Antimicrobial and cytotoxic assessment of marine cyanobacteria - synechocystis and synechococcus

Aqueous extracts and organic solvent extracts of isolated marine cyanobacteria strains were tested for antimicrobial activity against a fungus, Gram-positive and Gram-negative bacteria and for cytotoxic activity against primary rat hepatocytes and HL-60 cells. Antimicrobial activity was based on the agar diffusion assay. Cytotoxic activity was measured by apoptotic cell death scored by cell surface evaluation and nuclear morphology. A high percentage of apoptotic cells were observed for HL-60 cells when treated with cyanobacterial organic extracts. Slight apoptotic effects were observed in primary rat hepatocytes when exposed to aqueous cyanobacterial extracts. Nine cyanobacteria strains were found to have antibiotic activity against two Gram-positive bacteria, Clavibacter michiganensis subsp. insidiosum and Cellulomonas uda. No inhibitory effects were found against the fungus Candida albicans and Gram-negative bacteria. Marine Synechocystis and Synechococcus extracts induce apoptosis in eukaryotic cells and cause inhibition of Gram-positive bacteria. The different activity in different extracts suggests different compounds with different polarities.

Towards a reliable technology for antioxidant capacity and oxidative damage evaluation: Electrochemical (bio)sensors

To counteract and prevent the deleterious effect of free radicals the living organisms have developed complex endogenous and exogenous antioxidant systems. Several analytical methodologies have been proposed in order to quantify antioxidants in food, beverages and biological fluids. This paper revises the electroanalytical approaches developed for the assessment of the total or individual antioxidant capacity. Four electrochemical sensing approaches have been identified, based on the direct electrochemical detection of antioxidant at bare or chemically modified electrodes, and using enzymatic and DNA-based biosensors.

Arylhydrazones of barbituric acid: synthesis, coordination ability and catalytic activity of their CoII, CoII/IIIand CuIIcomplexes toward peroxidative oxidation of alkanes

New ortho-substituted arylhydrazones of barbituric acid, 5-(2-(2-hydroxyphenyl)hydrazono) pyrimidine-2,4,6(1H,3H,5H)-trione (H4L1) and the sodium salt of 2-(2-(2,4,6-trioxotetra-hydropyrimidin-5(2H)-ylidene)hydrazinyl) benzenesulfonic acid (H4L2), [Na(H3L2)(mu-H2O)(H2O)(2)](2) (1), were used in the synthesis of Cu-II, Co-II and Co-II/III complexes, [Cu(H2L1)(H2O)(im)]center dot 3H(2)O (im = imidazole) (2), [Co(H2O)(6)] [Co(H2L1)(2)](2)center dot 8H(2)O (3), [Co(H2L2)(im)(3)] (4), [Cu(H2L2)(im)(2)]center dot H2O (5) and [Co(H2O)(6)][H3L2](2)center dot 8H(2)O (6). The complexes are water soluble and the mono-or di-deprotonated ligands display different coordination modes, depending on the synthetic conditions. The electrochemical behaviour of all the compounds was investigated by cyclic voltammetry and controlled potential electrolysis, revealing that the ligands are also redox active. All the compounds were evaluated as catalysts for the peroxidative (with H2O2) oxidation of cyclohexane at room temperature. The compounds 2 and 3 are the most active ones (yields up to 21% and TON up to 213 are achieved, in the presence of 3).

EVALUATION OF ANTIMICROBIAL AND CYTOTOXIC ACTIVITIES OF PLANT EXTRACTS FROM SOUTHERN MINAS GERAIS CERRADO

The antimicrobial activity of plant hidroethanolic extracts on bacteria Gram positive, Gram negative, yeasts, Mycobacterium tuberculosis H37 and Mycobacterium bovis was evaluated by using the technique of Agar diffusion and microdilution in broth. Among the extracts evaluated by Agar diffusion, the extract of Bidens pilosa leaf presented the most expressive average of haloes of growth inhibition to the microorganisms, followed by the extract of B. pilosa flower, of Eugenia pyriformis' leaf and seed, of Plinia cauliflora leaf which statistically presented the same average of haloes inhibitory formation on bacteria Gram positive, Gram negative and yeasts. The extracts of Heliconia rostrata did not present activity. Mycobacterium tuberculosis H37 and Mycobacterium bovis(BCG) appeared resistant to all the extracts. The susceptibility profile of Candida albicans and Saccharomyces cerevisiae fungi were compared to one another and to the Gram positive Bacillus subtilis, Enterococcus faecalis and the Gram negative Salmonella typhimurium bacteria (p > 0.05). The evaluation of cytotoxicity was carried out on C6-36 larvae cells of the Aedes albopictus mosquito. The extracts of stem and flower of Heliconia rostrata, leaf and stem of Plinia cauliflora, seed of Anonna crassiflora and stem, flower and root of B. pilosa did not present toxicity in the analyzed concentrations. The highest rates of selectivity appeared in the extracts of stem of A. crassiflora and flower of B. pilosa to Staphylococcus aureus, presenting potential for future studies about a new drug development.

Antioxidant, cytotoxic and UVB-absorbing activity of Maytenus guyanensis Klotzch. (Celastraceae) bark extracts

Maytenus guyanensis Klotzch. is an Amazonian medicinal tree species known in Brazil by the common name chichuá and in Peru and Colombia by the name chuchuhuasi. It is used in traditional medicine as stimulant, tonic, and muscle relaxant, for the relief of arthritis, rheumatism, hemorrhoids, swollen kidney, skin eruptions, and skin cancer prevention, among others. Initially, different extraction solvents and methods were applied to dried, ground bark which made possible the preparation of extracts having both significant lethality to brine shrimp larvae (Artemia franciscana Leach) as well as antioxidant activity in vitro based on tests involving reactions with 2,2,-diphenyl-1-picrylhydrazyl (DPPH). Analysis of fractions from serial extractions with solvents of increasing polarity supports the notion that antioxidant activity is associated with compounds of intermediate polarity and cytotoxicity is associated with compounds of low to intermediate polarity. Variation of extraction time and conditions revealed that hot, continuous ethanol extraction provided good yields of bark extract in several hours. Hot extraction also provided ethanol extracts having greater lethality to brine shrimp and antioxidant activity (compared to the flavonoid rutin in semi-quantitative methods based on DPPH) than extracts obtained from maceration at room temperature. Freeze-dried ethanol extracts were prepared by: 1) maceration at room temperature and 2) hot extraction (eight hours) on several hundred gram scales and the latter extract was shown to have partial screening effects on UVB light. In this work, cytotoxic, antioxidant and potential sun-screening activity are shown for the first time in M. guyanensis.

Microencapsulation of ellagic acid from pomegranate husk and karaya gum by spray drying

Objective: The aim of this study was to obtain and characterize microcapsules with Ellagic Acid (EA) from pomegranate as core material and Karaya Gum (KG) as wall material. Methods: EA was obtained from dry pomegranate peel powder via methanolysis and quantified by HPLC. Microcapsules were obtained preparing a dispersion containing KG and EA in phosphate buffer pH 8. The dispersion was processed in a spray dryer under specific conditions (inlet temperature at 150 °C, feed flow at 30% and aspirator at 100 %) for obtaining of microcapsules. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used for characterization. Results: Obtained material contains 98.03±2.82 mg EA/g of pomegranate peel. FTIR showed that there were changes in the molecular structure of microcapsules referred to raw materials. SEM confirmed that particles obtained had micron-size (1-5 µm). DSC analysis showed that raw materials had glass transition temperatures of 79.58 and 83.41 °C and for microcapsules the value was67.25 °C. Conclusion: Methanolysis is a viable technique for the obtaining of EA from the peel of pomegranate. KG shows good potential for be used as wall material for EA microencapsulation.

Effect of acid or alkaline catalyst and of different capping agents on the optical properties of CdS nanoparticles incorporated within a diureasil hybrid matrix

CdS nanoparticles (NPs) were synthesized using colloidal methods and incorporated within a diureasil hybrid matrix. The surface capping of the CdS NPs by 3-mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) organic ligands during the incorporation of the NPs within the hybrid matrix has been investigated. The matrix is based on poly(ethylene oxide)/poly(propylene oxide) chains grafted to a siliceous skeleton through urea bonds and was produced by sol–gel process. Both alkaline and acidic catalysis of the sol–gel reaction were used to evaluate the effect of each organic ligand on the optical properties of the CdS NPs. The hybrid materials were characterized by absorption, steady-state and time-resolved photoluminescence spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM). The preservation of the optical properties of the CdS NPs within the diureasil hybrids was dependent on the experimental conditions used. Both organic ligands (APTMS and MPTMS) demonstrated to be crucial in avoiding the increase of size distribution and clustering of the NPs within the hybrid matrix. The use of organic ligands was also shown to influence the level of interaction between the hybrid host and the CdS NPs. The CdS NPs showed large Stokes shifts and long average lifetimes, both in colloidal solution and in the xerogels, due to the origin of the PL emission in surface states. The CdS NPs capped with MPTMS have lower PL lifetimes compared to the other xerogel samples but still larger than the CdS NPs in the original colloidal solution. An increase in PL lifetimes of the NPs after their incorporation within the hybrid matrix is related to interaction between the NPs and the hybrid host matrix.

Poly lactic acid based biodegradable stents and functionalization techniques: brief review

Commercial stents, especially metallic ones, present several disadvantages, and this gives rise to the necessity of producing or coating stents with different materials, like natural polymers, in order to improve their biocompatibility and minimize the disadvantages of metallic ones. This review paper discusses some applications of natural-based polymers in stents, namely polylactic acid (PLA) for stent development and chitosan for biocompatible coatings of stents . Furthermore, some effective stent functionalization techniques will be discussed, namely Layer by Layer (LBL) technique.

Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development

Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.

Producción de ácido Itacónico por Aspergillus terreus y de Ácido Hialurónico por Streptococcus equi subsp. equi en Biorreactores de Tanque Agitado. Production of Itaconic Acid by Aspergillus terreus and of Hyaluronic Acid by Sreptococcus equi subsp. equi in Stirred Tank Bioreactors.

El proyecto aborda el problema general de establecer una metodología para el cambio de escala de la producción de metabolitos en biorreactores de tanque agitado.En el desarrollo de procesos de producción de metabolitos a partir de microorganismos, el cambio de escala es particularmente complejo, dado que los microorganismos experimentan un continuo cambio en sus rutas metabólicas durante el período de producción. Esto hace que en el proceso del cambio de escala, las mayores dificultades se encuentren en el desarrollo del inóculo y problemas ocasionados por modificaciones en las características de transferencia de calor, masa y momento.Dentro de este contexto general se definen dos objetivos específicos. Estos son: el estudio de la producción de ácido itacónico por Aspergillus terreus y el de la producción de ácido hialurónico por Streptococcus equi. subsp. equi, con la finalidad de desarrollar una metodología de trabajo experimental y teórica que permita sistematizar el estudio del factibilidad técnico-económica de plantas de producción, vinculando la investigación del procesos a escala de laboratorio con la producción a mayor escala.La hipótesis de trabajo es que el estudio de la producción de Aspergillus terreus y de Streptococcus equi en un biorreactor de tanque agitado a escala de laboratorio permitirá establecer los parámetros que contribuirán a realizar el cambio de escala de su producción y esto será verificado experimentalmente.Los trabajos se realizarán utilizando un biorreactor a escala de laboratorio especialmente diseñado para este tipo de trabajo. Los resultados experimentales se interpretarán con técnicas estadísticas y matemáticas de diferente complejidad a efectos de establecer los criterios de cambio de escala y luego se realizarán experiencias en un biorreactor piloto con el objeto de verificar la metodología seleccionada.El desarrollo del proyecto permitirá:1.- obtener información técnica útil sobre la producción de ácido itacónico, el que tiene importantes aplicaciones en la industria del plástico. La producción por medio del Aspergillus terreus MJL05 se realizará utilizando glicerol como fuente de carbono, el que constituye el principal subproducto en los procesos de manufactura de biodiesel. De este modo se podrá analizar la factibilidad técnica de una ruta alternativa para emplear este subproducto.2.- obtener información técnica útil sobre la producción de ácido hialurónico, biopolímero de alto valor agregado con importantes aplicaciones en medicina, y contribuir así a realizar el cambio de escala de su producción.

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results.

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.

Orosomucoid (alpha1-acid glycoprotein) plasma concentration and genetic variants: effects on human immunodeficiency virus protease inhibitor clearance and cellular accumulation.

BACKGROUND AND OBJECTIVE: Protease inhibitors are highly bound to orosomucoid (ORM) (alpha1-acid glycoprotein), an acute-phase plasma protein encoded by 2 polymorphic genes, which may modulate their disposition. Our objective was to determine the influence of ORM concentration and phenotype on indinavir, lopinavir, and nelfinavir apparent clearance (CL(app)) and cellular accumulation. Efavirenz, mainly bound to albumin, was included as a control drug. METHODS: Plasma and cells samples were collected from 434 human immunodeficiency virus-infected patients. Total plasma and cellular drug concentrations and ORM concentrations and phenotypes were determined. RESULTS: Indinavir CL(app) was strongly influenced by ORM concentration (n = 36) (r2 = 0.47 [P = .00004]), particularly in the presence of ritonavir (r2 = 0.54 [P = .004]). Lopinavir CL(app) was weakly influenced by ORM concentration (n = 81) (r2 = 0.18 [P = .0001]). For both drugs, the ORM1 S variant concentration mainly explained this influence (r2 = 0.55 [P = .00004] and r2 = 0.23 [P = .0002], respectively). Indinavir CL(app) was significantly higher in F1F1 individuals than in F1S and SS patients (41.3, 23.4, and 10.3 L/h [P = .0004] without ritonavir and 21.1, 13.2, and 10.1 L/h [P = .05] with ritonavir, respectively). Lopinavir cellular exposure was not influenced by ORM abundance and phenotype. Finally, ORM concentration or phenotype did not influence nelfinavir (n = 153) or efavirenz (n = 198) pharmacokinetics. CONCLUSION: ORM concentration and phenotype modulate indinavir pharmacokinetics and, to a lesser extent, lopinavir pharmacokinetics but without influencing their cellular exposure. This confounding influence of ORM should be taken into account for appropriate interpretation of therapeutic drug monitoring results. Further studies are needed to investigate whether the measure of unbound drug plasma concentration gives more meaningful information than total drug concentration for indinavir and lopinavir.

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.