In vitro anticancer and antifungal properties of the essential oil from the leaves of Lippia origanoides kunth.

The essential oil from Lippia origanoides (EOLO) is employed in traditional medicine as it has both antimicrobial and anti-inflammatory properties. The current investigation first evaluated the EOLO's cytotoxic activity in tumour (SiHa and HT-29) and non-tumour (human lymphocyte) cells by MTT. The effect on ROS production was further evaluated in cancer cells by fluorimetry. The oil's mutagenic and antifungal activities were also evaluated using, respectively, the in vitro micronucleus test and the broth microdilution method. The EOLO displayed significant cytotoxicity in both cancer cell lines, with IC50 values of 20.2 µg/mL and 24.3 µg/mL for HT-29 and for SiHa cell lines, respectively. EOLO increased ROS production, was unable to raise the micronucleus frequencies and significantly reduced the cytokinesis block proliferation indices, revealing its anti-proliferative action. The results demonstrate that EOLO is devoid of mutagenic activity but possesses significant activity against tumour and non-tumour human cells, reinforcing its biological potential.

Integrated Approach Including Docking, MD Simulations, and Network Analysis Highlights the Action Mechanism of the Cardiac hERG Activator RPR260243.

hERG is a voltage-gated potassium channel involved in the heart contraction whose defections are associated with the cardiac arrhythmia Long QT Syndrome type 2. The activator RPR260243 (RPR) represents a possible candidate to pharmacologically treat LQTS2 because it enhances the opening of the channel. However, the molecular detail of its action mechanism remains quite elusive. Here, we address the problem using a combination of docking, molecular dynamics simulations, and network analysis. We show that the drug preferably binds at the interface between the voltage sensor and the pore, enhancing the canonical activation path and determining a whole-structure rearrangement of the channel that slightly impairs inactivation.

Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

Biomineralization of Nickel Struvite Linked to Metal Resistance in Streptomyces mirabilis.

Biomineral formation is a common trait and prominent for soil Actinobacteria, including the genus Streptomyces. We investigated the formation of nickel-containing biominerals in the presence of a heavy-metal-resistant Streptomyces mirabilis P16B-1. Biomineralization was found to occur both in solid and liquid media. Minerals were identified with Raman spectroscopy and TEM-EDX to be either Mg-containing struvite produced in media containing no nickel, or Ni-struvite where Ni replaces the Mg when nickel was present in sufficient concentrations in the media. The precipitation of Ni-struvite reduced the concentration of nickel available in the medium. Therefore, Ni-struvite precipitation is an efficient mechanism for tolerance to nickel. We discuss the contribution of a plasmid-encoded nickel efflux transporter in aiding biomineralization. In the elevated local concentrations of Ni surrounding the cells carrying this plasmid, more biominerals occurred supporting this point of view. The biominerals formed have been quantified, showing that the conditions of growth do influence mineralization. This control is also visible in differences observed to biosynthetically synthesized Ni-struvites, including the use of sterile-filtered culture supernatant. The use of the wildtype S. mirabilis P16B-1 and its plasmid-free derivative, as well as a metal-sensitive recipient, S. lividans, and the same transformed with the plasmid, allowed us to access genetic factors involved in this partial control of biomineral formation.

Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel.

The elusive activation/deactivation mechanism of hERG is investigated, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including the Long QT Syndrome. Firstly, the available structural data are integrated by providing a homology model for the closed state of the channel. Secondly, molecular dynamics combined with a network analysis revealed two distinct pathways coupling the voltage sensor domain with the pore domain. Interestingly, some LQTS-related mutations known to impair the activation/deactivation mechanism are distributed along the identified pathways, which thus suggests a microscopic interpretation of their role. Split channels simulations clarify a surprising feature of this channel, which is still able to gate when a cut is introduced between the voltage sensor domain and the neighboring helix S5. In summary, the presented results suggest possible activation/deactivation mechanisms of non-domain-swapped potassium channels that may aid in biomedical applications.

Hypofractionated radiotherapy recommendations for localized prostate cancer in Brasil.

OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.

Hypofractionated radiotherapy recommendations for localized prostate cancer in Brasil

SUMMARY OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.

Adenosinergic signalling in chondrogenesis and cartilage homeostasis: Friend or foe?

Chondrocytes and their mesenchymal cell progenitors secrete a variety of bioactive molecules, including adenine nucleotides and nucleosides, but these molecules are not usually highlighted in review papers about the secretome of these cells. Ageing and inflammatory insults compromise chondrocytes ability to keep ATP/adenosine synthesis, release and turnover. Cartilage homeostasis depends on extracellular adenosine levels, which acting via four P1 purinoceptor subtypes modulates the release of pro-inflammatory mediators, including NO, PGE2 and several cytokines. Native articular cartilage is challenged by synovial fluid flow during normal joint motion transiently increasing ATP release and adenosine formation in the joint microenvironment. Excessive joint motion and shockwave trauma are deleterious to cartilage homeostasis due to HIF-1α overexpression, resulting in disproportionate ecto-5'-nucleotidase/CD73 production, adenosine accumulation and superfluous A2B receptors activation. Scarcity of data however exists on the putative interplay between coexistent high affinity (A2A and A3) and low affinity (A2B) adenosine receptors activation affecting stem cells fate towards preferential chondrogenic or osteogenic lineages in the human cartilage. Hints gathered in this commentary result mainly from studies using human immortalized cell lines and animal (e.g. rodent, equine, bovine) tissue samples. The available data point towards adenosine A2A and A3 receptors having cartilage protective roles, while excessive adenosine accumulation may be detrimental via low affinity A2B receptors activation, with little reference to the putative role of the adenosine forming enzyme ecto-5'-nucleotidase/CD73. Thus, emphasizing the multiple pathways responsible for controlling adenosine signalling in cartilage will certainly impact on the search for novel therapeutic targets for highly disabling articular disorders.

Neurological signs described at the Federal University of Rio de Janeiro: connecting the past to the future / Sinais neurológicos descritos na Universidade Federal do Rio de Janeiro: conectando o passado ao futuro

ABSTRACT The Federal University of Rio de Janeiro (UFRJ) is one of the pillars of Brazilian Medicine and, in Neurology, has always shown prominence, with notable professors such as Antônio Austregésilo and Deolindo Couto. Historically, practitioners of the UFRJ Medical School have discovered neurological signs that, although used in medical and academic practice, have never been published. Objective Our aim was to bring these signs to the forefront so that they become properly recognized and studied. Methods We conducted our search by questioning 49 professors and physicians by e-mail about neurological signs that they remembered having had contact with at UFRJ. Results We report on the unpublished pillow sign in progressive supranuclear palsy; the Brazilian sandal sign in functional or malingering patients; the dermographism sign in acute meningitis; the reverse forearm rolling sign in functional palsies; the cycling maneuver in parkinsonian syndromes and the Sá Cavalcanti sign, a Babinski equivalent. We have also recollected the following published signs for their historical relevance: the Austregésilo sign (Antônio Austregésilo), another Babinski equivalent; the digiti quinti rolling sign in subtle palsies (Péricles Maranhão) and the digiti quinti sign in hemiplegic migraine (Maurice Vincent). These signs are easily reproduced and have potential clinical applicability, deserving to be more thoroughly studied. Conclusions Through a qualitative methodology, we have identified six original unpublished neurological signs known by the academic community, establishing the contribution of these individuals to the expansion of neurological semiology.

RESUMO A Universidade Federal do Rio de Janeiro é um dos pilares da Medicina brasileira. Na Neurologia sempre se destacou com notáveis professores, como Antônio Austregésilo e Deolindo Couto. Historicamente, professores da Faculdade de Medicina da UFRJ descreveram sinais neurológicos que, embora utilizados na prática médica e acadêmica, nunca foram publicados. Objetivo Fazer ressurgir sinais clínicos neurológicos nunca antes publicados, para que possam ser devidamente reconhecidos e estudados. Métodos Quarenta e nove professores e médicos foram contactados por e-mail. Dez responderam questionário semi-estruturado acerca de sinais neurológicos conhecidos pelos profissionais, porém nunca publicados. Resultados Foram relatados: 1- Sinal do Travesseiro - na Paralisia Supranuclear Progressiva; 2- Sinal da sandália- nos pacientes funcionais ou simuladores; 3- Sinal do dermografismo- nas meningites agudas da infância; 4- Sinal do rolamento reverso do antebraço- nas paralisias funcionais; 5- Manobra do pedalar- nas síndromes parkinsonianas; 6- Sinal de Sá Cavalcanti- um sucedâneo de Babinski. Revisamos também os seguintes sinais publicados, por sua relevância histórica: o sinal Austregésilo, outro sucedâneo de Babinski; sinal do rolamento do quinto dedo- nas paralisias sutis e o sinal do quinto dedo- na enxaqueca hemiplégia. Conclusão Por meio de metodologia qualitativa, identificamos seis sinais neurológicos inéditos originais. Esses sinais são de fácil reprodutibilidade e têm aplicabilidade clínica potencial, merecendo estudos adicionais.

Assessing nickel tolerance of bacteria isolated from serpentine soils.

Serpentine soils present unique characteristics such as a low Ca/Mg ratio, low concentration of nutrients, and a high concentration of heavy metals, especially nickel. Soil bacterial isolates from an ultramafic complex located in the tropical savanna known as the Brazilian Cerrado were studied. Nickel-tolerant bacteria were obtained, and their ability to remove nickel from a culture medium was assessed. Bacterial isolates presented higher tolerance to nickel salts than previously reported for bacteria obtained from serpentine environments in other regions of the world. In addition, the quantification of nickel in cell pellets indicated that at least four isolates may adsorb soluble forms of nickel. It is expected that information gathered in this study will support future efforts to exploit serpentine soil bacteria for biotechnological processes involving nickel decontamination from environmental samples.

Toxina botulínica para tratamento da sialorreia nos pacientes com doença de Parkinson / Botulinum toxin for treatment of sialorrhea in patients with Parkinson's disease

A sialorreia/ptialismo é um sintoma não motor frequente da doença de Parkinson, que pode causar impacto na saúde e na qualidade de vida dos pacientes. O sintoma decorre da combinação da disfagia com disautonomia e, muitas vezes, também do efeito adverso de drogas frequentemente utilizadas no tratamento de sintomas da doença, como por exemplo, os antipsicóticos atípicos e os inibidores da acetilcolinesterase. Diversas opções terapêuticas são utilizadas na prática clínica para controle da sialorreia, dentre elas, drogas anticolinérgicas ou antagonistas dos receptores adrenérgicos, injeção de toxina botulínica, cirurgia, radioterapia e terapias comportamentais e fonoaudiológicas. Este trabalho faz uma revisão das propostas terapêuticas até o presente momento para controlar a secreção de saliva dos pacientes com doença de Parkinson. A injeção de toxina botulínica nas glândulas salivares guiada por ultrassom é a opção com mais evidência de eficácia e segurança, de acordo com os últimos estudos.

Sialorrhea is a frequent nonmotor symptom in Parkinson´s disease (PD) that influences the patients' health and quality of life. The symptom arises from a combination of difficulty in swallowing saliva, autonomic dysfunction or as a side effect of frequent used drugs to control symptoms of the disease, as for example, atypical antipsychotics and acetylcholinesterase inhibitors. In clinical practice, different therapeutic approaches are used to control sialorrhea, such as anticholinergic or beta adrenergic antagonistic drugs, botulinum toxin injection, surgery, radiotherapy, behavioral psychotherapy and speech therapy. This paper reviews the therapeutic options available until now to control the loss of saliva from PD patient. Botulinum toxin injection in the salivary glands guided by ultrasound shows the best efficacy and security profile, according to the last published data.

Effect of Ocimum gratissimum in Mouthrinses on De Novo Plaque Formation. A Randomized Clinical Trial

Resumo O objetivo do presente estudo foi avaliar clinicamente em humanos o efeito antiplaca de Ocimum gratissimum (Og). Quinze adultos saudáveis participaram deste estudo cruzado, duplo-cego, por meio de um modelo de acúmulo de placa parcial de 3 dias. Os voluntários aboliram qualquer método mecânico de higiene oral e foram inicialmente designados para usar os seguintes enxaguatórios bucais: água destilada (solução AD), digluconato de clorexidina a 0,12% (solução CLX) ou 10% Og (solução Og). O índice de placa (IPL) foi registrado em todos os dentes inferiores no final do experimento e os testes estatísticos Kruskal-Wallis (α=0,05) e Mann-Whitney (α=0,05) foram utilizados para estimar a diferença entre os grupos. Os resultados clínicos demonstraram diferença estatisticamente significante entre os três grupos (p<0,05), favorecendo os grupos CLX e Og; entretanto o grupo CLX foi mais efetivo que o grupo Og (p<0,05). Os enxaguatórios bucais contendo digluconato de clorexidina e Og a 10% foram capazes de reduzir a formação de nova placa bacteriana, mas Og mostrou resultados mais limitados em comparação ao digluconato de clorexidina.

Abstract The aim of this study was to evaluate the antiplaque effect of Ocimum gratissimum (Og) by in vivo investigation. Fifteen healthy volunteers participated in a crossover, double-blind clinical study, using a 3-day partial-mouth plaque accumulation model. The participants abolished any method of mechanical oral hygiene and they were randomly assigned to initially use just the following mouthrinses: distilled water (DW solution), 0.12% chlorhexidine digluconate (CLX solution) or 10% Og (Og solution). The plaque index (PLI) was recorded in all mandibular teeth at the end of the trial and the Kruskal-Wallis (α=0.05) and Mann-Whitney (α=0.05) tests were used to estimate the difference among groups. The clinical results showed statistically significant difference among the groups (p<0.05), favoring the CLX solution and Og solution, but the first was more effective (p<0.05). The mouthrinses containing 0.12% chlorhexidine digluconate and 10% Og were able to inhibit plaque re-growth, however Og showed more limited results in comparison to CLX.

Perfil de propriedades rurais com pastos invadidos por Pteridium arachnoideum na região norte de Mato Grosso e prevalência de hematúria enzoótica bovina / Profile of farms with pastures invaded by Pteridium arachnoideum in northern Mato Grosso and prevalence of bovine enzootic hematuria

Descreve-se o perfil de 40 propriedades rurais com pastagens invadidas por Pteridium arachnoideum na região norte de Mato Grosso, bem como a prevalência de hematúria enzoótica bovina (HEB) em bovinos de leite e corte nessa região. A HEB foi observada em 15/40 propriedades com prevalências variando entre 0,8 e 16,6%. Aspectos relacionados à implantação das pastagens e manejos utilizados foram discutidos. A maior parte das propriedades que apresentaram HEB possuíam pastagens altamente invadidas pela planta, enquanto que a maioria das propriedades que nunca apresentaram animais acometidos por HEB possuíam pastos com áreas invadidas abaixo de 10%. O desmatamento e a utilização de queimada foram fatores determinantes na invasão de piquetes por P. arachnoidem...

The profile of 40 farms with pastures invaded by Pteridium arachnoideum in northern Mato Grosso as well as the prevalence of bovine enzootic haematuria (BEH) in dairy and beef cattle in the region are described. The BEH was observed in 15/40 properties with prevalence rates ranging from 0.8 to 16.6%. Aspects related to the deployment of pastures and management are discussed. In most farms where BEH occurs, the pastures were highly invaded by the plant, whereas in most farms where HEB does not occur the pastures had less than 10% of Pteridium arachnoideum. Deforestation and the use of fire were determinant factors in the invasion of the paddocks by P. arachnoideum...

Avaliação do efeito do extrato da casca do cajueiro sobre microrganismos de biofilme subgengival. Estudo experimental in vitro / Evaluation of the activity of Anacardium occidentale on microorganisms of subgingival biofilm: experimental study in vitro

O objetivo deste estudo foi avaliar o efeito do extrato hidroalcoólico da casca do cajueiro (AO) sobre amostras microbiológicas de biofilme subgengival. Estas foram coletadas de bolsa periodontal, colocadas em meio de cultura líquido BHI pré-reduzido (Brain Heart Infusion) e triplicadas em placas de ágar-sangue contendo discos imersos em diferentes concentrações do extrato hidroalcoólico da casca do cajueiro (12,5% e 50%), em solução de digluconato de clorexidina a 0,12% e em solução salina a 0,9%. Independente da concentração utilizada, o AO não apresentou efeito sobre o crescimento bacteriano, de forma semelhante à solução salina e diferente da solução de digluconato de clorexidina a 0,12%, que demonstrou um halo de inibição de 11 mm. Assim, o extrato hidroalcoólico da casca do cajueiro não exerceu efeito inibitório in vitro sobre amostras microbiológicas de biofilme subgengival.

The aim of this study was to evaluate the effect of the Anacardium occidentale (AO) hydroalcoholic extract on oral microorganisms from subgingival biofilm. They were immerged in a pre-reduced BHI (Brain Heart Infusion) and distributed in plates containing agar-sanguis in contact with various solutions: 0.9% saline; 0.12% chlorhexidine digluconate; 12.5% and 50% AO. The saline solution had no effect on bacterial growth in a similar manner than AO, independently of its concentration. 0.12% chlorhexidine digluconate showed an expressive inhibition hale (11mm). Then, AO did not show inhibitory effect in vitro on microorganisms from subgingival biofilm

Avaliação dos extratos de anacardium occidentale linn e lippia sidoides cham no processo de cicatrização tecidual. Estudo histológico em dorso de ratos / Evaluation of extracts from Anacardium occidentale Linn. and Lippia sidoides Cham. on wound healing process. Histological study in rats

O objetivo deste trabalho foi avaliar histologicamente o efeito dos géis contendo extratos de Anacardium occidentale Linn. (AO) e Lippia sidoides Cham.(LS) no reparo tecidual de feridas cutâneas em dorso de ratos. Dezoito ratos da raça Wistar foram divididos aleatoriamente em três grupos de seis animais cada, de acordo com o período experimental: Grupo 1 (n = 6), sacrificados no 1º dia; Grupo 2 (n = 6), sacrificados no 7º dia e grupo 3 (n = 6), sacrificados no 10º dia. Quatro feridas cutâneas foram realizadas por meio de escarificação utilizando bisturi com lâmina nº 10 no dorso dos animais e sobre elas foram aplicadas topicamente em dose única diária, uma das quatro substâncias. Estabeleceu-se o seguinte protocolo: grupo A (perfuração superior, lado esquerdo) – gel placebo (Carbopol); grupo B (perfuração inferior, lado esquerdo) – gel de digluconato de clorexidina a 2%; grupo C (perfuração superior, lado direito) – gel de AO a 10%; grupo D (perfuração inferior, lado direito) – gel de LS a 10%. Não houve diferença qualitativa e quantitativa no processo de cicatrização entre os grupos nos dias 1 e 10 (p>0,05), porém aos 7 dias os géis contendo os fitoterápicos mostraram resultados mais favoráveis (p<0,05), apresentando uma cicatrização mais rápida neste período

The aim of this study was to evaluate, by histological analysis, the effect of gels containing extracts of Anacardium occidentale Linn and Lippia sidoides Cham on wound healing in Wistar rats. Eighteen rats were randomly divided into three groups with six animals each: Group 1 (n = 6) sacrificed on 1st day, Group 2 (n = 6) sacrificed on 7th day and group 3 (n = 6) sacrificed on 10th day. Four wounds were made by scraping using a scalpel blade #10 on the dorsum of the animals, and one of the four substances applied once a day, following the protocol: group A (upper wound, left side) – placebo gel (Carbopol); group B (bottom wound, left side) – 2% chlorhexidine digluconate gel; group C (upper wound, right side) – 10% Anacardium occidentale Linn gel; group D (bottom wound, right side) – 10% Lippia sidoides Cham gel. There were no qualitative and quantitative differences in the healing process among groups on days 1 and 10 (p>0.05), but on day 7 the herbal gels showed more favorable results (p<0.05), improving the wound healing in this period