Experimental acute anti-inflammatory activity of preparations with complexed cannabidiol in carriers

Abstract Cannabidiol (CBD) is a bioactive compound with promising anti-inflammatory results but has low aqueous solubility. Complexation of drugs with this characteristic in carriers is an alternative to improve their efficiency. This study aimed to prepare and characterize CBD complexes in different carriers, and to evaluate the anti-inflammatory effect of such preparations using an experimental model of edema induction in rat paws. The results were compared to a reference drug, ibuprofen (IBU). The carriers evaluated were beta cyclodextrin (bCD) and activated charcoal (AC). Quantification of the drugs in the complexes was determined, and different qualitative analyses were also performed. Oral treatments in single doses with CBD showed inhibitory effects similar to that of IBU, potentiating its bioactivity without significant adverse effects. CBD*bCD doses at 4.375, 8.75, 17.5, and 35 mg/kg significantly reduced the intensity of edema compared to equivalent doses of pure bioactive. In contrast, CBD*AC did not generate benefits. There was no significant inhibitory effect on myeloperoxidase activity, requiring more specific analyses to assess this parameter. The results suggest that the CBD*bCD complexation is perfectly feasible, increasing its anti-edematogenic efficacy in the experimental model used.

Efeitos da nanopartícula de ácido poli lático-co-glicólico (PLGA) associada ao cloridrato de metformina na doença periodontal em ratos diabéticos / Effects of polylactic-co-glycolic acid (PLGA) nanoparticle associated with metformin hydrochloride on periodontal disease in diabetic rats

Existe uma associação entre diabetes e a periodontite, e a Metformina (MET) além de controlar os níveis glicêmicos, tem apresentado efeitos antiinflamatórios e na diminuição da perda óssea periodontal. Ao se veicular a MET a um sistema de nanopartículas pode-se apresentar a vantagem de aumento da eficácia terapêutica. Objetivos: esse estudo consistiu na avaliação dos efeitos antiinflamatórios, perda óssea e disponibilidade in vitro/in vivo de uma nanopartícula de ácido poli lático-co-glicólico (PLGA) associada à MET em um modelo de periodontite induzida por ligadura. Materiais e métodos: o PLGA carreado com diferentes doses da MET foi caracterizado pelo seu diâmetro médio, tamanho da partícula, índice de polidispensão e eficiência de aprisionamento. Foram utilizados ratos machos da linhagem Wistar, divididos aleatoriamente, em grupos controles e experimentais com diferentes doses de MET associadas ou não ao PLGA, os quais receberam diferentes tratamentos. Amostras de maxilas e tecidos gengivais foram utilizadas para avaliação de perda óssea e inflamação, por meio da microtomografia computadorizada, histopatológico, imunohistoquímica, análise de citocinas inflamatórias e expressão gênica de proteínas por RT-PCR quantitativo. Para o ensaio de liberação in vitro, utilizou-se o dispositivo de células de difusão vertical de Franz estáticas. Para a disponibilidade in vivo, as amostras de sangue foram coletadas em diferentes intervalos de tempo e analisadas por cromatografia líquida de alta eficiência acoplado a espectrometria de massas (HPLC-MS/MS). Resultados: o diâmetro médio das nanopartículas de PLGA carreadas com MET estava em um intervalo de 457,1 ± 48,9 nm (p <0,05) com um índice de polidispersidade de 0,285 (p <0,05), potencial Z de 8,16 ± 1,1 mV (p <0,01) e eficiência de aprisionamento (EE) de 66,7 ± 3,73. O tratamento com a MET 10 mg / kg + PLGA mostrou uma baixa concentração de células inflamatórias, fraca imunomarcação para RANKL, Catepsina K, OPG e osteocalcina. Diminuição dos níveis de IL-1ß e TNF-α (p <0,05), aumento da expressão gênica do AMPK (p <0,05) e diminuição do NF-κB p65, HMGB1 e TAK-1 (p <0,05). O 10 mg/kg MET + PLGA foi liberado no ensaio in vitro sugerindo um modelo cinético de difusão parabólica com um perfil de liberação que atinge 50% de seu conteúdo em 2h e permanece em liberação constante em torno de 60% até o final de 6h. O ensaio in vivo mostrou o volume aparente de distribuição Vz/F (10 mg/kg MET + PLGA, 46,31 mL/kg vs. 100 mg/kg MET + PLGA, 28,8 mL/kg) e o tempo médio de residência MRTinf (PLGA + MET 10 mg /kg, 37,66h vs. MET 100 mg/kg, 3,34h). Conclusão: o PLGA carreado com MET diminuiu a inflamação e a perda óssea na periodontite em ratos diabéticos. O 10 mg/kg MET + PLGA teve uma taxa de eliminação mais lenta em comparação com o MET 100 mg/kg. A formulação modifica os parâmetros farmacocinéticos, como volume de distribuição aparente e tempo médio de residência (AU).

There is an association between diabetes and periodontitis, and Metformin (MET) in addition to controlling glycemic levels, has shown anti-inflammatory effects and decreased periodontal bone loss. By transferring MET to a nanoparticle system, the advantage of increasing therapeutic efficacy can be presented. Objectives: this study consisted of evaluating the antiinflammatory effects, bone loss and in vitro/in vivo availability of a polylactic-co-glycolic acid (PLGA) nanoparticle associated with MET in a ligature-induced periodontitis model. Materials and methods: PLGA loaded with different doses of MET was characterized by its mean diameter, particle size, polydispension index and entrapment efficiency. Male Wistar rats were used, randomly divided into control and experimental groups with different doses of MET associated or not with PLGA, which received different treatments. Samples of jaws and gingival tissues were used to assess bone loss and inflammation, using computed microtomography, histopathology, immunohistochemistry, analysis of inflammatory cytokines and gene expression of proteins by quantitative RT-PCR. For the in vitro release assay, the static Franz vertical diffusion cell device was used. For in vivo availability, blood samples were collected at different time intervals and analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Results: the mean diameter of MET-loaded PLGA nanoparticles was in the range of 457.1 ± 48.9 nm (p <0.05) with a polydispersity index of 0.285 (p <0.05), Z potential of 8.16 ± 1.1 mV (p <0.01) and trapping efficiency (EE) of 66.7 ± 3.73. Treatment with MET 10 mg/kg + PLGA showed a low concentration of inflammatory cells, weak immunostaining for RANKL, Cathepsin K, OPG and osteocalcin. Decreased IL-1ß and TNF-α levels (p <0.05), increased AMPK gene expression (p <0.05) and decreased NF-κB p65, HMGB1 and TAK-1 (p <0. 05). The 10 mg/kg MET + PLGA was released in the in vitro assay suggesting a kinetic model of parabolic diffusion with a release profile that reaches 50% of its content in 2h and remains in constant release around 60% until the end of 6h . The in vivo assay showed the apparent volume of distribution Vz/F (10 mg/kg MET + PLGA, 46.31 mL/kg vs. 100 mg/kg MET + PLGA, 28.8 mL/kg) and the mean MRTinf residency (PLGA + MET 10 mg/kg, 37.66h vs. MET 100 mg/kg, 3.34h). Conclusion: MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats. 10 mg/kg MET + PLGA had a slower rate of elimination compared to 100 mg/kg MET. The formulation modifies pharmacokinetic parameters such as apparent volume of distribution and mean residence time (AU).

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

The role of jaboticaba (Plinia jaboticaba (VELL. ) Berg) phenolic compounds in obesity-associated intestinal inflammation / O papel dos compostos fenólicos da jabuticaba (Plinia jaboticaba (VELL. ) Berg) na inflamação intestinal associada à obesidade

Jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian native fruit belonging to the Myrtaceae family. Previously it was demonstrated that phenolicrich extracts from jaboticaba (PEJ) possess health-beneficial properties in dietinduced obesity; however, whether PEJ modulates the obesity-associated intestinal inflammatory status remains unclear. The objective of the present study was to evaluate the effect of PEJ on intestinal inflammation associated with obesity induced by a high-fat-sucrose (HFS) diet. Thus, forty male C57BL/6J mice were distributed into two groups: negative control (CH, 10 animals), fed standard diet AIN96M and water ad libitum; and positive control (HFS, 30 animals), fed HFS diet and water ad libitum induced to obesity for an initial period of 14 weeks. After this period, the HFS group was redistributed in three groups of 10 animals each, and continuously fed HFS diet for another 14 weeks: HFS group received daily gavages of water, PEJ1 group received PEJ at the dose of 50 mg of gallic acid equivalent (GAE)/kg body weight (BW and PEJ2 group received PEJ at the dose of 100 mg GAE/kg BW. Feed intake and body mass were monitored weekly, and fasting glucose biweekly. The initial period of obesity-induction demonstrated that the HFS diet was efficient to promote a significant body weight gain and fasting hyperglycemia when compared to the negative control group (CH). At the end of the experiment the animals were euthanized under anesthesia and their organs and tissues were collected. The major classes of phenolic compounds found in PEJ were ellagitannins, anthocyanins including cyanidin and delphinidin glycosides, proanthocyanidins, and free ellagic acid. PEJ-treated animals presented a reduced body weight gain, adiposity and demonstrated significant reversion of insulin resistance and dyslipidemia. In addition, the inflammatory profile of colon demonstrated that PEJ prevented metabolic endotoxemia linked to an attenuation of the HFS diet-induced intestinal inflammation via downregulation of pro-inflammatory mediators such as tumor necrosis factor (TNF-ß), membrane transporter toll-like receptor-4 (TLR-4) and nuclear factor-κB (NF-κB) in the colon. These anti-inflammatory effects appear to be involved, at least in part, with an inhibition of the colonic inflammasome pathway of obese mice. Collectively, our data reveals that PEJ exerts a direct anti-inflammatory effect in obesity-associated intestinal inflammation and this outcome is linked to an amelioration of metabolic endotoxemia in obese mice

A jabuticaba (Plinia jaboticaba (Vell.) Berg) é uma fruta nativa brasileira pertencente à família Myrtaceae. Anteriormente, foi demonstrado que extratos ricos em fenólicos de jabuticaba (PEJ) possuem propriedades benéficas à saúde na obesidade induzida por dieta; no entanto, se o PEJ modula o estado inflamatório intestinal associado à obesidade ainda não está claro. O objetivo do presente estudo foi avaliar o efeito do PEJ na inflamação intestinal associada à obesidade induzida por uma dieta rica em sacarose (HFS). Assim, quarenta camundongos C57BL / 6J machos foram distribuídos em dois grupos: controle negativo (CH, 10 animais), alimentados com dieta padrão AIN96M e água ad libitum; e controle positivo (HFS, 30 animais), alimentado com dieta HFS e água ad libitum induzida à obesidade por um período inicial de 14 semanas. Após este período, o grupo HFS foi redistribuído em três grupos de 10 animais cada, e continuamente alimentado com dieta HFS por mais 14 semanas: o grupo HFS recebeu gavagens diárias de água, o grupo PEJ1 recebeu PEJ na dose de 50 mg de ácido gálico equivalente (GAE) / kg de peso corporal (pc) e o grupo PEJ2 recebeu PEJ na dose de 100 mg GAE / kg pc. O consumo de ração e a massa corporal foram monitorados semanalmente e a glicemia de jejum quinzenal. O período inicial de indução da obesidade demonstrou que a dieta HFS foi eficiente em promover significativo ganho de peso corporal e hiperglicemia de jejum quando comparada ao grupo controle negativo (HC). Ao final do experimento os animais foram submetidos à eutanásia sob anestesia e seus órgãos e tecidos coletados. As principais classes de compostos fenólicos encontrados em PEJ foram elagitaninos, antocianinas incluindo cianidina e delfinidina glicosiladas, proantocianidinas e ácido elágico livre. Os animais tratados com PEJ apresentaram redução do ganho de peso corporal, adiposidade e reversão significativa da resistência à insulina e dislipidemia. Além disso, o perfil inflamatório do cólon demonstrou que o PEJ evitou a endotoxemia metabólica ligada a uma atenuação da inflamação intestinal induzida pela dieta de HFS por meio da regulação negativa de mediadores pró-inflamatórios, como o fator de necrose tumoral (TNF-), transportador de membrana toll- como o receptor 4 (TLR-4) e o fator nuclear B (NF-B) no cólon. Esses efeitos anti-inflamatórios parecem estar envolvidos, pelo menos em parte, com uma inibição da via do inflamassoma colônico de camundongos obesos. Coletivamente, nossos dados revelam que o PEJ exerce um efeito anti-inflamatório direto na inflamação intestinal associada à obesidade e esse resultado está relacionado com uma melhora da endotoxemia metabólica em camundongos obesos

Antinociceptive and anti-inflammatory effects of cellular and extracellular extracts from microalga Chlamydomonas pumilioniformis on mice

Microalga species have attracted interest as a source of bioactive compounds with several pharmacological activities. Previous studies reported that microalgae from the genus Chlamydomonas have anti-inflammatory and antioxidant properties. In this study, antinociceptive and anti-inflammatory activities of two extracts from microalga Chlamydomonas pumilioniformis were investigated. Cellular and extracellular extracts were prepared from a 14 day-batch culture in WC medium at the end of exponential growth and their carbohydrate contents were determined. Antinociceptive effects of extracts were evaluated by writhing and formalin-induced nociception tests, while the anti-inflammatory activity was analyzed by formalin-induced paw edema in mice. The analysis of dissolved carbohydrates detected amounts of 90 and 20 µg mL-1 of total carbohydrate in cellular and extracellular extracts, respectively. Cellular extract was mainly composed of glucose, but with significant proportions of arabinose, galactose and mannose and/or xylose and minor ones of fucose, rhamnose, amino sugars and uronic acids. Extracellular extract was composed of a similar proportion of glucose, galactose and mannose/xylose, besides significant ones of arabinose, fucose and galacturonic acid. Intraperitoneal administration of extracts significantly reduced writhing response in mice. In the formalin test, the extracellular extract inhibited both formalin phases, while the cellular extract was only effective in the late phase. Furthermore, extracts reduced the formalin-induced paw edema. In sum, we showed, for the first time, that C. pumilioniformis can be an important source of polysaccharides with anti-inflammatory and antinociceptive effects.

Hidroxicloroquina: Mensajes desde la cardiología en tiempos de pandemia por Coronavirus / Hydroxychloroquine. Cardiology's viewpoint in times of coronavirus pandemic

Ante la pandemia de COVID-19 (del inglés coronavirus disease 2019), uno de los fármacos propuesto para su tratamiento es la hidroxicloroquina. Se revisan aquí aspectos cardiológicos del uso de cloroquina e hidroxicloroquina. Se realizó una revisión no sistemática en la literatura médica orientada a la búsqueda de información acerca de su seguridad y eficacia como antimaláricos y antivirales, así como en el tratamiento prolongado de enfermedades reumatológicas. Se halló un efecto antiinflamatorio con reducción de eventos cardiovasculares a largo plazo, una cardiopatía muy infrecuente por un efecto lisosomal del fármaco, y a nivel hemodinámico hipotensión, taquicardia, y prolongación del intervalo QT, exacerbado si se combina con azitromicina. Sin embargo, la tasa de eventos adversos cardíacos de la hidroxicloroquina y la cloroquina fue baja.

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of long-term cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.

Uso de fármacos anticorpos monoclonais, imunomoduladores e anti-inflamatórios no tratamento da infecção por COVID-19 / Use of monoclonal antibodies, immunomodulators, and anti-inflammatory drugs in the treatment of COVID-19

O objetivo deste estudo foi realizar o levantamento bibliográfico de artigos científicos e ensaios clínicos sobre a utilização de anticorpos monoclonais, imunomoduladores e anti-inflamatórios como possíveis alternativas terapêuticas para uso em pacientes com COVID-19, com ênfase nos mecanismos de ação e resultados de ensaios clínicos. Foram analisados artigos obtidos na base de dados MEDLINE® e ensaios clínicos disponíveis no site ClinicalTrials no período de 6 de abril a 6 de maio de 2020. Os ensaios realizados com os fármacos apresentados nesta revisão bibliográfica sugerem a viabilidade de uso de algumas dessas drogas como alternativas para tratamento da COVID-19. No entanto, observou-se que, em função do número reduzido de participantes dos estudos disponíveis, é indispensável a continuidade de pesquisas e dos ensaios clínicos com esses medicamentos, para estimar a eficácia dessas drogas no tratamento do SARS-CoV-2, contra o qual ainda não há terapia específica

The objective of this study was to carry out a bibliographic survey of scientific articles and current clinical trials on the use of monoclonal antibodies, immunomodulators, and anti-inflammatories as possible therapeutic alternatives for use in patients with COVID-19, highlighting their mechanisms of action and results of clinical trials. Articles from the MEDLINE® database and clinical trials available on the ClinicalTrials website were analyzedThe tests performed with the drugs presented in this bibliographic review suggest the feasibility of using some of these drugs as treatment alternatives for COVID-19. However, it was observed that the small samples evaluated in these tests make it imperative to proceed with research and clinical trials with these drugs to provide greater evidence of the effectiveness of these drugs in the treatment of the disease caused by SARS-CoV-2, for which there is no specific therapy so far.

Potential and clinical relevant drug-drug interactions among elderly from nursing homes: a multicentre study in Murcia, Spain / Interações medicamentosas potenciais e clinicamente relevantes em instituições de longa permanência para idosos: um estudo multicêntrico em Murcia, Espanha

Abstract This study purposes to determine the prevalence of potential and clinical relevant Drug-Drug-Interactions (pDDIs) in institutionalized older adults and to identify the pertinent factors associated. We conduct an observational, multicenter and cross-sectional study during the last quarter of 2010. We selected a sample of 275 subjects (aged ≥ 65 years) from 10 nursing homes of Murcia (Spain) by a two-stage complex sampling. pDDIs were identified using the College of Pharmacists Database. We only considered pDDIs of clinical relevance, and thereafter the relevant factors were identified through uni-level and multi-level regression analyses. A total of 210 pDDIs were identified, 120 of which were considered clinically relevant (57.1%), affecting a total of 70 elderly (25.8%). Eight pharmacological groups made up 70.2% of the clinically relevant pDDIs. More clinically relevant DDIs were found in people suffering several pathologies (OR = 2.3; 95%CI = 1.4-4.5), and also in people who take ten or more drugs daily (OR = 9.6; 95%CI = 4.8-19.1), and people who take anti-inflammatory drugs (OR = 3.9; 95%CI = 1.4-10.4). This study reveals that clinically relevant pDDIs are very common in institutionalized elderly people, and that caregivers should aim at improving their practice in order to reduce the prevalence of this phenomenon.

Resumo Este estudo pretende identificar a prevalência de interações medicamentosas potenciais (IMP) em idosos institucionalizados e seus fatores associados. Realizamos um estudo observacional, multicêntrico e transversal, durante o último trimestre de 2010. Selecionamos uma amostra de 275 sujeitos (≥ 65 anos) de 10 instituições para idosos de Murcia (Espanha) mediante amostragem aleatória complexa em duas etapas. As IMP foram identificadas usando a base de dados do College of Pharmacists. Estimamos a prevalência de IMP de relevância clínica e analisamos os fatores associados com análise de regressão uni e multinível. Identificamos 210 IMP, das quais 120 foram consideradas clinicamente relevantes (57,1%) e afetaram 70 idosos (25,8%). Oito grupos farmacológicos constituíram 70,2% das IMP clinicamente relevantes. A prevalência de IMP esteve associada à multimorbidade (OR = 2,3; IC 95% = 1,4-4,5) e tomar dez ou mais medicamentos diariamente (OR = 9,6; IC95% = 4,8-19,1) e uso de medicamentos anti-inflamatórios (OR = 3,9; IC 95% = 1,4-10,4). Este estudo revela que as IMP clinicamente relevantes são muito comuns em idosos institucionalizados e que os serviços devem melhorar seus processos para reduzir a prevalência deste fenômeno.

Effect of iguratimod on diclofenac metabolism by CYP2C9 in rats and human recombinant CYP2C9 yeast cells

Iguratimod (IGU, also known as T-614), a novel disease modifying antirheumatic drug intended to cure patients with rheumatoid arthritis (RA). The purpose of this study is to evaluate the effect of IGU on the pharmacokinetics of CYP2C9 probe drug diclofenac and its metabolite 4′-hydroxy diclofenac in vivo and in vitro. In in vivo experiments, 24 rats were randomly assigned to three groups consisting of the control group (Normal saline), low dose IGU group (10 mg/kg) and high dose IGU group (30 mg/kg). Blood samples were collected from orbital sinuses vein before 1 hour and serial times of giving diclofenac (15 mg/kg) to all the rats. Plasma concentration of diclofenac and its metabolite 4´-hydroxy diclofenac were assayed by high performance liquid chromatography. Pharmacokinetic parameters were assessed by Winnonlin 6.4 pharmacokinetic software. Moreover, in vitro studies were performed in recombinant human CYP2C9 yeast cell system. IGU at low dose showed no significant differences in the pharmacokinetic parameters of diclofenac and 4-hydroxy diclofenac in vivo when compared with control group (p>0.005). However, at the high dose of IGU, the pharmacokinetic parameters of 4´-hydroxy metabolite of diclofenac increase in half-life (T1/2) and mean area under the curve (AUC0→24), while a decrease in mean clearance (CL, mL/h/kg) and volume of distribution Vz (mL/kg). In addition, in in vitro study, high doses of IGU reduces the metabolism rate of diclofenac. IGU at high dose significantly increase the pharmacokinetics parameters of 4´-hydroxy diclofenac in rats. Additionally, it also showed the potent inhibitory effect on diclofenac metabolism in recombinant human CYP2C9 yeast cells.

Avaliação in vitro do potencial cariogênico e erosivo de corticosteroide de uso tópico / In vitro evaluation of cariogenic and erosive potential of topic corticosteroid

Introdução: o tratamento com bochechos de dexametasona elixir é bastante descrito na literatura para casos de lesões erosivas e ulceradas em mucosa bucal. Excipientes acrescentados aos medicamentos os tornam mais palatáveis e estáveis, embora possam resultar em efeitos adversos que comprometem a saúde bucal. Objetivo: este estudo propôs-se a avaliar, in vitro, o pH, a acidez total titulável (ATT) e o teor de sólidos solúveis totais (SST) de diferentes marcas de dexametasona elixir disponíveis no mercado da cidade de Salvador, correlacionando-os ao potencial erosivo e cariogênico do medicamento para os dentes. Metodologia: seis marcas (A, B, C, D, E e F) de laboratórios distintos foram incluídas neste estudo. O valor do pH foi aferido utilizando-se pHmetro e agitador magnético; a ATT foi determinada adicionando-se hidróxido de sódio (NaOH) 0,1 N e a aferição do SST foi através de refratômetro. Os dados foram expressos em valores médios e desvios padrão. Resultados: o pH de todas as marcas investigadas apresentou medidas abaixo de 5,5, logo, todas apresentaram potencial erosivo. Na avaliação da ATT, maior volume de NaOH 0,1N foi necessário pela marca D para alcançar pH 5,5 e 7,0. Dentre as marcas investigadas, a marca B foi a que apresentou maior teor de SST em sua composição. Conclusão: soluções para uso local de dexametasona elixir possuem potencial erosivo e alto teor de SST, tornando-se, então, importante a orientação de instrução de higiene oral dos pacientes que possuem maior risco de desenvolver alterações dentárias.

Introduction: treatment with mouthwash dexamethasone elixir is sufficiently described in the literature for cases of erosive and ulcerated lesions in oral mucosa. Excipients added to drugs make them more palatable and stable, however, may result in adverse effects that compromise the health of the oral cavity. Aim: this study sets out to evaluate in vitro pH, titratable total acidity (TTA) and the total soluble solids content (TSS) of different brands of dexamethasone elixir available on the market of Salvador city, correlating them to the potential of cariogenic and erosive medicine for the dental units. Methodology: six distinct laboratories brands (A, B, C, D, E and F) were included in this study. The pH value was assessed using a pH meter and magnetic stirrer, the TTA was determined by adding sodium hydroxide (NaOH) 0.1 N and measurement of TSS was made with refractometer. The data were expressed as average and standard deviations. Results: the pH of all brands investigated presented measures below 5.5, so, all presented erosive potential. In TTA, greater volume of NaOH 0, 1N was required by D brand to achieve pH 5.5 and 7.0. Among the brands investigated, brand B was the one that presented the highest content of TSS in its composition. Conclusion: solutions for local use of dexamethasone elixir have erosive potential and high content of TSS, becoming so important the guidance of oral hygiene instruction of patients who have higher risk of developing dental changes

Pleomorphic undifferentiated soft tissue sarcoma in patient with long standing inflammatory bowel disease

Inflammatory bowel disease (IBD) has been associated with the development of both gastrointestinal and extraintestinal malignancy. The role of therapy in the development of malignancy in IBD has been controversial. We present the case of a 40-year-old female patient with long-standing mild IBD, who developed an undifferentiated pleomorphic sarcoma of the inguinal region and provide a brief review of the relevant literature. While our case likely represents a coincidence of two unrelated pathological entities, clinicians should keep in mind the possibility of soft tissue sarcomas in patients chronically treated with anti-inflammatory agents.

Síndrome de Cushing iatrogénico en un lactante por uso prolongado de corticoides tópicos: reporte de caso / Iatrogenic Cushing's syndrome in a infant due to prolonged use of topical corticosteroids: case report

INTRODUCCIÓN: El síndrome de Cushing (SC) es una patología endocrinológica por exceso de glucocorticoides, dependiente o independiente de hormona corticotropina (ACTH). La principal causa es iatrógenica por uso excesivo de glucocorticoides. OBJETIVO: Evidenciar la asociación entre uso prolongado de corticoides tópicos y desarrollo de SC. CASO CLÍNICO: Lactante mayor previamente sano, quien recibió tratamiento con corticoides tópicos debido a dermatitis seborreica. Debido a uso prolongado no supervisado, evolucionó con síndrome de Cushing caracterizado por obesidad y compromiso de la velocidad de crecimiento. Se suspendió uso tópico y se inició terapia en dosis de sustitución fisiológica en descenso, logrando mejoría clínica. DISCUSIÓN: Los corticoides tópicos se utilizan ampliamente en la práctica clínica para manejo de patologías dermatológicas. Éstos se encuentran disponibles en diversas presentaciones y potencias. Los principales factores determinantes en su acción son: características de la piel, principio activo del medicamento, potencia y técnica de aplicación, por lo que los efectos adversos se observan con mayor frecuencia ante uso por dermatitis del pañal. El principal efecto adverso del uso prolongado es el desarrollo del síndrome de Cushing, pudiendo prevenirse mediante uso supervisado y descenso progresivo. CONCLUSIÓN: Resulta funda mental el uso racional y cuidadoso de los corticoides tópicos para aprovechar los efectos beneficiosos y evitar la aparición de reacciones adversas.

INTRODUCTION: Cushing's syndrome (CS) is an endocrine disease by to glucocorticoids excess, depen dent or independent of adrenocorticotropic hormone (ACTH). The main cause is iatrogenic due to excessive use of glucocorticoids. OBJECTIVE: To show the association between prolonged use of topical corticosteroids and the development of CS. CLINICAL CASE: An infant treated with topical cor ticosteroids due to seborrheic dermatitis. Due to long-term unsupervised use, he develops Cushing's syndrome characterized by obesity and compromised growth rate. Topical use of corticosteroids was discontinued and physiological replacement therapy was initiated with descending doses, achieving clinical improvement. DISCUSSION: Topical corticosteroids are widely used in clinical practice for management of dermatological pathologies. These are available in various presentations with va riable efficiency. The main determining factors in its action are the characteristics of the skin, the active principle of the drug, the potency and application technique, so that the adverse effects are observed more frequently in the use due to diaper dermatitis. The main adverse effect of long-term use is Cushing's syndrome which can be prevented through supervised use and progressive decrease. CONCLUSION: The rational and careful use of topical corticosteroids is essential to take advantage of the beneficial effects and avoid adverse effects.

Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations ≥ 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential

Perfil de segurança da terapia anti-TNF na doença de Crohn: um estudo observacional brasileiro comparativo entre infliximabe e adalimumabe / Safety profile of anti-tnf therapy in crohn's disease management: a brazilian single-center direct retrospective comparison between infliximab and adalimumab

ABSTRACT BACKGROUND: Infliximab and adalimumab are considered effective drugs in the management of Crohn's disease. However, due to significant immunossupression, they can cause important adverse events, mostly infections. OBJECTIVE: The aim of this study was to quantify and describe adverse events derived from adalimumab and infliximab use in Crohn's disease patients, and to compare the safety profile between these two agents. METHODS: This was an observational, single-center, longitudinal, retrospective study with Crohn's disease patients under infliximab or adalimumab therapy. Variables analyzed: demographic characteristics (including the Montreal classification), type of agent used, concomitant immunomodulators, presence and types of adverse events observed. Patients were allocated in two groups (infliximab and adalimumab) and had their adverse events accessed and subsequently compared. RESULTS: A total of 130 patients were included (68 in infliximab and 62 in adalimumab groups, respectively). The groups were fully homogeneous in all baseline characteristics, with a median follow-up of 47.21±36.52 months in the infliximab group and 47.79±35.09 in the adalimumab group (P=0.512). Adverse events were found in 43/68 (63.2%) and 40/62 (64.5%) in each group, respectively (P=0.879). There were no differences between the groups regarding infections (P=0.094) or treatment interruption (P=0.091). There were higher rates of infusion reactions in the infliximab group (P=0.016). Cephalea and injection site reactions were more prevalent in adalimumab patients. CONCLUSION: Adverse events were found in approximately two thirds of Crohn's disease patients under anti-TNF therapy, and there were no significant differences between infliximab or adalimumab.

RESUMO CONTEXTO: A utilização de inibidores do fator de necrose tumoral (TNF) alfa no manejo da doença de Crohn é cada vez mais frequente. Tanto o infliximabe quanto o adalimumabe são considerados medicamentos efetivos no controle da doença. Entretanto, por serem potentes imunossupressores, podem causar efeitos adversos importantes, principalmente infecções. OBJETIVO: O objetivo primário deste estudo foi analisar a presença de efeitos adversos dos anti-TNFs em portadores de doença de Crohn, comparando-se infliximabe e adalimumabe e individualizando-se o perfil de segurança de cada droga. MÉTODOS: Estudo observacional, longitudinal e retrospectivo, que incluiu portadores de doença de Crohn com uso de infliximabe ou adalimumabe de uma coorte de pacientes tratados em um único centro. Analisou-se características demográficas (incluindo-se a classificação de Montreal), tipo de agente utilizado, presença e tipo dos eventos adversos observados, entre outras variáveis. Os pacientes foram alocados em dois grupos (infliximabe e adalimumabe) e tiveram os efeitos adversos anotados e posteriormente comparados. RESULTADOS: Um total de 130 pacientes foram incluídos (68 com infliximabe e 62 com adalimumabe). Os grupos foram homogêneos em todas as variáveis analisadas, com tempo de seguimento médio de 47,21±36,52 meses no grupo infliximabe e 47,79±35,09 no grupo adalimumabe (P=0,512). Efeitos adversos foram encontrados em 43/68 (63,2%) e 40/62 (64,5%) nos dois grupos, respectivamente (P=0,879). Não houve diferença entre os grupos em relação a infecções (P=0,094) ou interrupção do tratamento (P=0,091). Houve maiores índices de reações infusionais no grupo infliximabe (P=0,016). Cefaleia e reações no local das injeções foram mais frequentes no grupo adalimumabe. CONCLUSÃO: Efeitos adversos foram encontrados em cerca de dois terços dos pacientes com doença de Crohn em uso de anti-TNF, não havendo maiores diferenças em relação ao uso de infliximabe ou adalimumabe.

Incidence of anterior segment neovascularization during intravitreal treatment for macular edema secondary to central retinal vein occlusion / Incidência de neovasos de segmento anterior durante o tratamento de edema macular secundário a oclusão da veia central da retina

ABSTRACT Purpose: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study. The primary outcome was the incidence rate of ASN at month 6. The secondary outcomes were the mean changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography over time to month 12. Results: ASN developed in 8 (22.86%) eyes, including 5 (62.50%) eyes in the sham group and 3 (37.50%) eyes in the IVTA group, during 12 months of fol low-up (p=0.009). BCVA differed significantly (p<0.05) among the groups only at month 1. CFT did not differ significantly (p<0.05) among the groups over 12 months. NVG required surgery and developed in one eye despite laser treatment. Conclusion: Early treatment with intravitreal antivascular endothelial growth factor therapy decreases the rates of ASN and NVG after CRVO.

RESUMO Objetivo: Analisar as taxas de incidência de neovascularização do segmento anterior (NSA) e de glaucoma neovascular (GNV), em pacientes com edema macular secundário a oclusão de veia central da retina (OVCR), em tratamento com injeções intravítreas de triamcinolona (IVTA) ou bevacizumab (IVB). Métodos: Neste estudo prospectivo, randomizado, duplo mascarado e sham controlado, 35 pacientes com edema macular secundário a OVCR foram randomizados para IVB, IVTA ou para o grupo controle (sham), durante os 6 primeiros meses do estudo. O desfecho primário foi a taxa de incidência de NSA no mês 6. Os desfechos secundários foram alterações médias da acuidade visual corrigida (BCVA) e espessura foveal central (EFC) ao exame de tomografia de coerência óptica, até o mês 12. Resultados: NSA ocorreu em oito (22,86%) olhos, cinco (62,50%) olhos no grupo sham e três (37,50%) olhos no grupo tratado com injeções intravítreas de Triamcinolona, Não houve nenhum caso com NSA no grupo tratado com bevacizumab durante 12 meses de acompanhamento (p=0,009). A BCVA apresentou diferença estatisticamente significante (p<0,05) entre os grupos, somente no mês 1. A EFC não apresentou diferenças estatisticamente significantes (p<0,05) entre os grupos ao longo dos 12 meses. GNV ocorreu em um olho apesar do tratamento com laser e este paciente necessitou de intervenção cirúrgica. Conclusão: O tratamento precoce com injeções intravítreas de Anti VEGF podem diminuir as taxas de neovascularização do segmento anterior e glaucoma neovascular após oclusão de veia central da retina.

Effects of hyaluronic acid on bleeding following third molar extraction

Abstract Objective To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Methods Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. Results HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Conclusions Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.

Management Strategies for Liver Fibrosis

Abstract: Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.