data: (1) "The impact of a kidney transplant on sexuality", with the subthemes "sexuality is relegated to the background", "physical decline acts as a sexual inhibitor", and "changes in sexual activity following a kidney transplant"; (2) "Sexual education in kidney transplant recipients" with the subthemes "sexuality: a hidden concern amongst kidney transplant recipients" and "talking about sexuality with healthcare professionals". Sexuality is a frequent concern among kidney transplant recipients. The physiological and emotional changes experienced after kidney transplant exert a great influence on their sexuality. Healthcare professionals rarely discuss sexuality concerns with kidney transplant recipients. Professional sexual education and assistance are necessary to improve sexual health satisfaction of kidney transplant recipients.
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Transient receptor potential ankyrin 1 (TRPA1) channel is expressed in a subset of nociceptive neurons. This channel integrates several nociceptive signals. Particularly, it is modulated by intracellular pH (pHi). Na+/H+ exchanger 1 (NHE1) contributes to the maintenance of pHi in nociceptors. However, it is currently unknown whether the interaction between TRPA1 and NHE1 contributes to the nociceptive processing. Thus, the purpose of this study was to assess the functional interaction between NHE1 and TRPA1 in small dorsal root ganglion (DRG) neurons from primary culture obtained from adult rats. Moreover, we also evaluated their possible interaction in acute and inflammatory pain. Zoniporide (selective NHE1 inhibitor) reduced pHi and increased intracellular calcium in a concentration-dependent fashion in DRG neurons. Zoniporide and allyl isothiocyanate (AITC, TRPA1 agonist) increased calcium transients in the same DRG neuron, whereas that A-967079 (TRPA1 antagonist) prevented the effect of zoniporide in DRG neurons. Repeated AITC induced TRPA1 desensitization and this effect was prevented by zoniporide. Both NHE1 and TRPA1 were localized at the membrane surface of DRG neurons in culture. Local peripheral zoniporide enhanced AITC-induced pronociception and this effect was prevented by A-967079. Likewise, zoniporide potentiated Complete Freund's Adjuvant (CFA)-induced hypersensitivity, effect which was prevented by A-967079 in vivo. CFA paw injection increased TRPA1 and decresed NHE1 protein expression in DRG. These results suggest a functional interaction between NHE1 and TRPA1 in DRG neurons in vitro. Moreover, data suggest that this interaction participates in acute and inflamatory pain conditions in vivo.
Assuntos
Gânglios Espinais , Canais de Potencial de Receptor Transitório , Animais , Neurônios , Nociceptividade , Ratos , Trocador 1 de Sódio-Hidrogênio , Canal de Cátion TRPA1RESUMO
In the articulation between research and health intervention, we see the need to situate comprehensive sexuality education in the triangle formed by the salutogenic approach, the mainstreaming of gender and human rights, and the development of competencies in health promotion. For this purpose, we present a set of investigations carried out in Ecuador and Spain through a qualitative methodology with the respective health interventions that seek to obtain significant results of the teaching-learning process on sexuality. The field work contemplates situations of violence as a health problem, orienting the intervention in health empowerment toward pleasure. The health education experiences implemented allow us to conclude that comprehensive sexuality education reinforces the competencies of health personnel to attend to diversity. These findings, and the results expected in ongoing research, allow us to form a competency framework aimed at specifically improving medical education so that medical professionals can generate health processes with a cross-cutting approach to gender and human rights.
Assuntos
Direitos Humanos , Sexualidade , Equador , Promoção da Saúde , Humanos , EspanhaRESUMO
Extrasynaptic α5 -subunit containing GABAA (α5 -GABAA ) receptors participate in chronic pain. Previously, we reported a sex difference in the action of α5 -GABAA receptors in dysfunctional pain. However, the underlying mechanisms remain unknown. The aim of this study was to examine this sexual dimorphism in neuropathic rodents and the mechanisms involved. Female and male Wistar rats or ICR mice were subjected to nerve injury followed by α5 -GABAA receptor inverse agonist intrathecal administration, L-655,708. The drug produced an antiallodynic effect in nerve-injured female rats and mice, and a lower effect in males. We hypothesized that changes in α5 -GABAA receptor, probably influenced by hormonal and epigenetic status, might underlie this sex difference. Thus, we performed qPCR and western blot. Nerve injury increased α5 -GABAA mRNA and protein in female dorsal root ganglia (DRG) and decreased them in DRG and spinal cord of males. To investigate the hormonal influence over α5 -GABAA receptor actions, we performed nerve injury to ovariectomized rats and reconstituted them with 17ß-estradiol (E2). Ovariectomy abrogated L-655,708 antiallodynic effect and E2 restored it. Ovariectomy decreased α5 -GABAA receptor and estrogen receptor α protein in DRG of neuropathic female rats, while E2 enhanced them. Since DNA methylation might contribute to α5 -GABAA receptor down-regulation in males, we examined CpG island DNA methylation of α5 -GABAA receptor coding gene through pyrosequencing. Nerve injury increased methylation in male, but not female rats. Pharmacological inhibition of DNA methyltransferases increased α5 -GABAA receptor and enabled L-655,708 antinociceptive effect in male rats. These results suggest that α5 -GABAA receptor is a suitable target to treat chronic pain in females.
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Epigênese Genética/genética , Nociceptividade/fisiologia , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/fisiopatologia , Receptores de GABA-A/genética , Receptores de GABA-A/fisiologia , Animais , Metilação de DNA/genética , Estradiol/farmacologia , Feminino , Agonistas GABAérgicos/administração & dosagem , Agonistas GABAérgicos/farmacologia , Gânglios Espinais/metabolismo , Imidazóis/farmacologia , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Medição da Dor , Ratos , Ratos Wistar , Caracteres SexuaisRESUMO
INTRODUCTION: Since the beginning of the COVID-19 pandemic, extensive research has been done on the prognosis of patients with SARS-CoV-2 associated with age, biodemographic conditions, comorbidities, social factors, clinical parameters, inflammatory blood markers, coagulation, biochemical and blood gas parameters, among others. Few studies have addressed this problem in Latin America, so it is of interest to know how the disease plays out in this region. OBJECTIVE: The purpose of our study is to evaluate the course of COVID-19 in patients admitted to a tertiary center in Chile and to assess factors measured close to hospital admission that may be associated with death and the need for invasive mechanical ventilation. METHODS: We did a retrospective cohort study at Indisa Clinic in Santiago, Chile. We included all patients aged 15 years and older hospitalized between March 11 and July 25, 2020. Hospital mortality and severity of the cases were analyzed, and logistic regression models were applied to identify predictors of outcome variables. RESULTS: The sample included 785 subjects. The mean age was 59 years, 59% were men, and 61.3% had comorbidities. Forty five per cent required intensive care, and 24% invasive mechanical ventilation. The overall hospital fatality rate was 18.7%. In intensive care patients, the case fatality was 32.1%, and in those who received invasive mechanical ventilation, it was 59.4%. Independent risk factors for death included age (odds ratio 1.09; 95% confidence interval: 1.07 to 1.12), diabetes (1.68; 1.06 to 2.67), chronic lung disease (2.80; 1.48 to 5.28), increased C-reactive protein, creatinine, and ferritin. No association with sex, public health insurance, history of heart disease, oxygen saturation upon admission, or D-dimer was found. Similar factors were predictors of invasive mechanical ventilation. DISCUSSION: The prognosis and predictive factors in this cohort of patients hospitalized in Chile for COVID-19 were comparable to those reported in similar studies from higher-income countries. Male sex was not associated with a poor prognosis in this group of patients.
INTRODUCCIÓN: Desde el comienzo de la pandemia de COVID-19, se han desarrollado diversas investigaciones sobre el pronóstico de pacientes con SARS-CoV-2 asociado a factores como edad, condiciones biodemográficas, comorbilidades, factores sociales, parámetros clínicos, hematológicos, marcadores inflamatorios, de coagulación, bioquímicos y gasométricos, entre otros. Hasta ahora, existen escasos estudios que hayan abordado el tema en América Latina, por lo que es de interés conocer el comportamiento de la enfermedad en la región. OBJETIVO: Evaluar el curso del COVID-19 en pacientes ingresados en un centro terciario en Chile y analizar factores predictores, medidos en el período cercano a la admisión, que se asocien al pronóstico vital y al uso de ventilación mecánica invasiva. MÉTODOS: Estudio de cohorte retrospectivo realizado en Clínica Indisa de Santiago, Chile. Participaron todos los pacientes de 15 años o más hospitalizados entre el 11 de marzo y el 25 de julio de 2020. Se analizó la letalidad hospitalaria, la complejidad de los casos y se aplicaron modelos de regresión logística para identificar predictores de las variables de resultado definidas. RESULTADOS: La muestra estuvo constituida por 785 sujetos. La edad media fue 59 años, 59% fueron hombres y 61,3% tenía comorbilidades. El 45% requirió cuidados intensivos y 24% ventilación mecánica invasiva. La letalidad hospitalaria global fue de 18,7%. En pacientes de unidad de cuidados intensivos fue 32,1% y en quienes recibieron ventilación mecánica invasiva 59,4%. Los factores de riesgo independientes de morir incluyeron la edad (Odds ratio 1,09; intervalo de confianza 95%: 1,07 a 1,12), diabetes (1,68; 1,06 a 2,67), enfermedad pulmonar crónica (2,80; 1,48 a 5,28) y mayores niveles de proteína C reactiva, creatinina y ferritina. No se demostró asociación con el sexo, pertenencia al seguro público de salud, antecedente de cardiopatía, obesidad, ni dímero D. Similares factores fueron predictores de ventilación mecánica invasiva. CONCLUSIONES: El pronóstico y factores predictores en esta cohorte de pacientes hospitalizados en Chile por COVID-19 fueron comparables en su mayoría a los reportados en estudios similares de países de mayores ingresos. El sexo masculino no fue un factor de mal pronóstico en este grupo de pacientes.
Assuntos
COVID-19/fisiopatologia , Cuidados Críticos/estatística & dados numéricos , Hospitalização , Respiração Artificial/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Chile , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Centros de Atenção Terciária , Adulto JovemRESUMO
Introducción Desde el comienzo de la pandemia de COVID-19, se han desarrollado diversas investigaciones sobre el pronóstico de pacientes con SARS-CoV-2 asociado a factores como edad, condiciones biodemográficas, comorbilidades, factores sociales, parámetros clínicos, hematológicos, marcadores inflamatorios, de coagulación, bioquímicos y gasométricos, entre otros. Hasta ahora, existen escasos estudios que hayan abordado el tema en América Latina, por lo que es de interés conocer el comportamiento de la enfermedad en la región. Objetivo Evaluar el curso del COVID-19 en pacientes ingresados en un centro terciario en Chile y analizar factores predictores, medidos en el período cercano a la admisión, que se asocien al pronóstico vital y al uso de ventilación mecánica invasiva. Métodos Estudio de cohorte retrospectivo realizado en Clínica Indisa de Santiago, Chile. Participaron todos los pacientes de 15 años o más hospitalizados entre el 11 de marzo y el 25 de julio de 2020. Se analizó la letalidad hospitalaria, la complejidad de los casos y se aplicaron modelos de regresión logística para identificar predictores de las variables de resultado definidas. Resultados La muestra estuvo constituida por 785 sujetos. La edad media fue 59 años, 59% fueron hombres y 61,3% tenía comorbilidades. El 45% requirió cuidados intensivos y 24% ventilación mecánica invasiva. La letalidad hospitalaria global fue de 18,7%. En pacientes de unidad de cuidados intensivos fue 32,1% y en quienes recibieron ventilación mecánica invasiva 59,4%. Los factores de riesgo independientes de morir incluyeron la edad (Odds ratio 1,09; intervalo de confianza 95%: 1,07 a 1,12), diabetes (1,68; 1,06 a 2,67), enfermedad pulmonar crónica (2,80; 1,48 a 5,28) y mayores niveles de proteína C reactiva, creatinina y ferritina. No se demostró asociación con el sexo, pertenencia al seguro público de salud, antecedente de cardiopatía, obesidad, ni dímero D. Similares factores fueron predictores de ventilación mecánica invasiva. Conclusiones El pronóstico y factores predictores en esta cohorte de pacientes hospitalizados en Chile por COVID-19 fueron comparables en su mayoría a los reportados en estudios similares de países de mayores ingresos. El sexo masculino no fue un factor de mal pronóstico en este grupo de pacientes.
Introduction Since the beginning of the COVID-19 pandemic, extensive research has been done on the prognosis of patients with SARS-CoV-2 associated with age, biodemographic conditions, comorbidities, social factors, clinical parameters, inflammatory blood markers, coagulation, biochemical and blood gas parameters, among others. Few studies have addressed this problem in Latin America, so it is of interest to know how the disease plays out in this region. Objective The purpose of our study is to evaluate the course of COVID-19 in patients admitted to a tertiary center in Chile and to assess factors measured close to hospital admission that may be associated with death and the need for invasive mechanical ventilation. Methods We did a retrospective cohort study at Indisa Clinic in Santiago, Chile. We included all patients aged 15 years and older hospitalized between March 11 and July 25, 2020. Hospital mortality and severity of the cases were analyzed, and logistic regression models were applied to identify predictors of outcome variables. Results The sample included 785 subjects. The mean age was 59 years, 59% were men, and 61.3% had comorbidities. Forty five per cent required intensive care, and 24% invasive mechanical ventilation. The overall hospital fatality rate was 18.7%. In intensive care patients, the case fatality was 32.1%, and in those who received invasive mechanical ventilation, it was 59.4%. Independent risk factors for death included age (odds ratio 1.09; 95% confidence interval: 1.07 to 1.12), diabetes (1.68; 1.06 to 2.67), chronic lung disease (2.80; 1.48 to 5.28), increased C-reactive protein, creatinine, and ferritin. No association with sex, public health insurance, history of heart disease, oxygen saturation upon admission, or D-dimer was found. Similar factors were predictors of invasive mechanical ventilation. Discussion The prognosis and predictive factors in this cohort of patients hospitalized in Chile for COVID-19 were comparable to those reported in similar studies from higher-income countries. Male sex was not associated with a poor prognosis in this group of patients.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Pneumonia Viral/fisiopatologia , Respiração Artificial/estatística & dados numéricos , Infecções por Coronavirus/fisiopatologia , Cuidados Críticos/estatística & dados numéricos , Hospitalização , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Prognóstico , Chile , Fatores Sexuais , Estudos Retrospectivos , Fatores de Risco , Estudos de Coortes , Mortalidade Hospitalar , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Centros de Atenção TerciáriaRESUMO
El presente estudio fue de tipo observacional comparativo; para lo cual se analizaron 40 cepillos dentales de la marca OralDent, los que fueron usados durante un mes por los integrantes de la Cooperativa de taxis "Simón Bolívar" de la ciudad de Riobamba, Ecuador; con el propósito de comparar la eficacia del ácido acético al 5% y la clorhexidina al 0,12% como desinfectantes. El análisis microbiológico arrojó la presencia de microorganismos en los cepillos dentales usados por los individuos que voluntariamente los cedieron para el estudio, tales como: C. albicans en mayor proporción, seguida de S. viridans, S. epidermidis y S. mutans, A. tubingensis, K. pneumoniae, E. coli, E. faecalis, P. vulgaris. En las muestras con concentraciones de microorganismos de 100.000 UFC/mL, una vez generado el proceso de desinfección con clorhexidina al 0,12% existió una disminución a valores menores de 20.000 UFC/mL o su eliminación completa. El ácido acético al 5% logró una asepsia en el 100% de los cepillos dentales sin importar la edad o el género del individuo que lo utilizó.
The present study was of a comparative observational type. 40 OralDent toothbrushes were analyzed for this reserach, which were used for a month by the members of the "Simón Bolívar" Taxi Cab Company in the city of Riobamba, Ecuador. It aimed to compare the efficacy of 5% acetic acid and 0.12% chlorhexidine as disinfectants. The microbiological analysis showed the presence of microorganisms in the toothbrushes used by the individuals who voluntarily gave them up for the study, for exmaple: C. albicans in a greater proportion, followed by S. viridans, S. epidermidis and S. mutans, A. tubingensis, K. pneumoniae, E. coli, E. faecalis, P. vulgaris. Once the disinfection process with 0.12% chlorhexidine was generated in the samples with microorganism concentrations of 100,000 CFU / mL, there was a decrease to values less than 20,000 CFU / mL or its complete elimination. 5% acetic acid achieved asepsis in 100% of toothbrushes regardless of the age or gender of the individual who used it.
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Humanos , Masculino , Feminino , Clorexidina , Desinfecção , Ácido Acético , Assepsia , Técnicas Microbiológicas , DesinfetantesRESUMO
The role of spinal α5 subunit-containing GABAA (α5-GABAA) receptors in chronic pain is controversial. The purpose of this study was to investigate the participation of spinal α5-GABAA receptors in the reserpine-induced pain model. Reserpine administration induced tactile allodynia and muscle hyperalgesia in female and male rats. Intrathecal injection of L-655,708 and TB 21007 (7 days after the last reserpine injection) decreased tactile allodynia and, at a lesser extent, muscle hyperalgesia in female rats. The effects of these drugs produced a lower antiallodynic and antihyperalgesic effect in male than in female rats. Contrariwise, these drugs produced tactile allodynia and muscle hyperalgesia in naïve rats and these effects were lower in naïve male than female rats. Intrathecal L-838,417 prevented or reversed L-655,708-induced antiallodynia in reserpine-treated female rats. Repeated treatment with α5-GABAA receptor small interfering RNA (siRNA), but not scramble siRNA, reduced reserpine-induced allodynia in female rats. Accordingly, α5-GABAA receptor siRNA induced nociceptive hypersensitivity in naïve female rats. Reserpine enhanced α5-GABAA receptors expression in spinal cord and dorsal root ganglia (DRG), while it increased CD11b (OX-42) and glial fibrillary acidic protein (GFAP) fluorescence intensity in the lumbar spinal cord. In contrast, reserpine diminished K+-Cl- co-transporter 2 (KCC2) protein in the lumbar spinal cord. Data suggest that spinal α5-GABAA receptors play a sex-dependent proallodynic effect in reserpine-treated rats. In contrast, these receptors have a sex-dependent antiallodynic role in naïve rats.
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Fibromialgia/complicações , Dor/complicações , Dor/tratamento farmacológico , Receptores de GABA-A/metabolismo , Reserpina/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Dor/induzido quimicamente , Dor/patologia , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Simportadores/metabolismo , Cotransportadores de K e Cl-RESUMO
Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. However, the role of extrasynaptic α5 subunit-containing GABAA (α5GABAA) receptors in this process is not known. The purpose of this study was to investigate the role of α5GABAA receptors in diabetes-induced tactile allodynia, loss of rate-dependent depression (RDD) of the Hoffmann reflex (HR), and modulation of primary afferent excitability. Intraperitoneal administration of streptozotocin induced tactile allodynia. Intrathecal injection of α5GABAA receptor inverse agonist, L-655,708, produced tactile allodynia in naive rats, whereas it reduced allodynia in diabetic rats. In healthy rats, electrical stimulation of the tibial nerve at 5 Hz induced RDD of the HR, although intrathecal treatment with L-655,708 (15 nmol) abolished RDD of the HR. Streptozotocin induced the loss of RDD of the HR, while intrathecal L-655,708 (15 nmol) restored RDD of the HR. L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4 to L6 dorsal root ganglion. Streptozotocin increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4 to L6 dorsal root ganglia in 10-week diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively, and are tonically active in primary afferents.
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Diabetes Mellitus Experimental/tratamento farmacológico , Agonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Proteínas de Transporte/metabolismo , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/etiologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Ratos Wistar , Reflexo/fisiologia , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal/patologiaRESUMO
Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. However, the function of these transcription factors in pain is unknown. The purpose of this study was to investigate the contribution of ATF2 and ATF3 to nerve injury-induced neuropathic pain. L5/6 spinal nerve ligation induced tactile allodynia and thermal hyperalgesia. Moreover, nerve damage enhanced ATF2 and ATF3 protein expression in injured L5/6 dorsal root ganglia and spinal cord but not in uninjured L4 dorsal root ganglia. Nerve damage also enhanced ATF2 immunoreactivity in dorsal root ganglia and spinal cord 7 to 21 days post-injury. Repeated intrathecal post-treatment with a small-interfering RNA targeted against ATF2 (ATF2 siRNA) or anti-ATF2 antibody partially reversed tactile allodynia and thermal hyperalgesia. In contrast, ATF3 siRNA or anti-ATF3 antibody did not modify nociceptive behaviors. ATF2 immunoreactivity was found in dorsal root ganglia and spinal cord co-labeling with NeuN mainly in non-peptidergic (IB4+) but also in peptidergic (CGRP+) neurons. ATF2 was found mainly in small- and medium-sized neurons. These results suggest that ATF2, but not ATF3, is found in strategic sites related to spinal nociceptive processing and participates in the maintenance of neuropathic pain in rats.
Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Fator 2 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/genética , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Modelos Animais de Doenças , Feminino , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Regulação da Expressão Gênica , Lectinas/metabolismo , Masculino , Microscopia Confocal , Medição da Dor , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/patologia , Fosfopiruvato Hidratase/metabolismo , RNA Interferente Pequeno/administração & dosagem , Ratos , Ratos Wistar , Nervos Espinhais/metabolismo , Nervos Espinhais/patologia , Tato/fisiologiaRESUMO
Propósito: Elaborar una propuesta técnica para mejorar el cumplimiento de los Lineamiento Técnicos de Referencia Retorno e Interconsulta que se implementan en los servicios de salud y fortalecer el trabajo de las redes integrales e integradas. Objetivo: Evaluar el cumplimiento de los Lineamientos Técnicos para la Referencia, Retorno e Interconsulta en la Consulta Externa del Hospital Nacional de Niños "Benjamín Bloom" San salvador, febrero a julio 2018. Materiales y Métodos: Se realizó un estudio descriptivo, transversal y cuantitativo. Resultados: Los Lineamentos Técnicos de Referencia Retorno e Interconsulta son aplicables en forma parcialmente por parte del personal de salud de la Consulta Externa. En los expedientes clínicos no se encontró evidencia escrita por parte de los profesionales. Existen problemas técnicos de abastecimiento de insumos para su cumplimiento. El 85% del personal reconoce la importancia de su aplicación. Conclusiones: Existe conocimiento y cumplimiento parcial de la aplicación de los Lineamientos Técnicos para la Referencia Retorno e Interconsulta por parte del personal de salud de la Consulta Externa del Hospital Nacional de Niños "Benjamín Bloom". Recomendaciones: Desarrollar un programa educativo dirigido al personal sobre la aplicación de los Lineamentos Técnicos de Referencia Retorno e Interconsulta y monitorear su cumplimiento. Dar seguimiento al sistema que ya tienen los otros hospitales en el ministerio de salud
Assuntos
Encaminhamento e Consulta , Administração HospitalarRESUMO
Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED50 = 2.79 ± 0.16 mg/kg) or gabapentin (ED50 = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED50 = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (â¼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Aminas/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Hiperalgesia/tratamento farmacológico , Naltrexona/administração & dosagem , Neuralgia/tratamento farmacológico , Pregabalina/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Administração Oral , Aminas/uso terapêutico , Animais , Ácidos Cicloexanocarboxílicos/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Gabapentina , Humanos , Injeções Espinhais , Naltrexona/uso terapêutico , Neuralgia/etiologia , Limiar da Dor/efeitos dos fármacos , Pregabalina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
The purpose of this study was to investigate whether 1%, 2% or 5% formalin injection produce hypersensitivity with characteristics of the neuropathic pain induced by spinal nerve injury. Formalin injection (1%, 2% and 5%) produced concentration-dependent long-lasting (at least 14 days) mechanical allodynia and hyperalgesia in both paws. Likewise, L5/L6 spinal nerve ligation induced allodynia and hyperalgesia in both paws. The intensity of hypersensitivity was greater in the ipsilateral than in the contralateral paw in all models. Systemic gabapentin or morphine completely reduced 1% formalin-induced hypersensitivity. In contrast, both drugs were not able to fully diminish 2-5% formalin- and nerve injury-induced hypersensitivity. Indomethacin produced a significant effect in the chronic 1% formalin test. Conversely, this drug did not modify 2 or 5% formalin- and nerve injury-induced hypersensitivity. Spinal nerve injury and 2-5%, but not 1%, formalin injection enhanced ATF3 protein expression and immunofluorescence in dorsal root ganglia (DRG) in a time-dependent manner. Furthermore, 2-5%, but not 1%, formalin injection or spinal nerve injury also enhanced α2δ-1 subunit protein levels in DRG. Our results suggest that 5% and, at lesser extent, 2% formalin injection produces long-lasting hypersensitivity with a pharmacological and molecular pattern that resembles neuropathic pain induced by spinal nerve ligation.
Assuntos
Formaldeído/farmacologia , Neuralgia/induzido quimicamente , Fator 3 Ativador da Transcrição/metabolismo , Aminas/farmacologia , Animais , Ácidos Cicloexanocarboxílicos/farmacologia , Feminino , Formaldeído/administração & dosagem , Gabapentina , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Indometacina/farmacologia , Injeções , Ligadura/efeitos adversos , Morfina/farmacologia , Neuralgia/metabolismo , Ratos , Fatores de Tempo , Ácido gama-Aminobutírico/farmacologiaRESUMO
Serotonin (5-HT) participates in pain modulation by interacting with different 5-HT receptors. The role of 5-HT5A receptor in neuropathic pain has not previously studied. The purpose of this study was to investigate: A) the role of 5-HT5A receptors in rats subjected to spinal nerve injury; B) the expression of 5-HT5A receptors in dorsal spinal cord and dorsal root ganglia (DRG). Neuropathic pain was induced by L5/L6 spinal nerve ligation. Tactile allodynia in neuropathic rats was assessed with von Frey filaments. Western blot methodology was used to determine 5-HT5A receptor protein expression. Intrathecal administration (on day 14th) of 5-HT (10-100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03-0.3 nmol) reversed nerve injury-induced tactile allodynia. Intrathecal non-selective (methiothepin, 0.1-0.8 nmol) and selective (SB-699551, 1-10 nmol) 5-HT5A receptor antagonists reduced, by ~60% and ~25%, respectively, the antiallodynic effect of 5-HT (100 nmol) or 5-CT (0.3 nmol). Moreover, both selective 5-HT1A and 5-HT1B/1D receptor antagonists, WAY-100635 (0.3-1 nmol) and GR-127935 (0.3-1 nmol), respectively, partially diminished the antiallodynic effect of 5-HT or 5-CT by about 30%. Injection of antagonists, by themselves, did not affect allodynia. 5-HT5A receptors were expressed in the ipsilateral dorsal lumbar spinal cord and DRG and L5/L6 spinal nerve ligation did not modify 5-HT5A receptor protein expression in those sites. Results suggest that 5-HT5A receptors reduce pain processing in the spinal cord and that 5-HT and 5-CT reduce neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors. These receptors could be an important part of the descending pain inhibitory system.
Assuntos
Neuralgia/metabolismo , Receptores 5-HT1 de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Medula Espinal/metabolismo , Nervos Espinhais/lesões , Analgésicos/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Vértebras Lombares , Metiotepina/farmacologia , Neuralgia/tratamento farmacológico , Oxidiazóis/farmacologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos Wistar , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT1B de Serotonina/metabolismo , Receptor 5-HT1D de Serotonina/metabolismo , Serotonina/análogos & derivados , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Medula Espinal/efeitos dos fármacos , TatoRESUMO
Ursolic acid (1) and a new flavanone, 5-O-(6-rhamnosylglucoside)-7-hydroxy-4'-methoxyflavanone (2), were isolated from the leaves of Salvia elegans Vahl. These natural products displayed antidepressant activity in mice as determined by means of a forced swimming test (FST) evaluation. Structural elucidation was carried out by chemical derivatization (acetylation) and spectroscopic analyses, such as 1H- and 13C-NMR and two-dimensional (2-D) COSY, heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple-bond correlation (HMBC) spectroscopy experiments.
Assuntos
Antidepressivos/química , Antidepressivos/uso terapêutico , Flavanonas/química , Flavonoides/química , Salvia/química , Animais , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Neste trabalho realizou-se um estudo histológico de sete coroas obtidas de dentes portadores de tratamento endodôntico com diferentes tipos de pigmentaçöes intrínsecas, com mais de 10 anos, causadas por hemorragia, necrose pulpar e medicamentos bem como de uma coroa dentária sem pigmentaçäo (controle) nos quais foram realizados cortes por desgaste e observados com auxílio de microscopia óptica. Os achados evidenciaram que os pigmentos concentravam-se näo somente no interior dos canalículos dentinários como também na substância internalicular e nas zonas interglobulares e, em todos os casos, constatou-se a presença de formas cocáceas no interior dos canalículos dentinários