Abstract Resistant bacterial infections represent one of the major threats in worldwide health services. In this scenario, plant essential oils are considered promising antimicrobial agents. Therefore, this study aimed to evaluate the antimicrobial potential of Pectis substriata essential oil alone and in combination with antibiotics, against clinical drug-resistant bacterial strains. The essential oil from the plant aerial parts was obtained by hydrodistillation. Antimicrobial activity was assessed against standard and clinical bacterial strains by broth microdilution method, and the synergistic effect was evaluated by checkerboard microtiter assay. The oil alone showed significant activity against clinical Staphylococcus warneri (62.5 µg.mL-1), and was moderately active on Staphylococcus aureus (standard strain) and clinical Staphylococcus intermedius (125 and 250 µg.mL-1, respectively). Synergism was achieved for the combinations of essential oil and ampicillin on S. warneri and of oil and kanamycin on S. intermedius. Additive effects were also observed. This is the first report of the chemical composition of P. substriata essential oil, and the results revealed the presence of compounds with proven antimicrobial activity. The oil proved active against resistant Gram-positive cocci, and showed synergism with antibiotics, revealing its potential use as adjuvant or in the development of new alternative treatments of drug-resistant antimicrobial infections.

Abstract Objectives: The physicochemical characteristics of bran of cassava starch flour and bran of cassava flour (viz. organoleptic characteristics, pH value, moisture content, total ashes, lipid, protein, starch and fiber contents) and biopharmacotechnical parameters (viz. granulometry, flow capacity, angle at rest, outflow time and apparent density) were evaluated aiming at assessing their potential use as tablet excipients. Methodos: Three tablet formulations of venlafaxine hydrochloride were proposed, having as excipients bran of cassava flour, bran of cassava starch flour and Starch 1500®. The tablets were produced using two different pressures (98±5 MPa and 32±6 Mpa) and their mechanical (hardness and friability) and dissolubility characteristics were evaluated. Results and Conclusions: The tablets produced with both cassava flours, using higher pressures, presented similar physicochemical characteristics to those obtained with the excipient Starch1500®, thus indicating that cassava flours possess the potential to be used as disintegrating agents in tablets.

Resumen Objetivos: Se evaluaron características físico-químicas del salvado de harina y del salvado de la fécula de mandioca (características organolépticas, pH, humedad, cenizas totales y contenido de lípidos, proteínas, almidones y fibras) y biofarmacotécnicas (granulometría, capacidad de flujo, ángulo en reposo, tiempo de salida y densidad aparente) con el objetivo de evaluar el uso de estos residuos como excipientes para comprimidos. Métodos: Se propusieron tres formulaciones en comprimidos de venlafaxina teniendo como excipientes salvado de harina de mandioca, salvado de fécula de mandioca y Starch 1500 ®. Las pastillas se produjeron utilizando dos presiones diferentes (98 ± 5 MPa y 32 ± 6 Mpa). Las características mecánicas (dureza y friabilidad) y de disolución de los comprimidos se evaluaron. Resultados y Conclusiones: Los comprimidos producidos con ambos salvados de mandioca, utilizando las presiones más elevadas, presentaron características físico-químicas similares a las obtenidas con el excipiente Starch1500®, indicando que las harinas de mandioca poseen potencial para ser utilizadas como agentes desintegrantes en comprimidos.

ABSTRACT The increase of incidences of Hepatocellular Carcinoma (HCC) will continue in the next decades. The therapies about hepatitis C infection has been questioned as a risk factor. Some authors emphasized that sustained virologic response (SVR) with interferon- based therapy reduced the risk of developing HCC. In contrast, some publications that to suggest an increasing risk of HCC in patients treated with Direct-Acting Antivirals (DAA). Whether these therapies are associated with an increased risk of HCC remains to be studied and continued long-term observational studies will be needed. The goal in HCV care needs to go beyond merely achieving an SVR.

ABSTRACT Introduction. Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. Materials and methods. We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 lU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for < 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVRI 2) in patients with HCV RNA < 15 lU/mL at their last measurement prior to transplant. Results. Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVRI 2 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA < 15 lU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. Conclusion. Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.

Abstract In a previous study, we reported the antispasmodic and gastroprotective effects of the Serjania caracasana (Jacq.) Willd., Sapindaceae, extract. In the present study, we evaluated the LD50, hemolytic and antispasmodic activities of its fractions and characterized its major constituents by isolation and GC–MS. The animals showed non-toxic symptoms with oral doses up to 2000 mg/kg, suggesting a safe oral administration. Furthermore, a low hemolytic activity was detected for the saponin fraction. Antispasmodic activity of the fractions was evaluated through carbachol-induced contractions in rat ileum. The hexane fraction was the most potent (IC50 68.4 ± 5.9 µg/ml) followed by the dichloromethane fraction (IC50 161.3.4 ± 40.7 µg/ml). Butanol fraction was the less effective (IC50 219.8 ± 60.3 µg/ml). The phytochemical study of the S. caracasana fractions afforded the isolation of friedelin, β-amyrin, allantoin and quercitrin. This is the first time that the presence of allantoin and quercitrin in the Serjania genus has been reported. Among the isolated compounds and those characterized by GC–MS, β-amyrin and β-sitosterol were present in the most active fractions, hexane and dichloromethane, and they may be related to its antispasmodic activity. In addition, spathulenol was only found in the hexane fraction and its presence might justify the highest antispasmodic activity observed for this fraction.

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

ABSTRACT Background. Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. Objectives. To examine the risk factors in the development of CRF in these patients. Material and methods. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Results. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. Conclusions. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

ABSTRACT Genetic parameters for reproductive traits in female Nile tilapia were estimated in this study using Bayesian inference method. The data set presented information from 451 Nile tilapia females that were evaluated at two different places in Maringá - Paraná - Brazil (hapas of 1 and 10 m³) and at one location in Alfenas - Minas Gerais - Brazil. A spawning examination was conducted once a week from October 2012 to March 2013 for a total of 23 weeks of evaluation. Single-trait analyses for spawning success, multiple spawning, spawning frequency, and volume of eggs/female were performed by using the software MTGSAM Threshold. The heritability estimates were 0.14, 0.16, 0.53, and 0.08 for spawning success, multiple spawning, spawning frequency and volume of eggs/female, respectively, indicating it is possible to achieve a substantial genetic gain using these reproductive traits as selection criteria.

Abstract Liquid flow in the impeller swept region of vessels with a turbine-type agitator was examined for the flow path between the neighboring blades of the rotating impeller. Visualization of the flow and its measurement were done using particle tracking velocimetry with a camera rotating along with the impeller. Internal liquid flow of the impeller differed when the velocity magnitudes were compared in conditions with and without baffles. Larger circumferential and radial velocities were observed without the baffles and with the baffles, respectively, which was considered to result in the difference of impeller power transmission. Efficiencies produced, based on the flow-head concept, reflected the impeller power characteristics. The turbine-type impeller as an actuator was demonstrated to improve in the flow characteristics with viscous losses increased by the baffles. In terms of impeller efficiencies based on the power consumption, the effect of baffles for the energy was as a decreased transmission and an increased transport.

OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2) concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036). CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

Lamivudina e efavirenz estão entre os fármacos mais utilizados em todo o mundo para o tratamento da síndrome da imunodeficiência adquirida (AIDS). Foram utilizadas as técnicas de ressonância magnética nuclear de estado sólido (ssNMR), espectroscopia no infravermelho por transformada de Fourier (FTIR), calorimetria exploratória diferencial (DSC), e análise termo-óptica (TOA) para estudar possíveis interações entre esses fármacos, visando o desenvolvimento de uma combinação em dose fixa dos mesmos. DSC e TOA evidenciaram deslocamentos significantes das temperaturas de fusão dos fármacos na mistura, o que sugere uma interação entre eles. Apesar de os resultados de DSC e TOA indicarem incompatibilidade entre as drogas, os espectros de FTIR não apresentaram modificações devido à sobreposição de bandas. As análises de ssNMR mostraram mudanças significativas nos valores de deslocamento químico da mistura quando comparados aos dos fármacos puros, especialmente nos sinais referentes a átomos de carbono deficientes em elétrons. Essses resultados confirmam as interações sugeridas pelo DSC e TOA, devido provavelmente a interações ácido-base entre átomos eletronegativos e deficientes em elétrons dos fármacos.

Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz.

O alcalóide azafluorenona 5,8-dimetóxi-7-hidróxi-1-metil-4-azafluoren-9-ona e o megastigmano (-)-(5R*, 6S*)-megastigman-3-ona-10,7-olidio foram isolados das partes aéreas de Unonopsis lindmanii (Annonaceae), juntamente com os compostos conhecidos (3S*, 5S*, 8R*)-3,5-di-hidróxi-megastigma-6,7-dien-9-ona (grasshopper ketone), N-trans-feruloiltiramina, (-)-anonaína, (-)-asimilobina, liriodenina e (-)-siringaresinol. Este é o primeiro relato da presença de megastigmanos em Annonaceae. As estruturas dos compostos foram elucidadas com base em dados espectroscópicos.

The azafluorenone alkaloid 5,8-dimethoxy-7-hydroxy-1-methyl-4-azafluoren-9-one and the megastigman (-)-(5R*, 6S*)-megastigman-3-one-10,7-olide were isolated from aerial parts of Unonopsis lindmanii (Annonaceae), along with the known compounds (3S*, 5S*, 8R*)-3,5-dihydroxy-megastigma-6,7-dien-9-one (grasshopper ketone), N-trans-feruloyltyramine, (-)-anonaine, (-)-asimilobine, liriodenine and (-)-syringaresinol. This is the first description of the presence of megastigmanes in Annonaceae. The structures of the compounds were elucidated based on spectroscopic data.

Thin films of PbTiO3 were deposited at a temperature of 400°C onto Pt/Ti/SiO2/Si <100> substrates by the aerosol assisted CVD method using organometallic precursors. With the purpose of stabilizing and homogenizing the Perovskite phase, the films were annealed at 550°C, in a Pb-rich atmosphere, for 12 h. Thermogravimetric analysis of the precursors were performed to determine the theoretical temperature of deposition. The crystallinity of the phase before and after annealing was characterized by grazing incidence x-ray diffraction. Additionally, microstructural analysis using scanning (SEM) and transmission (TEM) electron microscopy was also performed.

Se depositaron películas delgadas de PbTiO3 (PT) a temperatura de 400°C en un sustrato de Pt/Ti/SiO2/Si <100> por el método de depósito químico asistido por aerosol (CVD-AA) usando precursores organometálicos. Con el propósito de estabilizar la fase Perovskita, la película fue recocida a temperaturas de 550°C por 12 horas, en una atmósfera rica en Pb. Se realizaron análisis termogravimétricos de los precursores con la finalidad de conocer la temperatura teórica de depósito. La cristalinidad de la fase antes y después del recocido fue caracterizada por difracción de rayos-X a incidencia rasante. Por otro lado, también se realizó análisis microestructural por microscopias electrónicas de barrido (MEB) y de trasmisión (MET).

Clorofila, um pigmento natural termossensível, foi incorporado à matriz de filmes de quitosana visando a obter sistemas inteligentes de indicação de variação de temperatura. A quitosana é um polímero biodegradável que forma filmes flexíveis com eficiente barreira ao oxigênio, podendo ser alternativa ao uso de polímeros sintéticos. Clorofila foi adicionada (0,25 g/100 g) à suspensão de quitosana (2,00 g/100 g) formando filmes inteligentes de quitosana (FIQ). Os efeitos da temperatura (10 °C a 50 °C) e luminosidade (0 a 1000 lx) foram estudados utilizando um planejamento experimental, avaliando os parâmetros de cor (L*, a*, b*) e propriedades mecânicas. As suspensões de quitosana contendo clorofila foram aplicadas como revestimento em superfície de papel cartão formando o sistema de material flexível filme-papel cartão (S-FP), reduzindo significativamente o tempo de secagem. Os filmes caracterizaram-se pela homogeneidade, flexibilidade, coloração esverdeada e fácil manuseio. A variação de cor foi visualmente observada no sistema S-FP, alterando irreversivelmente de verde para amarelo quando submetido a temperaturas acima de 50 °C, independentemente da luminosidade. Desta forma, o sistema proposto tem potencial de aplicação como indicador colorimétrico de temperatura na faixa de 50 °C a 75 °C, com a vantagem de simples fabricação, biodegradabilidade e uso de materiais seguros para aplicação em contato direto com alimentos e fármacos, além do baixo custo.

Chlorophyll was incorporated into chitosan films, forming intelligent systems able to detect variations in temperature. Chitosan is a biodegradable polymer that forms flexible, resistant films with an efficient oxygen barrier. Chlorophyll was added (0.25 g/100 g) into chitosan suspension (2.00 g/100 g) and intelligent films (FIQ) were cast. The effects of temperature (10 °C to 50 °C) and luminosity (0 to 1000 lx) on the films were studied using an experimental design with two variables, analyzing the color parameters L*, a*, b* and mechanical properties. The films were characterized according to their homogeneity, flexibility, color and handling. Chitosan suspensions containing chlorophyll were also applied as coating on the surface of pieces of card-paper, forming a card paper film system (S-FP). By visual inspection we observed the color of the S-FP changing irreversibly from green to yellow when the temperature was above 50 °C. Therefore, the S-FP system can potentially be used as a colorimetric indicator for the 50 °C to 70 °C range, being advantageous owing to the ease of fabrication, biodegradability, safe use for food and low cost.