Biological and Molecular Docking Evaluation of a Benzylisothiocyanate Semisynthetic Derivative From Moringa oleifera in a Pre-clinical Study of Temporomandibular Joint Pain.

Objective: Moringa oleifera possesses multiple biological effects and the 4-[(4'-O-acetyl-α-L- rhamnosyloxy) benzyl] isothiocyanate accounts for them. Based on the original isothiocyanate molecule we obtained a semisynthetic derivative, named 4-[(2',3',4'-O-triacetyl-α-L-rhamnosyloxy) N-benzyl] hydrazine carbothioamide (MC-H) which was safe and effective in a temporomandibular joint (TMJ) inflammatory hypernociception in rats. Therefore, considering that there is still a gap in the knowledge concerning the mechanisms of action through which the MC-H effects are mediated, this study aimed to investigate the involvement of the adhesion molecules (ICAM-1, CD55), the pathways heme oxygenase-1 (HO-1) and NO/cGMP/PKG/K+ ATP, and the central opioid receptors in the efficacy of the MC-H in a pre-clinical study of TMJ pain. Methods: Molecular docking studies were performed to test the binding performance of MC-H against the ten targets of interest (ICAM-1, CD55, HO-1, iNOS, soluble cGMP, cGMP-dependent protein kinase (PKG), K+ ATP channel, mu (µ), kappa (κ), and delta (δ) opioid receptors). In in vivo studies, male Wistar rats were treated with MC-H 1 µg/kg before TMJ formalin injection and nociception was evaluated. Periarticular tissues were removed to assess ICAM-1 and CD55 protein levels by Western blotting. To investigate the role of HO-1 and NO/cGMP/PKG/K+ ATP pathways, the inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823, or glibenclamide were used. To study the involvement of opioid receptors, rats were pre-treated (15 min) with an intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole, or norbinaltorphimine. Results: All interactions presented acceptable binding energy values (below -6.0 kcal/mol) which suggest MC-H might strongly bind to its molecular targets. MC-H reduced the protein levels of ICAM-1 and CD55 in periarticular tissues. ZnPP-IX, naloxone, CTOP, and naltrindole reversed the antinociceptive effect of MC-H. Conclusion: MC-H demonstrated antinociceptive and anti-inflammatory effects peripherally by the activation of the HO-1 pathway, as well as through inhibition of the protein levels of adhesion molecules, and centrally by µ and δ opioid receptors.

Oral administration of eucalyptol reduces cell migration and pain-like behavior in zymosan-induced arthritis mice

Abstract Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.

Gliclazide Prevents 5-FU-Induced Oral Mucositis by Reducing Oxidative Stress, Inflammation, and P-Selectin Adhesion Molecules.

Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1ß and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1-2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1-1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.

N-3 polyunsaturated fatty acids and clozapine abrogates poly I: C-induced immune alterations in primary hippocampal neurons.

The viral mimetic polyinosinic:polycytidylic acid (poly I:C) is an important tool to study the consequences of viral infection to the development of neuropsychiatric disorders. Here, based on the premise of omega-3 polyunsaturated fatty acids (n3 PUFAs) as supplemental treatment to antipsychotics in schizophrenia, we investigated the involvement of NFkB pathway in the effects of n3 PUFAs or of the atypical antipsychotic clozapine in hippocampal poly I:C-challenged neurons. Primary hippocampal neuronal cultures were exposed to n3 PUFAs (DHA4.35 µM/EPA7.10 µM, DHA 8.7 µM/EPA14.21 µM or DHA17.4 µM/EPA28.42 µM) or clozapine (1.5 or 3 µM) in the presence or absence of poly I:C. MTT assay revealed that poly I:C-induced reduction in cell viability was prevented by n3 PUFAs or clozapine. N3 PUFAs (DHA 8.7 µM/EPA14.21 µM) or clozapine (3 µM) significantly reduced poly I:C-induced increase in iNOS, NFkB (p50/p65), IL-6 and nitrite when compared to non-treated cells. Only n3 PUFAs prevented poly I:C-induced deficits in BDNF. On the other hand, poly I:C caused a marked reduction in DCX immunoexpression, which was prevented only by clozapine. Thus, n3 PUFAs and clozapine exert in vitro neuroprotective effects against poly I:C immune challenge in hippocampal neurons, by mechanisms possibly involving the inhibition of canonical NFkB pathway. The present study adds further evidences to the mechanisms underlying n3 PUFAs and clozapine neuroprotective effects against viral immune challenges. Since n3 PUFAs is a safe strategy for use during pregnancy, our results also add further evidence for the use of this supplement in order to prevent alterations induced by viral hits during this developmental period.

Major depression model induced by repeated and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and neuroprogressive alterations.

Major depressed patients show increased bacterial translocation with elevated plasma levels of lipopolysaccharide (LPS), which may trigger immune-inflammatory and neuro-oxidative responses. Recently, an animal model based on chronic LPS administration was developed which was associated with long-lasting depressive-like and neuro-oxidative alterations in female mice. The aim of the current study was to investigate behavioral, neuroimmune and neuroprogressive alterations in female mice 6 weeks after LPS chronic exposure. Female mice received increasing doses of LPS during 5 days at one-month intervals repeated for 4 consecutive months. Six weeks after the last LPS-exposure, we assessed behavioral despair and anhedonia, microglial activation, alterations in tryptophan, 5-HT, kynurenine, quinolinic acid (QUIN) levels and spermidine/spermine N1-acetyltransferase (SAT1) expression in the hippocampus, both with and without fluoxetine administration. Our results show that six weeks post-LPS, mice present behavioral despair and anhedonia in association with increased IBA1 expression (a microglia activation marker), NF-kB p65 and IL-1ß levels, indoleamine 2,3-dioxygenase (IDO1) mRNA expression, kynurenine, QUIN levels and QUIN/tryptophan ratio, and lowered tryptophan, 5-HT levels and SAT1 mRNA expression. Fluoxetine reversed the behavioral and neuroimmune alterations but had no effect in the reversal of IDO1 increased expression, QUIN levels and QUIN/tryptophan ratio. In conclusion, our results support the validity of the chronic LPS model of major depression and additionally shows its translational relevance with respect to neuroimmune and neuroprogressive pathways.

Protective effect of angiotensin II receptor blocker against oxidative stress and inflammation in an oral mucositis experimental model.

BACKGROUND: The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin II receptor antagonist, on oral mucositis (OM) experimental model. METHODS: Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg day 1 and 40 mg/kg day 2). Animals (n = 10/group) were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle 30 minutes before 5-FU injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of IL-1ß, TNF-α, IL-10, TGF-ß, macrophage migration inhibitory factor (MIF), SOD, MMP-2 and FGF-2. In addition, IL-1ß and TNF-α levels were evaluated by ELISA. Myeloperoxidase activity (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were investigated by spectroscopic UV/VIS analysis. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantify the expression of IL-1ß, TNF-α, NF-κBp65, MKP1 and ACE2. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 protein levels were analysed by Western blot. RESULTS: Treatment with 10 mg/kg Olme reduced ulceration, inflammatory cell infiltration, MPO activity, MDA levels, iNOS and ERK1/2 proteins levels, MIF expression and TNF-α and IL-1ß of levels and gene expression. These findings were associated with a significant increase in the immunostaining of IL-10, FGF-2 and TGF-ß. In addition, gene expression of IL-1ß, TNF-α, NF-κBp65 MKP1 and ACE2 was decreased. CONCLUSION: Olmesartan at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

Orientações familiares necessárias para uma alta hospitalar segura do recém-nascido prematuro: revisão integrativa / Family guidelines needed for a safe hospital of the premature newborn: integrative review

Objetivo: identificar o conhecimento disponível na literatura sobre os cuidados necessários a serem orientados à família do recém-nascido prematuro em sua preparação para a alta hospitalar. Método: revisão integrativa acerca dos cuidados necessários a serem orientados à família do recém-nascido em sua preparação para a alta hospitalar. Utilizaram-se as bases de dados Cinahl, Lilacs e Medline, de julho de 2012 a outubro de2015. Oitocentos e vinte e quatro (824) artigos foram encontrados, porém, apenas nove foram considerados aptos para a análise por atenderem aos critérios de inclusão do estudo. Resultados: os achados evidenciados foram divididos em dois eixos temáticos > e >. Conclusão: tal análise permitiu conhecer e descrever aspectos que permeiam o processo de transição do prematuro para o domicílio.

Contribuições da enfermagem na segurança do paciente da Unidade de Terapia Intensiva: uma revisão integrativa / Nursing contributions to the patient's safety in the Intensive Care Unit: an integrative review / Contribuciones de enfermería en la Unidad de Cuidados Intensivos de seguridad del paciente: una revisión integradora

Objetivo: analisar a produção científica de enfermagem sobre a segurança do paciente na unidade de terapia intensiva. Método: revisão integrativa realizada nas bases de dados CINAHL, LILACS e SCOPUS, utilizando os descritores: patient safety/segurança do paciente, intensive care unit/unidade de terapia intensiva and nursing/enfermagem. Resultados: foram incluídos 13 artigos, analisados a partir de seis categorias: << Segurança do paciente na prevenção de eventos adversos na enfermagem >>, << Segurança do paciente na administração segura de medicamentos >>, << Segurança do paciente na comunicação efetiva >>, << Segurança do paciente na padronização de procedimentos >>, << Segurança do paciente na prevenção de úlcera por pressão >> e << Segurança do paciente na prática da higienização das mãos >>. Conclusão: os estudos apontaram como contribuições a importância da padronização dos procedimentos e quanto a baixa evidência das publicações relacionadas à enfermagem.(AU)

Objective: to analyze the scientific production on nursing related to patient's safety in the intensive care unit. Method: an integrative review conducted in CINAHL LILACS and SCOPUS databases, using the keywords: patient safety/patient safety, intensive care unit/intensive care unit and nursing/nursing. Results: the study included 13 articles analyzed from six categories: << Patient's safety in the prevention of adverse events in nursing >>, << Patient's safety in the safe administration of medication >>, << Patient's Safety in effective communication >>, << patient's Safety in the standardization of procedures >>, << patient's safety in the prevention of pressure ulcers >> and << patient's safety in the practice of handwashing >>. Conclusion: the study showed how contributions the importance of standardization of procedures and the low evidence of publications related to nursing.(AU)

Objetivo: analizar la producción científica de la enfermería en la seguridad del paciente en la unidad de cuidados intensivos. Método: una revisión integradora realizada en las bases de datos CINAHL, LILACS y SCOPUS, usando las palabras clave: la seguridad del paciente/la seguridad del paciente, unidad de cuidados intensivos/unidad de cuidados intensivos y de enfermería/ enfermería. Resultados: el estudio incluyó 13 artículos analizados a partir de seis categorías: << La seguridad del paciente en la prevención de eventos adversos en ancianos >>, << La seguridad del paciente en la administración segura de medicamentos >>, << la seguridad del paciente en la comunicación efectiva >>, << seguridad del paciente en la normalización de los procedimientos >>, << la seguridad del paciente en la prevención de úlceras por presión >> y << la seguridad del paciente en la práctica de lavado de manos >>. Conclusión: el estudio mostró cómo las contribuciones de la importancia de la normalización de los procedimientos y la escasa evidencia de publicaciones relacionadas con la enfermería.(AU)

Papel da via S100B/RAGE/NFkB na patogênese da mucosite intestinal experimental por 5-fluorouracil desregulação de células gliais e de neurônios entéricos

5-Fluorouracil (5-FU) promotesintestinal mucositis and motility alterations. Themucositis affect about40% of patients receiving 5-FU and there arereports of patients presentingmucositis afterthe first dose. Under other inflammatory conditions, the S100βprotein is involved in the RAGE activation with subsequent NFκBtranslocation to the nucleus and transcription of TNF-αand iNOS. The enteric glial cells through several mediators, such asS100β, interact with the intestinal epithelial cells and enteric neurons. Therefore, the aim of this study was investigatethe effect of 5-FU in the enteric glial cells and neurons, as well as studythe role of the via S100β/RAGE/NFκB in the pathogenesis of the experimental intestinal mucositis. Swiss male mice received saline (control, 0.9%, i.p.) or5-FU (450 mg/Kg, i.p., single dose). After24h, mice weretreated with pentamidine, aS100 βinhibitor (P0.8 mg/Kg +5FU; P4 mg/Kg +5FU; or onlyP4mg/Kg, i.p.) during two days and euthanized on the fouth day of the experimental protocol...

O 5-Fluorouracil (5-FU) promove mucosite intestinal e alterações da motilidade.A mucositeatinge cerca de 40% dos pacientes em tratamento com5-FUe há relatos de pacientes que a apresentam na primeira dose administrada.Em outras condições inflamatórias, a proteína S100β está envolvida na ativação de RAGE com consequente translocação de NFκB para o núcleo e transcrição de TNF-αe de iNOS.As células gliais entéricas por meio deS100β,interagem com as células epiteliais intestinais e com os neurônios entéricos.Nesse contexto, oobjetivodeste estudo éinvestigar o efeito do5-FU nas células gliais e nos neurôniosentéricos, bem como estudar o papel da via S100β/RAGE/NFκB na patogênese da mucosite intestinal induzida por esse quimioterápico. Os camundongos Swiss machos receberam salina (0,9%, i.p.) ou 5-FU (450 mg/Kg, i.p. dose única). Após 24h da administração do quimioterápico, administrou-se pentamidina, inibidor de S100β (P0,8 mg/Kg +5FU; P4 mg/Kg +5FU; ou somente P4mg/Kg, i.p.) durante dois dias e os animais foram eutanasiadosno quarto dia do protocolo experimental...

Educação em saúde com adolescentes acerca do uso de álcool e outras drogas / Health education about alcohol and other drugs for adolescents

O estudo objetivou descrever uma estratégia educativa em saúde acerca do uso de álcool e outras drogas junto a umgrupo de adolescentes. Trata-se de um estudo descritivo que relata a vivencia de acadêmicas de enfermagem nodesenvolvimento de estratégia educativa em uma escola do município de Caucaia, Estado do Ceará-Brasil. A estratégiacontou com a participação de 43 jovens com idades entre 15 e 16 anos. Os quatro momentos foram nomeados de formadidática: socialização, abordagem da temática, desenvolvimento da arte, e debate sobre a arte desenvolvida. Asocialização dos conteúdos expressos nos desenhos e na música elaborada promoveu uma maior interação entre osenvolvidos, fato evidenciado pela maior participação dos adolescentes e pelas indagações dos mesmos em relação aotema. Neste sentido, é importante destacar que o enfermeiro, como promotor de saúde, deve estar mais presente noambiente escolar, de forma a promover uma maior interação da escola com o setor saúde, sensibilizando assim os sujeitospara as causas e as consequências do uso das drogas...

This study aimed to describe a health education strategy about alcohol and other drugs for a group of adolescents. This isa descriptive study reports the experience of nursing students in developing an education strategy at a school in the cityof Caucaia, Ceará, Brazil. The workshop had the participation of 43 adolescents, between 15 and 16 years old. Theeducational activity was divided into four stages, didactically named: socialization, thematic approach, developing art,and debating on the art developed. The socialization of contents expressed in the drawings and music which were createdpromoted greater interaction among participants, evidenced by increased participation of the adolescents. The nurse ashealth promoter needs to act in the school environment, practicing transdisciplinarity and intersectionality, raisingawareness of the subjects about the causes and consequences of drug abuse...

El estudio tuvo como objetivo describir una estrategia de educación sobre el uso del alcohol y de otras drogas con ungrupo de adolescentes. Se trata de un estudio descriptivo de informes de la experiencia de los estudiantes de enfermeríaen el desarrollo de una estrategia educativa llevada a cabo en una escuela ubicada en Caucaia, Ceará, Brasil. Laestrategia tuvo la participación de 43 jóvenes con edades entre 15 y 16 años. Se dividieron en cuatro etapas, llamadasdidácticamente: socialización, enfoque temático, desarrollo del arte y un debate sobre las artes desarrolladas. Lasocialización de los contenidos expresados en los dibujos y en la canción elaborada han promovido más interacción entrelas partes involucradas, lo que se evidencia por el aumento de la participación de los adolescentes y consultas sobre adicho tema. En este sentido, es importante resaltar que el enfermero como promotor de la salud debe estar más presenteen el ámbito escolar con el fin de promover más interacción de la escuela con el sector salud, y sensibilizar así, lossujetos a las causas y consecuencias de la adicción a las drogas...