DEVELOPMENT AND VALIDATION OF A HPLC METHOD FOR QUANTIFICATION OF URSOLIC ACID IN SOLID DISPERSIONS

DEVELOPMENT AND VALIDATION OF A HPLC METHOD FOR QUANTIFICATION OF URSOLIC ACID IN SOLID DISPERSIONS. Ursolic acid is a natural molecule that presents several pharmacological properties. In this work, an analytical method by RP-HPLC has been developed and validated for quantification of this drug in the solid dispersions, using PEG 6000 and Poloxamer 407 as polymers. The method was specific, linear in the range of 1.0-50.0 mu g mL(-1) (r<0.99), precise (CV < 5% for both inter-and intra-assays), accurate (maximum deviation of +/- 13%), and robust to the parameters evaluated. This method has proved to be simple and useful for ursolic acid determination in solid dispersions, enabling its determination in pharmaceutical dosage form.

Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment

BACKGROUND One aspect of a multidimensional approach to understanding asthma as a complex dynamic disease is to study how lung function varies with time. Variability measures of lung function have been shown to predict response to beta(2)-agonist treatment. An investigation was conducted to determine whether mean, coefficient of variation (CV) or autocorrelation, a measure of short-term memory, of peak expiratory flow (PEF) could predict loss of asthma control following withdrawal of regular inhaled corticosteroid (ICS) treatment, using data from a previous study. METHODS 87 adult patients with mild to moderate asthma who had been taking ICS at a constant dose for at least 6 months were monitored for 2-4 weeks. ICS was then withdrawn and monitoring continued until loss of control occurred as per predefined criteria. Twice-daily PEF was recorded during monitoring. Associations between loss of control and mean, CV and autocorrelation of morning PEF within 2 weeks pre- and post-ICS withdrawal were assessed using Cox regression analysis. Predictive utility was assessed using receiver operator characteristics. RESULTS 53 out of 87 patients had sufficient PEF data over the required analysis period. The mean (389 vs 370 l/min, p<0.0001) and CV (4.5% vs 5.6%, p=0.007) but not autocorrelation of PEF changed significantly from prewithdrawal to postwithdrawal in subjects who subsequently lost control, and were unaltered in those who did not. These changes were related to time to loss of control. CV was the most consistent predictor, with similar sensitivity and sensitivity to exhaled nitric oxide. CONCLUSION A simple, easy to obtain variability measure of daily lung function such as the CV may predict loss of asthma control within the first 2 weeks of ICS withdrawal.

Deadspace estimation from CO2 versus molar mass measurements in infants

BACKGROUND: Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. METHODS: Breath-by-breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. RESULTS: Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra-measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. CONCLUSIONS: Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants.

In vitro-activity of oily calcium hydroxide suspension on microorganisms as well as on human alveolar osteoblasts and periodontal ligament fibroblasts.

BACKGROUND Findings from animal and human studies have indicated that an oily calcium hydroxide suspension (OCHS) may improve early wound healing in the treatment of periodontitis. Calcium hydroxide as the main component is well known for its antimicrobial activity, however at present the effect of OCHS on the influence of periodontal wound healing/regeneration is still very limited. The purpose of this in vitro study was to investigate the effect of OCHS on periodontopathogenic bacteria as well as on the attachment and proliferation of osteoblasts and periodontal ligament fibroblasts. METHODS Human alveolar osteoblasts (HAO) and periodontal ligament (PDL) fibroblasts were cultured on 3 concentrations of OCHS (2.5, 5 and 7.5 mg). Adhesion and proliferation were counted up to 48 h and mineralization was assayed after 1 and 2 weeks. Furthermore potential growth inhibitory activity on microorganisms associated with periodontal disease (e.g. Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans) as well as the influence of periodontopathogens and OCHS on the HAO and PDL fibroblasts counts were determined. RESULTS More than a 2-fold increase in adherent HAO cells was observed at 4 h following application of OCHS when compared to the control group (p = 0.007 for 2.5 mg). Proliferation of HAO cells at 48 h was stimulated by moderate concentrations (2.5 mg; 5 mg) of OCHS (each p < 0.001), whereas a high concentration (7.5 mg) of OCHS was inhibitory (p = 0.009). Mineralization was observed only for HAO cells treated with OCHS. OCHS did not exert any positive effect on attachment or proliferation of PDL fibroblasts. Although OCHS did not have an antibacterial effect, it did positively influence attachment and proliferation of HAO cells and PDL fibroblasts in the presence of periodontopathogens. CONCLUSIONS The present data suggests that OCHS promotes osteoblast attachment, proliferation and mineralization in a concentration-dependent manner and results are maintained in the presence of periodontal pathogens.

Allers illustrerade konversationslexikon : praktisk uppslagsbok i det allmänna vetandets olika grenar.

1. bd. A-C -- 2. bd. D-F -- 3. bd. G-J -- 4. bd. K-Mg -- 5. bd. Mi-P -- 6. bd. Q-S -- 7. bd. T-Ö : med supplement.

Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI (R)) - A short report

We observed unexpected high plasma concentrations of tobrarriycin (48.5 and 28.1 mg/L) in fingerprick blood samples after the nebulization of tobramycin solution for inhalation (tobramycin 300 mg/5 mL, TOBI(R)) by 2 young children aged 3 years. To investigate whether dermal contamination could be the source of error, 3 adult volunteers were present during another nebulization by a third child (age 2 years). The volunteers had exposure to tobramycin by handling the nebulizer or the nebule and also by inhalation from holding the child and being in close proximity while TOBI(R) was being administered. Five blood samples by fingerprick and 2 by venipuncture were collected and assayed for tobramycin concentration. On each occasion the site was swabbed with alcohol wipes to mimic standard patient sampling methods. One site was resampled after cleaning of hands with 2% chlorhexidine gluconate and water. Tobramycin concentrations from venipuncture 1-2 hours after nebulization were all < 0.2 mg/L except for 1 result of 1.2 mg/L. The tobramycin concentrations from fingerpricks before hand washing varied between 6.8 and 172 mg/L, and after hand washing between 0.3 and 17.6 mg/L. Contamination of fingers with tobramycin is likely to have caused the error in the 2 initial cases and did cause misleadingly elevated levels in the adult volunteers. We caution that therapeutic drug monitoring of nebulized tobramycin should not be done by fingerprick sampling, and care should be taken to avoid contamination of the venipuncture site.

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study

OBJECTIVE Cannabidiol (CBD) and D9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. RESULTS Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = 21.2 mmol/L; P < 0.05) and improved pancreatic b-cell function (HOMA2 b-cell function [ETD = 244.51 points; P < 0.01]), adiponectin (ETD = 25.9 3 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = 26.02 mmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (2898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. CONCLUSIONS THCV could represent a newtherapeutic agent in glycemic control in subjects with type 2 diabetes.

Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy

Background and aims: The selective SGLT2 inhibitor dapagliflozin (DAPA) reduces hyperglycaemia independently of insulin secretion or action by inhibiting renal glucose reabsorption. This study (MB102014) is a randomised double-blind, placebo (PBO)-controlled trial of DAPA added to metformin (MET) in T2DM (n=546) inadequately controlled with MET alone. Previously reported short-term data at week 24 showed significant mean reductions in the primary [HbA1c] and secondary [fasting plasma glucose (FPG) and weight] endpoints with DAPA compared to PBO. Here we report efficacy and safety results at week 102 of the long-term extension. Materials and methods: Patients aged 18-77 years with HbA1c 7-10% received DAPA 2.5 mg, 5 mg, 10 mg or PBO, plus open-label MET (≥1500mg/d). Exploratory endpoints at week 102 included changes from baseline in HbA1c, FPG and weight, and were analyzed by longitudinal repeated measures analysis. Results: Overall 71.2% of patients completed 102 weeks of the study; fewer on PBO (63.5%) than on DAPA 2.5 mg, 5 mg, and 10 mg (68.3%, 73.0%, 79.8%), due mainly to more patients on PBO discontinuing for lack of efficacy. At week 102, all DAPA groups showed greater mean reductions from baseline in HbA1c, FPG and weight compared to PBO (table), effects that were similar to those observed at week 24 and maintained throughout the trial. More patients at week 102 also achieved a therapeutic response of HbA1c<7% with DAPA 2.5 mg, 5 mg, and 10 mg (20.7%, 26.4%, 31.5%) than with PBO (15.4%). Adverse events (AEs), serious AEs and AEs leading to discontinuation were balanced across all groups. Signs and symptoms suggestive of genital infection (GenInf) were reported in 11.7%, 14.6%, 12.6% (DAPA 2.5 mg, 5 mg, 10 mg) and 5.1% (PBO) of patients, with 1 discontinuation due to GenInf. Signs and symptoms suggestive of urinary tract infection (UTI) were reported in 8.0%, 8.8%, 13.3% (DAPA 2.5 mg, 5 mg, 10 mg) and 8.0% (PBO), with 1 discontinuation due to UTI. No event of pyelonephritis was reported. Conclusion: In comparison to PBO, DAPA added to MET over 102 weeks demonstrated greater and sustained improvements in glycaemic control, clinically meaningful reduction in weight, and no increased risk of hypoglycaemia in patients with T2DM inadequately controlled with MET alone.

Comunidades Escolares de Aprendizagem Gulbenkian XXI: exercício metodológico exploratório de análise e estrutura hierárquica de itens e composição sociodemográfica dos perfis de resposta

: No presente artigo, pretendemos, num primeiro momento, evidenciar a importância das práticas colaborativas e participadas na elaboração de instrumentos de avaliação das aprendizagens e da sua aplicação em ambientes virtuais, permitindo, por um lado, acompanhar o desempenho dos alunos em tempo real e, por outro, decorrente da sua transversalidade, induzir processos de autorregulação colaborativa entre professores e microrredes de escolas. A análise da dificuldade e da discriminação dos itens da prova e das suas interações com recurso ao diagrama de dispersão permitiu projetar as características e qualidade das questões da prova diagnóstica, revelando-se a componente de Português com maior equilíbrio na conjugação dificuldade-discriminação. O recurso ao algoritmo Exhaustive CHAID para além de permitir apurar que a pontuação global média obtida pelos 133 alunos que realizaram a prova foi de 68,42% e verificar a existência de alguma heterogeneidade dos resultados (Cv=26,5%), permitiu especialmente evidenciar a estrutura hierárquica das respostas e identificar os fluxos sequenciais em termos de resposta certa ou errada na produção da pontuação global. Por outro lado, a análise das sequências estruturais associadas aos nós de maior contraste conduziu ainda ao destaque de seis nós, organizados em torno dos pares de nós (28, 14), (25,18) e (27,24). O primeiro dos pares (28, 14), é também o par de maior contraste e o nó 28, com maior concentração de respostas certas, o nó com maior peso amostral, representando com os seus 32 casos quase um quarto dos alunos que realizaram a PGD_K3 (24,1%); ao contrário, o nó 14 com apenas 7 casos e representando 5,3% da amostra geral, registou uma pontuação global na prova de 34,2%. Por último, a análise da estrutura composicional dos perfis em torno de algumas variáveis contextuais sociodemográficas foi reveladora de uma estrutura de desempenho académico na prova que parece continuar mais permeável e refém de fatores contextuais exógenos do que propriamente das dinâmicas internas escolares.

Nutrição mineral de plantas ornamentais XII: Deficiências de N, P, Ca, Mg, S e B em crisântemo (Chrysanthemum morifolium cv golden polaris)

Com o objetivo de determinar: Os sintomas de deficiência de macronutrientes e de boro, de modo a relacioná-los com a composição química da planta; Foi conduzido um experimento em casa-de-vegetação com plantas de crisântemo cultivadas em substrato de sílica e irrigadas com soluções nutritivas, submetidas aos tratamentos: completo, omissão e nitrogênio (-N), omissão de fósforo (-P), omissão de potássio (-K), omissão de cálcio (-Ca), omissio de magnésio (-Mg), omissão de enxofre (-S) e omissão de boro (-B). O desenvolvimento dos sintomas foi acompanhado e, ao final do ciclo, as plantas foram colhidas e separadas em folhas novas, folhas velhas, hastes e inflorescências para serem analisadas quanto a concentração dos nutrientes. Os autores concluiram que: A sintomatologia de carência de nutrientes aparece, em sequência, para os elementos N, B, S, K, Ca, P e Mg, sendo mais pronunciada nos tratamentos -N, -K, -B e -Ca. Os níveis de nutrientes nas folhas de plantas sadias, expressos em função da matéria seca, estão na faixa de:N-1,02% -2,25%; P-0,08%-0,13%; K-2,79%-2,87%; Ca -1,18%-1 ,68%; Mg-0,70%-0,93%; S- 0,93%-0,13% e B-56,5 ppm-67,25 ppm. Os níveis de nutrientes nas folhas de plantas com sintomas de carência, expressos na matéria seca, são: N-0,73%; P-0,03%; K-0,42%; Ca-0,46%; Mg-0,48%; S-0,10% e B-33 ppm.

Soluções de manutenção na pós-colheita de Chrysanthemum morifolium cv. Dragon

The development and use of techniques that extend the life vase of the flowers, maintaining the quality of the product, is essential for reducing postharvest losses. The objective of this work was to evaluate different solutions for maintenance, associated or not to sucrose, in maintaining the postharvest quality of chrysanthemum stems. The treatments used distilled water, 8-HQC to 100 mg L-1, 8-HQC to 100 mg L-1 + sucrose 50 g L-1, 8-HQC to 200 mg L-1, 8-HQC to 200 mg L-1 + sucrose 50 g L-1. Physical assessments were made: color, fresh mass and relative water content; chemical evaluations: reducing sugars and pigments, and qualitative assessments: turgidity, color of the flowers, and number of buttons, open flowers and partially open flowers. The combination of 8-HQC 200 mg L-1 + sucrose 50 g L-1 was the best performance that made for maintaining the quality of flower stems, favoring the opening of buttons and turgidity of petals. Sucrose contributed to better maintenance of the reserve substances in the shaft, which had increased the flower vase life.

Eutectic solidification mode in sodium modified Al-7 mass %Si-3.5 mass %Cu-0.2 mass %Mg casting alloys

The influence of sodium (Na) on nucleation and growth of the Al-Si eutectic in a commercial hypoeutectic Al-Si-Cu-Mg foundry alloy has been investigated. The microstructural evolution during eutectic solidification was studied by a quenching technique. By comparing the orientation of the aluminium in the eutectic to that of the surrounding primary aluminium dendrites by EBSD, the eutectic solidification mode could be determined. The results show that the eutectic solidification starts near the mould wall and evolves with front growth opposite the thermal gradient on a macro-scale, and on a micro-scale with independent heterogeneous nucleation of eutectic grains in interdendritic spaces. Na-modified alloys therefore behave significantly differently from those modified by other elemental additions.

Efeitos da aplicação de manganês no crescimento, na nutrição e na produção de matéria seca de plantas de Brachiaria brizantha (cv. MG4) em condições de casa de vegetação

A adubação com micronutrientes, como o manganês em gramíneas forrageiras tropicais, contribui para o atendimento das exigências nutricionais tanto das plantas quanto dos animais. Objetivou-se, neste trabalho, estudar os efeitos da aplicação de manganês no crescimento, na nutrição e na produção de matéria seca de plantas de Brachiaria brizantha, em condições de casa de vegetação. Para isto, realizou-se um experimento em casa de vegetação da FCAV/UNESP, Campus de Jaboticabal, com Brachiaria brizantha (cv. MG4), em vasos com 3,5 dm³ preenchidos com amostras de um Latossolo Vermelho distrófico (Mn = 0,6 mg dm-3). O delineamento experimental foi inteiramente casualizado, com cinco tratamentos, que corresponderam às doses de manganês (0, 15, 30, 60 e 120 mg dm-3), e quatro repetições. Avaliaram-se, nos dois cortes da forrageira (primeiro corte, 35 dias após o transplantio e, segundo, 30 dias após o primeiro), as variáveis de crescimento, produção de massa de forragem, teor e acúmulo de Mn na parte aérea. As doses de manganês aplicadas aumentaram a concentração deste micronutriente no solo e nas plantas e a produção de massa de forragem no primeiro corte. A Brachiaria brizantha cv. MG4 apresenta alta tolerância ao manganês, atingindo elevados teores de Mn na parte aérea, mesmo sem provocar sintomas visuais de toxicidade.

Uso de fitorreguladores no desenvolvimento de frutos na atemoieira (Annona cherimola x A. squamosa cv. Gefner)

Este trabalho foi realizado com atemoieiras 'Gefner', com o objetivo de avaliar o efeito de fitorreguladores no pegamento de frutos. Foram realizados três experimentos, no município de Matias Cardoso, Minas Gerais. No primeiro, avaliaram-se quatro tipos de auxinas: os ácidos indol butírico (AIB), indol acético (AIA), naftaleno acético (ANA) e diclorofenoxiacético (2,4-D), combinados com três concentrações (150, 300 e 450 mg L-1). O ácido giberélico (GA3) também foi aplicado, na dosagem de 1 g L-1, aos 14 e 21 dias após a primeira aplicação das auxinas. No segundo experimento, testaram-se o AIA, AIB e ANA, combinados em duas concentrações (450 e 600 mg L-1). No terceiro experimento, avaliou-se a aplicação do ANA na dose de 450 mg L-1 associado com número de aplicações: semanal até 35 dias; semanal até 70 dias; semanal até 105 dias e a cada duas semanas. O GA3 foi utilizado na dosagem de 1 g L-1, em quatro aplicações, aos 13, 27, 41 e 54 dias após a primeira aplicação do ANA. Em todos os experimentos, a testemunha foram flores polinizadas artificialmente. ANA foi a auxina sintética que propiciou as maiores médias de pegamento dos frutos, com 8% até aos 148 dias após a primeira aplicação. A utilização de 2,4-D acarretou as menores percentagens de pegamento dos frutos; no 14° dia da aplicação, mais nenhum fruto foi observado. Independentemente do tipo de fitorregulador, os tratamentos não permitiram o desenvolvimento de frutos comerciais de atemoia.

Nutrição mineral de leguminosas tropicais: I. Absorção dos macronutrientes pela centrosema (Centrosema pubescens Benth.), siratro (Macroptilium atropurpureum cv. 'Siratro') e soja perene (Glycine wightii Willd.) cultivadas em condições de campo

As leguminosas tropicais constituem opção como fonte de alimento para o gado, e como revestimento para proteger taludes e aterros contra a erosão. Com a finalidade de se conhecer o habito alimentar das leguminosas tropicais centrosema (Centrosema pubescens Benth.), siratro (Macroptilium atropurpureum cv. 'Siratro') e soja perene (Glycine wightii Willd.) instalou-se o presente ensaio no campo, em Piracicaba, SP, visando obter dados para estabelecer equações para o crescimento, para a concentração e extração dos macronutrientes (N, P, K, Ca, Mg e S), e para a matéria seca digestível das folhas e caules, "in vivo", no bovino, em função da idade da planta. Da apreciação geral dos resultados obtidos, verificou-se diferenças entre as três espécies quanto aos fatores estudados, tais como: a. A máxima produção de matéria seca é da soja perene, seguida pela centrosema e siratro, ocorrendo entre 134 e 140 dias. A maior velocidade no crescimento ocorre entre 83 e 91 dias, para as três espécies. b. O caule apresenta as maiores concentrações de potássio; as folhas, todos os outros macronutrientes. Existem diferenças entre as espécies quanto aos teores de nitrogênio, potássio, cálcio, magnesio e enxofre. O enxofre é absorvido e acumulado continuamente pela centrosema. c. A maior velocidade de acumulação de nitrogênio, fósforo, magnesio e enxofre pelas folhas ocorre entre 80 e 95 dias para as três espécies; de potássio aos 83 e 90 dias para a centrosema e soja perene, respectivamente; de cálcio, aos 116 e 135 dias para a soja perene e siratro. A quantidade maxima e a idade em que ocorre são: d. Existem diferenças na digestibilidade da matéria seca das partes entre as leguminosas. Essa digestibilidade aumenta com a idade da centrosema e do siratro; na soja perene, a digestibilidade mínima ocorre aos 74 dias (39,2%) para o caule e 88 dias (30,2%) para a folha. A matéria seca digestível das folhas de centrosema é 29,8% e das do siratro, 20%, aos 42 dias de idade; aos 147 dias, a da soja perene e 58,8%, seguida do siratro, 56,5%, e da centrosema, 44,0%.