Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Biochemical and histopathological evaluations of chronic renal failure rats treated with pluripotent human stem cells

Abstract Regeneration of damaged kidney cells using stem cells is the current research approach in the treatment of chronic renal failure (CRF). In the present study, the histopathological and biochemical techniques were used to evaluate stem cells' (SCs) role in treatment of CRF. Sixty-four rats were divided into eight groups. Group I (GI): rats were injected with doxorubicin (15 mg/kg) to initiate CRF. GII-GVII: rats were injected with doxorubicin and treated with SCs (1x106 MSCs or/and 2x104 HSCs/rat) with/without growth factors extract (200 µL/rat) and/or immunosuppressor (cyclosporine A, 5 mg/kg/day). GVIII: rats treated with PBS (100 µL/kg/day). Levels of creatinine, urea and uric acid were increased in rats sera after injection with doxorubicin, while blood electrolyte levels of Na, K, P and Mg were decreased. Also, histopathological abnormalities such as hyalinized blood vessels, degenerated hyalinized glomerulus tubules and cell debris in the lumen and degeneration of renal tissues were observed in these rats. After treatment with SCs, all these parameters restore their normal values with regeneration of the damaged cells as demonstrated in histopathology of the treated groups. It can be concluded that, the use of SCs in treatment of kidney diseases is a promising approach and needs more efforts.

Small bronchiolar histopathological changes related to prolonged diabetes / Pequeños cambios histopatológicos bronquiolares relacionados con la diabetes prolongada

SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.

RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.

Vitamin C administration attenuated artemether induced hepatic injury in rats / La aAdministración de vitamina C atenúa la lesión hepática inducida por artemeter en ratas

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.

Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.

The Effect of Tadalafil on Renal Fibrosis Induced by Ureteral Obstruction / Efecto del Tadalafil en la Fibrosis Renal Inducida por Obstrucción Uretral

ABSTRACT Objective: It has been reported that phosphodiesterase-5 (PDE-5) inhibitors improve kidney function during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE-5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n = 6) as sham-operated, UUO and tadalafil-treated (10 mg/72 hours, ig) UUO (UUO+T) groups. Unilateral ureteral obstruction was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cyclic guanosine monophosphate (cGMP), renal alpha-smooth muscle actin (α-sma) and transforming growth factor βeta (TGF-β) levels, as well as histologic changes, were observed in all the animals. Results: Unilateral ureteral obstruction-induced renal fibrosis was confirmed by increased α-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored the animals 'urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in their kidneys. Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.

RESUMEN Objetivo: Se ha reportado que los inhibidores de la fosfodiesterasa-5 (PDE-5) mejoran las funciones renales durante la insuficiencia renal aguda y crónica. Este estudio tuvo por objetivo determinar los posibles efectos terapéuticos del tadalafil - un inhibidor específico de la PDE-5 - sobre la fibrosis renal inducida por una obstrucción ureteral unilateral (OUU). Métodos: Se utilizaron ratas machos Sprague-Dawley, divididas de manera aleatoria en tres grupos (n = 6): operación simulada, OUU y tratamiento con tadalafil (10 mg/72 horas, IG), y OUU (OUU+T). La obstrucción uretral unilateral fue inducida por una ligadura completa del uréter izquierdo y 14 días después de la cirugía, se observaron niveles de monofosfato de guanosina cíclico (GMP) urinario, alfa-actina de músculo liso (α-SMA), y factor de crecimiento transformante βeta (FCT-β), así como cambios histológicos en todos los animales. Resultados: La fibrosis renal inducida por obstrucción uretral unilateral fue confirmada por un aumento del nivel de α-SMA, deposición de colágeno, dilatación tubular, infiltración de células inflamatorias y necrosis. También se observó un aumento del nivel de FCT-β renal y una disminución del nivel de GMP urinario en los animales con obstrucción, además de una reducción del aclaramiento de la creatinina. El tratamiento con tadalafil, que restauró el nivel de GMP urinario de los animales, atenuó significativamente los cambios fibróticos y el aumento de FCT-β en los riñones. Conclusión: Este estudio sugiere que el tratamiento con tadalafil mejora la fibrosis renal al reducir la expresión de FCT-β y puede tener una importante relevancia clínica por cuanto el tadalafil se usa hoy día clínicamente para tratar la disfunción eréctil y la hipertensión pulmonar.

Salvianolic acid A alleviates the renal damage in rats with chronic renal failure

Abstract Purpose: To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF). Methods: The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined. Results: After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05). Conclusion: SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.

Involvement of adenosine A1 receptor in electroacupuncture-mediated inhibition of astrocyte activation during neuropathic pain / Envolvimento do receptor de adenosina A1 na inibição da ativação de astrócitos mediada por eletroacupuntura durante a dor neuropática

ABSTRACT Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the central or peripheral nervous system. Electroacupuncture (EA) has an antinociceptive effect on neuropathic pain, which is partially due to inhibiting astrocyte activation in the spinal cord. We found that an intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, reversed the antinociceptive effects of EA in a chronic constriction injury-induced neuropathic pain model. The expression of GFAP in L4-L6 spinal cord was significantly upgraded, while DPCPX suppressed the effect of the EA-mediating inhibition of astrocyte activation, as well as wiping out the EA-induced suppression of cytokine content (TNF-α). These results indicated that the adenosine A1 receptor is involved in EA actions during neuropathic pain through suppressing astrocyte activation as well as TNF-α upregulation of EA, giving enlightenment to the mechanisms of acupuncture analgesia and development of therapeutic targets for neuropathic pain.

RESUMO A dor neuropática é uma condição de dor crônica causada por dano ou disfunção do sistema nervoso central ou periférico. A eletroacupuntura (EA) tem um efeito antinociceptivo durante a dor neuropática, que é parcialmente devido à inibição da ativação de astrócitos na medula espinhal. Descobrimos que a injeção intratecal de 8-ciclopentil-1,3-dipropilxantina (DPCPX), um antagonista seletivo do receptor de adenosina A1, reverteu os efeitos antinociceptivos da EA no modelo de dor neuropática induzida por lesão por constrição crônica (CCI). A expressão da GFAP na medula espinal L4-L6 foi significativamente melhorada, enquanto a DPCPX suprimiu o efeito da inibição mediadora da EA na ativação de astrócitos, bem como eliminou a supressão induzida pela EA do conteúdo de citocina (TNF-α). Esses resultados indicam que o receptor de adenosina A1 está envolvido nas ações da EA durante a dor neuropática, suprimindo a ativação astrocitária, bem como o aumento da TNF-α na EA, fornecendo esclarecimentos sobre os mecanismos de analgesia da acupuntura e o desenvolvimento de alvos terapêuticos para dor neuropática.

Moderate intensity physical exercise: psychoneuroimmunological aspects / Exercício físico de intensidade moderada: aspectos psiconeuroimunológicos / Ejercicio físico de intensidad moderada: aspectos psiconeuroinmunológicos

The literature presents several instances of interaction between the nervous system (NS) and the immune system (IS). These interactions are promoted by several molecules, such as cytokines and hormones, with modulating action for both the NS and IS. In this sense, the two systems may influence each other: changes in behavior may be accompanied by alterations in the IS (e.g., immunosuppression) and immunological disorders, such as infections, may modulate behavior (e.g., anxiety and depression). Considering that chronic stress, in addition to affecting behavior, also modulates the IS and that there is evidence that moderate intensity physical exercise (PE) protects physical and mental health, the objective of this review is to explore the influence of moderate-intensity PE on behavior and immunity. Level of Evidence V; Expert opinion.

A literatura apresenta diversas instâncias de interação entre o sistema nervoso (SN) e o sistema imunológico (SI). Essas interações são promovidas por diversas moléculas, como citocinas e hormônios com ação moduladora tanto para o SN quanto o SI. Nesse sentido, os dois sistemas podem ter influência mútua: as alterações do comportamento podem ser acompanhadas por alterações do SI (por exemplo, imunossupressão), e distúrbios imunológicos como infecções, podem modular o comportamento (por exemplo, ansiedade e depressão). Considerando que o estresse crônico, além de afetar o comportamento, modula o SI e que há evidências de que o exercício físico (EF) de intensidade moderada ajuda a proteger a saúde física e mental, o objetivo da presente revisão é explorar a influência do EF de intensidade moderada sobre o comportamento e a imunidade. Nível de Evidência V; Opinião do especialista.

La literatura presenta diversas instancias de interacción entre el sistema nervioso (SN) y el sistema inmune (SI). Estas interacciones son promovidas por diversas moléculas, como citosinas y hormonas, con acción moduladora tanto para el SN como para el SI. En este sentido, los dos sistemas pueden influenciarse mutuamente: los cambios en el comportamiento pueden ser acompañados por alteraciones en el SI (inmunosupresión) y los disturbios inmunológicos, como infecciones, pueden modular el comportamiento (ej. ansiedad y depresión). Considerando que el estrés crónico, además de impactar el comportamiento, también modula el SI y que hay evidencias de que el ejercicio físico (EF) de intensidad moderada es un protector para la salud física y mental, el objetivo de la presente revisión es explotar la influencia del EF de intensidad moderada en el comportamiento y la inmunidad. Nivel de Evidencia V; Opinión del especialista.

Immunohistopathological and Biochemical Study of the Effects of Dead Nettle (Urtica Dioica) Extract on Preventing Liver Lesions Induced by Experimental Aflatoxicosis in Rats / Estudio inmunohistopatológico y bioquímico de los efectos del extracto de la ortiga mayor (Urtica dioica) en la prevención de lesiones hepáticas inducidas por aflatoxicosis experimental en ratas

ABSTRACT Objective: Aflatoxicosis is a mycotoxicosis infection with an acute or chronic course that forms due to aflatoxins (AFs) in humans and animals. Aflatoxins primarily affect the liver and can lead to histopathological necrosis, fibrosis and hepatocarcinogenesis of the organ. This paper studied the preventive effects of dead nettle leaf (Urtica dioica leaf; UDL) extract on liver lesions that were induced by experimental aflatoxicosis in rats. Methods: A total of 30 rats were separated into three groups of 10 rats each. Experimental group A (control) received normal rat food, experimental group B (AFB1) received 2 mg/kg of AF, and experimental group C (AFB1 + UDL extract) received 2 mg/kg of AF + 2 ml/rat/day of UDL extract. After three months of experimentation, blood and tissue samples were taken from the rats by necropsy to perform chemical and histopathological analyses. Results: According to the biochemical and histopathological findings, antioxidant system activity increased and lipid peroxidation and liver enzyme levels decreased in the group that received UDL extract. Conclusion: The extract of UDL had hepatoprotective effects against aflatoxicosis.

RESUMEN Objetivo: La aflatoxicosis es una infección por micotoxicosis con un curso agudo o crónico producido por aflatoxinas (AF) en seres humanos y animales. Las aflatoxinas afectan principalmente el hígado y pueden conducir a necrosis histopatológica, fibrosis o hepatocarcinogénesis del órgano. En este trabajo se estudiaron los efectos preventivos del extracto de la hoja de ortiga mayor (Urtica dioica l; UDL) sobre las lesiones hepáticas inducidas por aflatoxicosis experimental en ratas. Métodos: Un total de 30 ratas se separaron en tres grupos de 10 ratas cada una. EL grupo experimental A (control) recibió comida normal de ratas; el grupo experimental B (AFB1) recibió 2 mg/kg de AF; y el grupo experimental C (AFB1 + extracto de UDL) recibió 2 mg/kg de AF + 2 ml/rata/día de extracto de UDL. Después de tres meses de experimentación, se tomaron muestras de sangre y tejidos de las ratas en una necropsia encaminada a realizar análisis químicos e histopatológicos. Resultados: Según los hallazgos bioquímicos e histopatológicos, la actividad del sistema antioxidante aumentó, y la peroxidación del lípido y los niveles de la enzima del hígado disminuyeron en el grupo que recibió el extracto de UDL. Conclusión: El extracto de UDL tuvo efectos hepatoprotectores contra la aflatoxicosis.

Determinantes da autoavaliação de saúde no Brasil e a influência dos comportamentos saudáveis: resultados da Pesquisa Nacional de Saúde, 2013 / Determinants of self-rated health and the influence of healthy behaviors: results from the National Health Survey, 2013

RESUMO: Objetivo: Investigar os determinantes da autoavaliação de saúde (AAS) no Brasil e a influência dos comportamentos saudáveis. Métodos: Foram usados os dados da Pesquisa Nacional de Saúde (PNS) de 2013. A AAS foi categorizada em muito boa/boa, regular, ruim/muito ruim. Foram testadas diferenças na distribuição da AAS segundo faixa de idade e sexo e foram usados modelos de regressão logística para investigar os efeitos de grau de escolaridade, raça/cor e presença de pelo menos uma doença crônica não transmissível (DCNT) sobre a AAS ruim/muito ruim. Adicionalmente, testou-se a influência dos comportamentos saudáveis, controlando-se os efeitos dos fatores sociodemográficos e presença de pelo menos uma DCNT. Resultados: Foram analisados 60.202 indivíduos, 66,1% avaliaram o seu estado de saúde como muito bom/bom, e 5,9%, como ruim/muito ruim; 47,1% referiram o diagnóstico de pelo menos uma DCNT; e apenas 9,3% disseram ter "estilo de vida saudável" (não usa produtos de tabaco, consome frutas e hortaliças e pratica atividade física no lazer). Entre os fatores sociodemográficos, idade, sexo, grau de escolaridade e raça mostraram associações significativas com a AAS, bem como a presença de pelo menos uma DCNT. Os efeitos de todos os comportamentos saudáveis foram significativos, mesmo após o controle dos demais determinantes. Conclusão: Embora a adoção dos comportamentos saudáveis no Brasil ainda seja insuficiente, a associação dos hábitos saudáveis com a percepção da saúde encontrada neste estudo é um indício de que a população brasileira já começa a relacionar os comportamentos saudáveis ao seu bem-estar e à avaliação melhor da saúde.

ABSTRACT: Objective: To investigate the determinants of self-rated health in Brazil and the influence of healthy lifestyles. Methods: We used data from the National Health Survey (PNS), 2013. The self-rated health was categorized as very good/good, fair, and poor/very poor. Differences in the distribution of self-rated health according to the age group and sex were tested. Logistic regression models were used to test the effects of educational level, race/skin color, and the presence of at least one noncommunicable chronic disease on poor/very poor health perception. In addition, the influence of healthy behaviors was tested controlling for the effects of sociodemographic factors and the presence of at least one chronic disease. Results: We analyzed 60,202 individuals; about 66.1% rated their health as very good/good and 5.9% as poor/very poor; about 47.1% reported the diagnosis of at least one noncommunicable chronic disease; and only 9.3% reported a "healthy lifestyle" (do not use tobacco products, consume fruits and vegetables properly, and do physical activity during leisure time). Among the sociodemographic factors, age, sex, educational level, and race were significantly associated with self-rated health and the presence of at least one chronic disease. The effects of all healthy behaviors were statistically significant even after controlling for the other determinants. Conclusion: Although the adoption of healthy lifestyles in Brazil is still insufficient, the association of healthy practices with self-perception of health found in this study is an indication that the Brazilian population is beginning to relate healthy behaviors to their well-being and better health evaluation.

Idosos vítimas de trauma: doenças preexistentes, medicamentos em uso no domicílio e índices de trauma / Elderly victims of trauma: preexisting conditions, medications taken at home and indexes of trauma / Ancianos víctimas de trauma: condiciones preexistentes, medicamentos tomados en el hogar e índices de trauma

Objetivou-se identificar o perfil sociodemográfico de idosos vítimas de trauma, caracterizar doenças preexistentes e medicamentos utilizados no domicílio; calcular índices de trauma e desfecho clínico. Estudo retrospectivo e exploratório, com a análise de dados secundários de um banco de dados de um hospital geral terciário, entre 2008 e 2010. Foram estudados 131 idosos, média de idade 69,9 anos, 73,3% homens, 55,1% casados, 54,7% aposentados; 65,6% possuíam doenças preexistentes e 48,9% usavam medicamentos no domicílio. Houve representatividade de quedas (31,3%), seguidas por atropelamento (28,2%), com cabeça/pescoço sendo a região mais acometida (59,5%). Prevaleceu o trauma moderado (44,3%), com condições de sobrevida após o evento (80,2%). Houve associação entre mecanismo do trauma e doença preexistente (p=0,01) e entre mecanismo do trauma e sexo (p=0,03). O conhecimento das variáveis envolvidas com idosos vítimas de trauma possibilita aos profissionais de saúde o planejamento de medidas preventivas, visando aprimorar sua assistência.

The objective was to identify the sociodemographic profile of the elderly victims of trauma, to characterize preexisting conditions and medications taken at home, and to calculate indices of trauma and clinical outcomes. This is a retrospective and exploratory analysis from a database of a general hospital between 2008 and 2010. There were studied 131 elderly, mean age 69.9 years, 73.3% male, 55.1% married, 54.7% retired, 65.6% had preexisting conditions and 48.9% used drugs at home. There was a representative number of falls (31.3%), followed by running over (28.2%), with the head/neck region being the most affected (59.5%). Moderate trauma prevailed (44.3%), with conditions of survival after the event (80.2%). There was an association between mechanism of trauma and preexisting disease (p=0.01) and between mechanism of trauma and sex (p=0.03). The knowledge of the variables involved with the elderly victims of trauma enables healthcare professionals to plan preventive measures aimed at improving the assistance. Key words: Aged; Wounds and Injuries; Disease; Drug Utilization.

Se objetivó identificar el perfil sociodemográfico de ancianos víctimas de trauma, caracterizar condiciones preexistentes y medicamentos tomados en casa, y calcular índices de trauma y evolución clínica. Se realizó un análisis retrospectivo y exploratorio de una base de datos de un hospital general terciario entre 2008 y 2010. Se estudiaron 131 ancianos, media of 69,9 años, 73,3% hombres, 55,1% casados, 54,7% jubilados, 65,6% tienen condiciones preexistentes y 48,9% estaban tomando medicación en casa. Hubo representación de las caídas (31,3%), seguido de atropello (28,2%). La región cabeza/cuello fue el más afectado (59,5%). Prevaleció trauma moderado (44,3%), con condiciones de supervivencia después del evento (80,2%). Se observó una asociación entre mecanismo de lo trauma y enfermedad previa (p=0,01) y entre mecanismo de lo trauma y sexo (p=0,03). El conocimiento de las variables que intervienen con ancianos víctimas de trauma permite a los profesionales de la salud planificar medidas preventivas para mejorar su asistencia.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Efectos de las experiencias adversas temprana y tardía en las características morfométricas y estereológicas de la glándula suprarrenal de ratas Sprague Dawley sometidas a estrés durante su vida adulta / Effects of early and late adverse experiences in morphometric and stereological characteristics of the adrenal gland of Sprague Dawley rats subjected to stress during adulthood

La ruptura temprana del vínculo materno y el aislamiento social son variables que están involucradas con los comportamientos social y emocional y también con el aumento de la ansiedad, especialmente en situaciones estresantes. Sin embargo, no se dispone de investigaciones que expliquen los cambios morfológicos de la glándula suprarrenal (GSR). Por lo anterior, el objetivo de este trabajo fue conocer experimentalmente, a través del modelo de alteración del vínculo social temprano madre-cría y alteración del vínculo social tardío por aislamiento, el efecto sobre las características morfométricas y estereológicas de la GSR, en ratas de la cepa Sprague Dawley sometidas a estrés crónico intermitente en la vida adulta. Utilizamos 35 ratas hembras recién nacidas, distribuidas en grupos de 7, en condiciones de lactancia y alimentación estandarizadas. Los grupos experimentales fueron expuestos a experiencias adversas temprana (E1), tardía (E2), temprana-tardía (E3) y posteriormente, sometidas a estrés crónico intermitente en la adultez. Se aisló la GSR izquierda de cada animal determinando características morfométricas y parámetros estereológicos. El peso absoluto fue mayor en los grupos control C2 y grupo experimental (E1). El número de células por mm3, el porcentaje de tejido glandular y la densidad de superficie en la zona fascicular de la GSR fue menor en el grupo E3. Las características estereológicas de la GRS en ratas, no sólo pueden ser afectadas por la exposición al estrés en la adultez, sino que también las experiencias adversas temprana y/o tardía juegan un rol importante en los cambios de los parámetros morfológicos cuantitativos observados en esta glándula.

The early break in maternal bonding and social isolation are variables involved with social and emotional behaviors and also with increased anxiety, especially in stressful situations. However, there is no research to explain the morphological changes of the adrenal gland (GSR). Therefore, our objective was to experimentally study through alteration model of social ties and early mother-cub bond alteration belated social isolation, the effect on the morphometric and stereological characteristics of the GSR in rats of the Sprague Dawley subjected to intermittent chronic stress in adulthood. We used 35 newborn female rats, divided into groups of 7 under lactating and standardized feeding conditions. The experimental groups were exposed to adverse experiences early (E1), late (E2), and early/late (E3) and subsequently, subject to intermittent chronic stress in adulthood. Left GSR was isolated from each animal determining morphometric characteristics and stereological parameters. The absolute weight was higher in control group C2 and the experimental group E1. In the group E3 number of cells per mm3, the percentage of glandular tissue and density of the surface in the fascicular area of the GSR was lower. Stereological characteristics of the GRS in rats, not only can be affected by exposure to stress in adulthood, but also early and / or late adverse experiences play an important role in the changes of quantitative morphological parameters observed in this gland.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Consideraciones para la transformación del sistema de salud del Ecuador desde una perspectiva de equidad / Equity-based considerations for transforming the Ecuadorian health system

Objectivo El propósito del presente estudio es analizar las inequidades socioeconómicas en la utilización de servicios de salud en el Ecuador, las inequidades en la distribución geográfica de recursos humanos en salud, y reflexionar sobre los retos de equidad que el sistema de salud ecuatoriano enfrenta en la actualidad. Métodos Se utilizó la Encuesta Demográfica y de Salud Materno-Infantil (ENDEMAIN 2004) como la principal fuente de datos, cuya muestra es representativa de la población ecuatoriana. Para estimar los efectos en utilización de servicios de salud utilizamos análisis multivariado multinivel (usando el paquete estadístico MLWiN 2.02) y análisis espacial de recursos en salud (usando GeoDa 1.0.1 ). Resultados Nuestro análisis encontró que inequidades sociales, económicas y geográficas limitan el acceso a servicios de salud en el Ecuador. Hogares de bajos recursos, indígenas y aquellos que viven enáreas rurales (muchos con las tres características a la vez) tienen menos posibilidades de utilizar servicios de salud. A pesar de la marcada concentración de proveedores de salud en zonas urbanas, encontramos que la presencia de personal de salud (excluyendo a médicos) en entidades públicas rurales incrementa la posibilidad de utilización de servicios preventivos y curativos. Conclusiones Los esfuerzos para transformar el sistema de salud deben reducir barreras sociales, culturales, financieras; y las desigualdades en la distribución de recursos humanos en salud, particularmente en elárea rural. Consideramos que la orientación comunitaria y familiar de los servicios, y el incremento de espacios de participación ciudadana son necesarios para reducir dichas inequidades.

Objective The present study was aimed at analysing socioeconomic inequity regarding the use of health services in Ecuador, inequity regarding the geographic distribution of healthcare-related human resources and reflecting on the challenges concerning equity which the Ecuadorian health system is currently facing. Methods The Ecuadorian Demographic, Maternal and Infant Health Survey (2004) was used as the main data source, as its sample was representative of the Ecuadorian population. Multilevel multivariate analysis (MLWiN 2.02 statistical software) and spatial data analysis regarding health resources (GeoDa 1.0.1) were used for estimating the effects of using health services. Results It was found that social, economic and geographic inequity limited access to health services in Ecuador. People living in low economic resource households or indigenous housing and people living in rural areas (many of them having all three characteristics at the same time) had less possibility of using health services. In spite of a marked concentration of health-service providers in urban areas, it was found that the presence of healthcare personnel (excluding doctors) in rural public entities increased the possibility of using preventative and curative services. Conclusions Efforts at transforming the Ecuadorian health system must be aimed at reducing social, cultural and financial barriers and inequality regarding the distribution de healthcare-related human resources, particularly in rural areas. Community and family orientation of the services and increasing spaces for citizen participation are necessary for reducing such inequity.

Nefropatia crônica por ciclosporina: papel do ácido úrico e do sistema renina angiostensina aldosterona como mediadores de disfunção endotelial, inflamação e vasculopatia / Cyclosporine nephropathy: effect of uric acid and the renin angiostensin aldosterone system as mediators of endothelial dysfunction, inflammation and vasculopathy

A nefrotoxicidade por ciclosporina caracteriza-se, do ponto de vista histológico, por fibrose intersticial em faixa, atrofia tubular e hialinose de arteríolas aferentes glomerulares, ou seja, um quadro compatível com doença renal isquêmica. Esta isquemia provocada pela ciclosporina leva a redução da taxa de filtração glomerular, com consequente elevação dos níveis séricos de ácido úrico. Além disto, a ciclosporina altera o transporte tubular de urato, favorecendo o desenvolvimento de hiperuricemia. No modelo experimental de nefropatia pela ciclosporina, a elevação dos níveis de ácido úrico apresenta associação com lesão túbulo intersticial mais severa, além de maior frequência de hialinose de arteríola aferente. Em estudos anteriores demonstramos que a hiperuricemia agrava a nefrotoxicidade pela ciclosporina e também que, a administração concomitante de agentes hipouricemiantes previne a lesão renal pela CsA. Assim, consideramos a hipótese de que, em um modelo experimental de nefropatia crônica pela ciclosporina, instalada, a normalização dos níveis de ácido úrico com alopurinol ou benzbromarona poderia reverter a lesão renal estabelecida. Nefropatia pela ciclosporina foi induzida em ratos Sprague Dawley com injeções subcutâneas diárias de ciclosporina, em associação com dieta hipossódica, por 5 semanas. Ao final deste período, grupos experimentais foram divididos com interrupção da ciclosporina, tratamento com CsA isolada ou em associação com alopurinol ou benzbromarona por um período adicional de 4 semanas. Ao final de 9 semanas de estudo, foram realizadas avaliações funcionais e histológicas...

Chronic allograft nephropathy is characterized by stripped tubular atrophy and interstitial fibrosis, in presence of arteriolar hyalinosis, resembling an ischemic pattern of chronic kidney disease. Chronic ischemia is associated with reduced glomerular filtration rate, and increase in serum uric acid levels. Cyclosporine per se also has a direct effect on tubular urate handling that facilitates the development of hyperuricemia. Hyperuricemia exacerbates chronic cyclosporine nephropathy, with a more severe tubulointerstitial fibrosis and atrophy, as well as worsening of arteriolar hyalinosis. In a previous study we have shown that concomitant treatment with uric acid lowering agents limits the development of experimental CsA nephropathy. The hypothesis of the present study was that treatment with uric acid lowering agents, after the development of CsA nephropathy could reverse or reduce the severity of tubulointerstitial disease. Male Sprague Dawley rats received daily SC injections of cyclosporine in presence of low salt diet, during 5 weeks. At the end of this period, experimental groups were assigned for CsA withdrawal, maintenance of daily CsA alone or associated with allopurinol or benzbromarone in drinking water for an additional period of 4 weeks. At the end of 9 weeks of study, rats were sacrificed for functional and morphological analysis of kidneys...

Epidermal growth factor receptors, testosterone levels and parotid gland changes in rats infected with Trypanosoma cruzi

It has been demonstrated that parotid glands of rats infected with Trypanosoma cruzi present severe histological alterations; changes include reduction in density and volume of the acini and duct systems and an increase in connective tissue. We evaluated the association between morphological changes in parotid glands, circulating testosterone levels and epidermal growth factor receptor (EGF-R) expression in experimental Chagas disease in rats. Animals at 18 days of infection (acute phase) showed a significant decrease in body weight, serum testosterone levels and EGF-R expression in the parotid gland compared with a control group. Since decreases in body weight could lead to a reduction in circulating testosterone concentration, we believe that the reduction in EGF-R expression in parotid glands of infected rats is due to alterations in testosterone levels and atrophy of parotid glands is caused by changes in EGF-R expression. Additionally, at 50 days (chronic phase) of infection parotid glands showed a normal histological aspect likely due to the normalization of the body weight. These findings suggest that the testosterone-EGF-R axis is involved in the histological changes.

Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro

The pathogenesis of chagasic cardiomyopathy is not completely understood, but it has been correlated with parasympathetic denervation (neurogenic theory) and inflammatory activity (immunogenic theory) that could affect heart muscarinic acetylcholine receptor (mAChR) expression. In order to further understand whether neurogenic and/or immunogenic alterations are related to changes in mAChR expression, we studied two models of Trypanosoma cruzi infection: 1) in 3-week-old male Sprague Dawley rats chronically infected with T. cruzi and 2) isolated primary cardiomyocytes co-cultured with T. cruzi and peripheral blood mononuclear cells (PBMC). Using [³H]-quinuclidinylbenzilate ([³H]-QNB) binding assays, we evaluated mAChR expression in homogenates from selected cardiac regions, PBMC, and cultured cardiomyocytes. We also determined in vitro protein expression and pro-inflammatory cytokine expression in serum and cell culture medium by ELISA. Our results showed that: 1) mAChR were significantly (P < 0.05) up-regulated in right ventricular myocardium (means ± SEM; control: 58.69 ± 5.54, N = 29; Chagas: 72.29 ± 5.79 fmol/mg, N = 34) and PBMC (control: 12.88 ± 2.45, N = 18; Chagas: 20.22 ± 1.82 fmol/mg, N = 19), as well as in cardiomyocyte transmembranes cultured with either PBMC/T. cruzi co-cultures (control: 24.33 ± 3.83; Chagas: 43.62 ± 5.08 fmol/mg, N = 7 for both) or their conditioned medium (control: 37.84 ± 3.84, N = 4; Chagas: 54.38 ± 6.28 fmol/mg, N = 20); 2) [³H]-leucine uptake was increased in cardiomyocytes co-cultured with PBMC/T. cruzi-conditioned medium (Chagas: 21,030 ± 2321; control 10,940 ± 2385 dpm, N = 7 for both; P < 0.05); 3) plasma IL-6 was increased in chagasic rats, IL-1â, was increased in both plasma of chagasic rats and in the culture medium, and TNF-á level was decreased in the culture medium. In conclusion, our results suggest that cytokines are involved in the up-regulation of mAChR in chronic Chagas disease.

La enfermedad de chagas induce una supersensibilidad colinergica muscarinica en ventrículo derecho de ratas chagásicas sprague dawley / Chagas's disease induce a muscarinie cholinergic supersensibility in right ventricle of chagas rats spargue dawley

La Enfermedad de Chagas constituye un problema de salud pública en Venezuela, cuyas alteraciones están representadas fundamentalmente por el desarrollo de miocardiopatías incapacitantes. En la actualidad, las causas de las miocardiopatías no son realmente conocidasy tampoco existe tratamiento; sin embargo, dentro de la teoria neurogénica se ha postulado que el Sistema Colinérgico est  involúcrado en su desarrollo. Con el fin de dilucidar el estado de Receptor Colinérgico Muscarínico (RCM) en ésta enfermedad, se establecieron dos grupos de animales: Control (ratas sanas) y Experimental (ratas con Enfermedad de Chagas en etapa crónica), posteriormente las ratas fueron sacrificadas, disecando en corazón Ventrículo Izquierdo (VI), Ventrículo Derecho (VD), Tabique Interventricular (TIV), Aurícula (Au) y en el encéfalo Tronco Encefálico (TE). Se determinó la cantidad de proteínas mediante el método de Lowry, la densidad de RCM y los efectos de agonistas (Carbacol) y antagonistas selectivos (Pirenzepina, Metoctramina, 4-DAMP y Tropicamida) por medio de ensayos de radioligandos usando [³H]-QNB como marcador radioactivo. Los resultados mostraron en TE una disminución significativa de la cantidad de proteínas en ratas con Enfermedad de Chagas; en VD se encontró una supersensibilidad significativa del RCM en ratas Chagásicas, mientras que en TIV, VI y Au no se observaron diferencias significativas entre ambos grupos. En las curvas de desplazamiento de [³H]-QNB por agonistas y antagonistas selectivos, no se encontraron diferencias significativas en el perfil de desplazamiento y en los valores de CI50, al comparar los dos grupos. En conclusión la expresión de proteínas y del RCM se encuentran alteradas en TE y VD, respectivamente.