Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum

We evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (IO) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT+IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT+IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.

Seedling survival of Handroanthus impetiginosus (Mart ex DC) Mattos in a semi-arid environment through modified germination speed and post-germination desiccation tolerance / Sobrevivência de plântulas de Handroanthus impetiginosus (Mart ex DC) Mattos em ambiente semi-árido ocorre por modificação da velocidade de germinação e da tolerância à dessecação pós germinação

Abstract Uniform rapid seed germination generally forms a great risk for the plant population if subsequent intermittent precipitation causes desiccation and seedling death. Handroanthus impetiginosus can be found commonly in a wide range of biomes within Brazil including those that are semi-arid. Germination and early growth was studied to understand how germinated seeds survive under these stringent conditions. Accessions were sampled from four seasonally dry biomes in Brazil. Precipitation at the start of the rainy season in the Caatinga, a semi-arid biome, is less predictable and the number of successive dry days per dry interval in the first four months of the rainy season was higher than in the other studied biomes. Plants from the Caatinga produced thicker seeds and this trait concurred with slow germination and stronger osmotic inhibition of germination across the accessions, forming a stress avoidance mechanism in the Caatinga. Post-germination desiccation tolerance was high in the Caatinga accession, could be re-induced in accessions from biomes with more regular precipitation (Cerrado and transition zone), but remained poor in the Cerradão accession; thus forming a stress tolerance mechanism. Production of adventitious roots ascertained survival of all tested individuals from all four locations, even if protruded radicles did not survive desiccation, forming an additional stress tolerance mechanism. A sequence of stress avoidance and stress tolerance mechanisms in seeds and germinated seeds was associated with precipitation patterns in different biomes. These mechanisms purportedly allow rapid seedling establishment when conditions are suitable and enable survival of the young seedling when conditions are adverse.

Resumo A germinação rápida e uniforme geralmente pode apresentar riscos para a população de plantas caso a precipitação ocorra de maneira intermitente, provocando seca e morte das plântulas. Handroanthus impetiginosus pode ser encontrado em uma grande variedade de biomas no Brasil. A germinação e o crescimento inicial das plântulas de Handroanthus impetiginosus foram estudadas para compreender como as sementes germinadas sobrevivem nestas condições. Acessos de quatro biomas que apresentam secas sazonais foram amostrados. A precipitação, no início da estação chuvosa na Caatinga, um bioma semi-árido, é menos previsível e o número de dias secos consecutivos por intervalo de seca, nos primeiros quatro meses da estação chuvosa, foi maior do que nos outros biomas estudados. Plantas do bioma Caatinga produzem sementes mais espessas e essa característica está associada com uma germinação lenta e com a inibição osmótica maior da germinação através dos acessos, formando um mecanismo para evitar o estresse. Tolerância à dessecação em sementes germinadas foi superior no bioma Caatinga e que podem ser reinduzida em acesso com uma precipitação mais regular (Cerrado e na zona de transição), mas manteve-se baixa no acesso Cerradão, formando assim um mecanismo para evitar o estresse. Produção de raízes adventícias foi observada nos indivíduos estudados de todos os quatro biomas, mesmo quando as raízes primárias não sobreviveram à dessecação, formando um mecanismo adicional de tolerância ao estresse. Assim, foi observado estratégias para evitar o estresse e mecanismos de tolerância ao estresse em sementes e sementes germinadas associada com padrões de precipitação nos diferentes biomas estudados. Estes mecanismos podem favorecer o estabelecimento das plântulas de forma rápida quando as condições são adequadas e permitirem a sobrevivência de plântulas quando as condições são adversas.

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Armazenamento de sementes de Alfavaca-cravo (Ocimum gratissimum L. ) / Storage of Clove Basil (Ocimum gratissimum L. ) seeds

A espécie Ocimum gratissimum L. é um subarbusto aromático, pertencente à família Lamiaceae, considerado como importante produtor de óleo essencial e largamente utilizado na medicina popular. Devido à escassez de informações sobre a conservação das sementes dessa espécie o presente estudo objetivou analisar a longevidade das sementes submetidas a diferentes condições de armazenamento, por 12 meses, através de avaliações do potencial germinativo e da capacidade de formação de plântulas normais. As sementes foram armazenadas em três tipos de embalagens: sacos de papel, sacos de papel aluminizado, e frascos de vidro, e nas seguintes condições ambientais: balcão de laboratório, geladeira, e câmara fria. Aos 6, 8, 10 e 12 meses de armazenamento foram avaliados os seguintes parâmetros: umidade, porcentagem de germinação, índice de velocidade de germinação e porcentagem de plântulas normais. Durante o período de armazenamento a manutenção da umidade nas sementes foi mantida, bem como a porcentagem de germinação e de plântulas normais em todos os tratamentos avaliados. As sementes armazenadas apresentaram maiores valores de IVG quando comparadas com as recém-colhidas.

The Ocimum gratissimum L. species is an aromatic subshrub that belongs to the Lamiaceae family and is considered as an important producer of essential oil, widely used in folk medicine. Because of the lack of information about the conservation of O. gratissimum seeds, we aimed to evaluate the longevity of the seeds on different storage conditions for 12 months through the germination and seedling formation percentage in this study. The seeds were stored in three types of packages: paper bags (permeable), aluminized paper bags (semipermeable) and glass flasks (impermeable), in the settings of laboratory bench, refrigerator and cold room over the 12 month period. The germination tests were performed on the 6th, 8th, 10th and 12th month, when moisture, germinability, germination velocity index and percentage of normal seedlings were evaluated. During the storage period, moisture, germinability and percentage of normal seedling were kept in each storage condition. The stored seeds showed increased values of GSI compared to the newly- harvested ones.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

A review of the ticks (Acari, Ixodida) of Brazil, their hosts and geographic distribution - 1. The State of Rio Grande do Sul, Southern Brazil

A review of the ticks (Acari, Ixodida) of the State of Rio Grande do Sul, southern Brazil, was completed as a step towards a definitive list (currently indicated as 12) of such species, their hosts and distribution. The ticks: Argas miniatus (poultry), Ixodes loricatus (opossums), Amblyomma aureolatum (dogs), A. calcaratum (anteaters), A. cooperi (capybaras), A. nodosum (anteaters), A. tigrinum (dogs) (Neotropical) and Rhipicephalus sanguineus (dogs) (introduced, cosmopolitan, Afrotropical) were confirmed as present, in addition to the predominant, Boophilus microplus (cattle) (introduced, pan-tropical, Oriental). Of the further 18 species thus far reported in the literature as present in the state, but unavailable for examination: only Ornithodoros brasiliensis (humans and their habitations) (Neotropical), Ixodes affinis (deer) (Nearctic/Neotropical) and I. auritulus (birds) (Nearctic/Neotropical/Afrotropical/ Australasian) are considered likely; 13 species would benefit from corroborative local data but the majority appear unlikely; reports of A. maculatum (Nearctic/Neotropical, but circum-Caribbean) are considered erroneous; the validity of A. fuscum is in doubt. The very recent, first known report of the tropical Anocentor nitens (horses)(Nearctic/Neotropical), but still apparent absence of the tropical A. cajennense (catholic) (Nearctic/Neotropical) and the sub-tropical/temperate Ixodes pararicinus (cattle) (Neotropical) in Rio Grande do Sul are important for considerations on their current biogeographical distribution and its dynamics in South America. The state has relatively long established, introduced ("exotic"), Old World tick species (B. microplus, R. sanguineus) that continue to represent significant pests and disease vectors to their traditional, introduced domestic animal hosts, cattle and urban dogs. There are also indigenous, New World ticks (A. miniatus, O. brasiliensis, A. aureolatum, A. nitens), as both long established and possibly newly locally introduced species in the state, that should be considered as potential and emergent pests and pathogen vectors to humans and their more recently acquired, introduced domestic animal hosts; rural poultry, dogs and horses.

Tratamento medicamentoso da doença arterial coronária estável em centros de atendimento primário e terciário / Clinical therapheutics for stable coronary artery disease. Differences between primary and tertiary medical care centers

OBJETIVO - Observar a distribuição das drogas em pacientes com doença arterial coronária (DAC) estável, em centros de atendimento (CA) primário e terciário. MÉTODOS - Foram analisados, 300 pacientes, consecutivos, no ambulatório do Grupo de Coronariopatias do INCOR com diagnóstico de DAC, idades entre 31 a 80 (58,5ñ8,0) anos, sendo 205 (68 por cento) do sexo masculino e 95 (32 por cento) do feminino e estudadas as características clínicas e hemodinâmicas. Avaliaram-se as drogas utilizadas, inicialmente, nos CA primários (comunitários) e, posteriormente, no CA terciário. RESULTADOS - As drogas mais utilizadas nos CA primários foram os ß-bloqueadores (50 por cento dos pacientes), nitratos (48 por cento), bloqueadores dos canais de cálcio (46 por cento), ácido acetil-salicílico (44 por cento), diuréticos (30 por cento) e os inibidores da enzima de conversão de angiotensina (ECA), em 11 'por cento' dos pacientes. No CA terciário as drogas mais utilizadas foram o ácido acetil-salicílico (76 por cento dos casos), nitratos (55 por cento), diuréticos (49 por cento), inibidores da ECA (42 por cento), os antagonistas dos canais de cálcio (37 por cento ) e os betabloqueadores (35 por cento dos pacientes). Os ß-bloqueadores foram mais prescritos em CA primário, p=0,02, já os inibidores da ECA, p<0,0001, o ácido acetil-salicílico, p<0,0001 e os diuréticos, p=0,002, foram mais prescritos no CA terciário. CONCLUSÄO - O tratamento farmacológico preconizado para a DAC estável deve ser otimizado em ambos os CA, dando prioridade às drogas que modificam a história natural da doença, como os betabloqueadores, antiagregantes plaquetários, e os inibidores da ECA nos pacientes com disfunção ventricular esquerda.

Alterações eletrocardiográficas durante arteriografia coronária / Electrocardiographic changes during coronary arteriography

Foram estudadas as alteracoes eletrocardiograficas durante arteriografia coronaria seletiva em 30 pacientes, com diagnostico de insuficiencia coronaria. Dezoito deles apresentavam lesoes obstrutivas deles apresentavam lesoes obstrutivas coronarias, 6 alteracoes consideradas nao obstrutivas e outros 6 arterias normais. O contraste usado foi o hypaque M a 75% e, em 4 pacientes, utilizou-se tambem solucao salina a 0,9%. As alteracoes eletricas significativas (p < 0,05) durante injecoes de contraste, tanto na coronaria esquerda (CE) quanto na direita (CD), foram: bradicardia sinusal, aumento da magnitude da onda R, infradesnivelamento dos pontos J e Y do segmento ST, variacoes morfologicas da onda T e prolongamento do intervalo QTc. Observou-se diminuicao da amplitude da onda P apenas durante opacificacao da CD. Em 70% dos pacientes observou-se desvio do AQRS a esquerda, durante injecao em CE, e a direita, durante injecao em CD.Verificou-se desvio do AT a direita durante injecao em CE, em 70% dos pacientes e a esquerda, durante injecao em CD em 90% deles. Com solucao salina, as alteracoes foram semelhantes as do contraste, embora com menor intensidade. Nao houve diferenca (p > 0,05) nas modificacoes observadas nos grupos com e sem insuficiencia coronaria obstrutiva. As alteracoes eletrocardiograficas encontradas foram relacionadas fundamentalmente a alteracoes reflexas neurogenicas e a efeito toxico da solucao injetada