Diatom aggregation when exposed to crude oil and chemical dispersant: Potential impacts of ocean acidification.

Diatoms play a key role in the marine carbon cycle with their high primary productivity and release of exudates such as extracellular polymeric substances (EPS) and transparent exopolymeric particles (TEP). These exudates contribute to aggregates (marine snow) that rapidly transport organic material to the seafloor, potentially capturing contaminants like petroleum components. Ocean acidification (OA) impacts marine organisms, especially those that utilize inorganic carbon for photosynthesis and EPS production. Here we investigated the response of the diatom Thalassiosira pseudonana grown to present day and future ocean conditions in the presence of a water accommodated fraction (WAF and OAWAF) of oil and a diluted chemically enhanced WAF (DCEWAF and OADCEWAF). T. pseudonana responded to WAF/DCEWAF but not OA and no multiplicative effect of the two factors (i.e., OA and oil/dispersant) was observed. T. pseudonana released more colloidal EPS (< 0.7 µm to > 3 kDa) in the presence of WAF/DCEWAF/OAWAF/OADCEWAF than in the corresponding Controls. Colloidal EPS and particulate EPS in the oil/dispersant treatments have higher protein-to-carbohydrate ratios than those in the control treatments, and thus are likely stickier and have a greater potential to form aggregates of marine oil snow. More TEP was produced in response to WAF than in Controls; OA did not influence its production. Polyaromatic hydrocarbon (PAH) concentrations and distributions were significantly impacted by the presence of dispersants but not OA. PAHs especially Phenanthrenes, Anthracenes, Chrysenes, Fluorenes, Fluoranthenes, Pyrenes, Dibenzothiophenes and 1-Methylphenanthrene show major variations in the aggregate and surrounding seawater fraction of oil and oil plus dispersant treatments. Studies like this add to the current knowledge of the combined effects of aggregation, marine snow formation, and the potential impacts of oil spills under ocean acidification scenarios.

Efeito da adição de óleo de licuri (Syagrus coronata) e Tween 80 em filme de amido de araruta (Maranta arundinacea L. ) / Effect of the addition of licuri oil (Syagrus coronata) and Tween 80 in a film of araruta starch (Maranta arundinacea L. )

O objetivo de trabalho foi avaliar o efeito da adição de óleo de licuri nas propriedades do filme a base de amido de araruta (bioplástico). Foram elaborados dois filmes, um conteúdo óleo de licuri e outro sem o óleo na formulação. Os filmes foram caraterizados através de analises de espessura, solubilidade, atividade de água, permeabilidade a vapor de água, ensaios de tração e analise de cor. Os resultados apontaram que o óleo de licuri reduziu a resistência á tração, o modulo de Young, a atividade de água, a solubilidade e a luminosidade dos filmes de amido de araruta. Além disso, a adição do óleo levou à um aumento da espessura e permeabilidade ao vapor de água. A adição de óleo de licuri influenciou de forma favorável algumas propriedades do filme a base de amido de araruta.

Biosurfactant-modified palygorskite clay as solid-stabilizers for effective oil spill dispersion.

An effective and conventional remediation technique in marine oil spills is to apply chemical dispersants to emulsify oil slicks into small oil droplets. Still, the potential hazards of chemical dispersants onto the marine ecosystem have motivated the research for environmentally friendly alternative while keeping exceptional dispersion ability. Here, we showed that the mixture of palygorskite (PAL) and rhamnolipid (Rha) formed a biocompatible alternative to synthetic surfactants used for oil spill dispersion. The oil droplets dispersed by R-PAL presented a small average size and long-term stability, which illustrated the synergistic interactions between Rha and PAL acting as an efficient dispersant in artificial sea water (ASW). Due to the strong flocculation caused by high salinity, PAL alone was not effective emulsifiers in ASW. A small amount of Rha could played a major role in modifying the surface characteristics of PAL and decreasing oil-water interfacial tension. Therefore, PAL particles irreversibly adsorbed onto the oil-ASW interface and formed a rigid interfacial film around oil droplets in the presence of Rha, which offered an efficient barrier to droplet coalescence. The synergistic interactions between PAL and Rha could enable the dispersion of tetradecane in ASW. Such a functionality was further tested in dispersing crude oil in ASW. The study presents a new strategy of using a mixture of PAL and Rha for oil dispersion, thus providing an ecofriendly alternative to conventional dispersants.

Are additive effects of dietary surfactants on intestinal tight junction integrity an overlooked human health risk? - A mixture study on Caco-2 monolayers.

Surfactants may cause dysfunction of intestinal tight junctions (TJs), which is a common feature of intestinal autoimmune diseases. Effects of dietary surfactants on TJ integrity, measured as trans-epithelial resistance (TEER), were studied in Caco-2 cell monolayers. Cytotoxicity was assessed as apical LDH leakage. Monolayers were apically exposed for 60 min to the dietary surfactants solanine and chaconine (SC, potato glycoalkaloids, 0-0.25 mM), perfluorooctane sulfonic acid (PFOS, industrial contaminant, 0-0.8 mM), and sucrose monolaurate (SML, food emulsifier E 473, 0-2.0 mM) separately and as a mixture. Dose-response modelling of TEER EC50 showed that SC were 2.7- and 12-fold more potent than PFOS and SML, respectively. The mixture was composed of 1 molar unit SC, 2.7 units PFOS and 12 units SML ("SC TEER equivalent" proportions 1:1:1). Mixture exposure (0-0.05 mM SC equivalents) dose-response modelling suggested additive action on TJ integrity. Increasing SC and SML concentrations caused increased LDH leakage, but PFOS decreased LDH leakage at intermediate exposure concentrations. In the mixture PFOS appeared to protect from extensive SC- and SML-induced LDH leakage. Complex mixtures of surfactants in food may act additively on intestinal TJ integrity, which should be considered in risk assessment of emulsifier authorisation for use in food production.

Phase behavior and formation of o/w nano-emulsion in vegetable oil/ mixture of polyglycerol polyricinoleate and polyglycerin fatty acid ester/water systems.

It is reported that mixing polyglycerol polyricinoleate (PGPR) and polyglycerol laurilester has a great emulsifying capacity, and consequently fine oil-in-water (o/w) emulsions can be formed. However, the role of PGPR is not clear. The objective of this research is to investigate the phase behavior of vegetable oil/mixture of PGPR and polyglycerol fatty acid ester/water systems, and to clarify the role of PGPR in making a fine emulsion. Phase diagrams were constructed to elucidate the optimal process for preparing fine emulsions. In all the systems examined in this study, the phases, including the liquid crystal phase (L(c)) and sponge phase (L(3)), spread widely in the phase diagrams. We examined droplet size of the emulsions prepared from each phase and found that o/w nano-emulsions with droplet sizes as small as 50 nm were formed by emulsifying either from a single L(3) phase or a two-phase region, L(c) + L(3). These results indicate that a sponge phase L(3) or liquid crystal phase L(c) or both is necessary to form an o/w nano-emulsion whose average droplet diameter is less than 50 nm for PGPR and polyglycerin fatty acid ester mixtures used as surfactant.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

UNLABELLED: Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. OBJECTIVES: To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. METHODS: A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. CONCLUSIONS: Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Occupational contact allergy to cocamidopropyl betaine and its impurities.

BACKGROUND: Contact allergy to cocamidopropyl betaine has been attributed to its impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. OBJECTIVES: To describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic. METHODS: We reviewed the 2002-2009 patch test records at the Finnish Institute of Occupational Health for allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine, cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant reactions to at least one of the test substances were seen in 39% of the 1092 patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl dimethylamine were common. Ten of the 15 patients were diagnosed with occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds. The sources of occupational exposure included hair care products, hair colours, perm wave solutions, and liquid soaps. Multiple contact allergies and exposure to several irritant factors were common, and all patients had hand eczema. CONCLUSIONS: Patch test reactions to cocamidopropyl betaine-related compounds are difficult to interpret, owing to extremely common irritant reactions. Cocamidopropyl betaine itself is probably not an allergen. Occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds is relatively rare and, unlike non-occupational cocamidopropyl betaine-related allergy, typically manifests as hand dermatitis.

Assessment of drug-lipid complex formation by a high-throughput Langmuir-balance and correlation to phospholipidosis.

Phospholipidosis, the accumulation of phospholipids in cells, is a relatively frequent side effect of cationic amphiphilic drugs. In response to the industry need, several methods have been recently published for the prediction of the phospholipidosis-inducing potential of drug candidates. We describe here a high-throughput physicochemical approach, which is based on the measurement of drug-phospholipid complex formation observed by their effect on the critical micelle concentration (CMC) of a short-chain acidic phospholipid. The relative change due to the drug, CMC(DL)/CMC(L) provides a direct measure of the energy of the drug-phospholipid association, irrespective of the nature of the interaction. Comparison of results for 53 drugs to human data, animal testing, cell culture assays, and other screening methods reveals very good correlation to their phospholipidosis-inducing potential. The method is well suited for screening already in early phases of drug discovery.

In vitro and in vivo evaluation of Bola-surfactant containing niosomes for transdermal delivery.

A novel niosome formulation is proposed for topical drug delivery of ammonium glycyrrhizinate, a natural compound with an efficacious anti-inflammatory activity. Niosomes were made up of a new non ionic surfactant, alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio). Niosome vesicles were prepared with the thin layer evaporation method and were physico-chemically characterized. The tolerability of Bola-surfactant both as free molecules or assembled ion niosome vesicles was evaluated in vitro on cultured of human keratinocyte cells (NCTC2544). Human tolerability was evaluated on volunteers. The ability of Bola-niosomes to promote intracellular delivery was evaluated by confocal laser scanning microscopy (CLSM) studies. Human stratum corneum and epidermis (SCE) membranes were used in vitro to investigate the percutaneous permeation. The anti-inflammatory activity of ammonium glycyrrhizinate was evaluated in vivo on human volunteers with a chemically induced erythema. Experimental data show that Bola-niosomes are characterized by a mean size of approximately 400 nm and are able to provide an encapsulation efficiency of 40% with respect to the drug amount used during preparation. CLSM showed that Bola-niosomes were able to promote the intracellular uptake of the delivered substances. Bola-niosomes were also able to significantly improve (p<0.001) the percutaneous permeation of ammonium glycyrrhizinate with respect to both the aqueous drug solution and a physical mixture between unloaded Bola-niosomes and the aqueous drug solution. Bola-niosomes showed a suitable tolerability both in vitro and in vivo. Ammonium glycyrrhizinate-loaded Bola-niosomes determined a significant (p<0.001) and noticeable improvement of the in vivo anti-inflammatory activity of the drug. An effective example of conjugating innovative colloidal carriers, coming from pharmaceutical nanotechnology, and therapeutically effective natural compounds, coming from traditional medicine, was reported.

Comparison of different water/oil microemulsions containing diclofenac sodium: preparation, characterization, release rate, and skin irritation studies.

The aim of the present study was to make a comparison of the in vitro release rate of diclofenac sodium (DS) from microemulsion (M) vehicles containing soybean oil, nonionic surfactants (Brij 58 and Span 80), and different alcohols (ethanol [E], isopropyl alcohol [I], and propanol [P]) as cosurfactant. The optimum surfactant:cosurfactant (S:CoS) weight ratios and microemulsion areas were detected by the aid of phase diagrams. Three microemulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity. According to the release rate of DS, M prepared with P showed the significantly highest flux value (0.059 +/- 0.018 mg/cm(2)/h) among all formulations (P < .05). The conductivity results showed that DS-loaded microemulsions have higher conductivity values (18.8-20.2 microsiemens/cm) than unloaded formulations (16.9-17.9 microsiemens/cm), and loading DS into the formulation had no negative effect on system stability. Moreover, viscosity measurements were examined as a function of shear rate, and Newtonian fluid characterization was observed for each microemulsion system. All formulations had appropriate observed pH values varying from 6.70 to 6.85 for topical application. A skin irritation study was performed with microemulsions on human volunteers, and no visible reaction was observed with any of the formulations. In conclusion, M prepared with P may be a more appropriate formulation than the other 2 formulations studied as drug carrier for topical application.

Allergenicity and cross-reactivity of coconut oil derivatives: A double-blind randomized controlled pilot study.

BACKGROUND: Counseling of patients with cocamidopropyl betaine (CAPB) allergy is difficult because the cross-reactivity of CAPB with other coconut-derived surfactants, coconut oil, and coconut fatty acids is largely unknown. OBJECTIVE: To provide pilot data regarding the cross-reactivity and allergenicity of surfactants derived from coconut oil. METHODS: A randomized double-blind controlled pilot study of 10 control patients and 12 patients previously found to be allergic to CAPB. Eleven coconut-derived surfactants, as well as coconut oil and lauric acid, were applied in random order according to standardized patch-test procedures with readings at 48 and 92 hours. The primary outcome measure was the frequency of positive patch-test reactions to each allergen. RESULTS: Only 3 of the 12 patients with previous reactions to CAPB reacted on retesting, and all of these reactions were doubtful. Fifty-nine percent of the study patients had reactions to triethanolamine polyethylene glycol-3 (TEA-PEG-3) cocamide sulfate as compared to none of the controls (p = .005). CONCLUSIONS: Reactions to CAPB were only 25% reproducible. These results substantiate previous experience that doubtful and mild reactions to CAPB may represent irritant reactions as opposed to true allergic reactions. TEA-PEG-3 cocamide sulfate was the only agent that had a statistically significant higher rate of reactions in the study group as compared to the control group.

Validation of an in vitro screen for phospholipidosis using a high-content biology platform.

Several cationic amphiphilic drugs cause local or systemic phospholipidosis (PLD) after chronic exposure in preclinical species. PLD is characterized by the accumulation of drug, phospholipid, and concentric lamellar bodies in cellular lysosomes. We have developed a fluorescence-based in vitro screen that is predictive of PLD using the Cellomics ArrayScan high-content screening platform, which captures and analyzes images from 96-well cell culture microtiter plates using multichannel fluorescence microscopy. I-13.35 adherent mouse spleen macrophage cells were cultured with drug and a fluorescently tagged phospholipid, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE). Drug concentrations were used in a range from 1 to 100 micro mol/L. After 24 h incubations, the cells were fixed with formalin. NBD-PE uptake was quantified in controls and treated cells. Nuclei were identified by Hoechst 33258 staining and dead cells were identified using ethidium homodimer-2 incorporation. Thus, confounding accumulation of NBD-PE due to cytotoxicity that produces false-positive results at high concentrations was eliminated from quantitation by ethidium staining and employing cell gating (dead cell rejection). The assay was found to be both sensitive and selective in that 26 of 28 positive, phospholipidogenic controls and 8 of 8 negative, non-phospholipidogenic controls were correctly called.

In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D,L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation.

This work shows a full spectrum of research on Vitamin E TPGS-emulsified Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for paclitaxel formulation to improve its therapeutic index and to reduce the adverse effects of adjuvant Cremophor EL in its current clinical formulation of Taxol. Paclitaxel-loaded PLGA NPs were prepared by a modified solvent extraction/evaporation technique with vitamin E TPGS as emulsifier. The formulated NPs were found in quite uniform size of approximately 240 nm diameter. The in vitro drug release profile exhibited a biphasic pattern with an initial burst followed by a sustained release. In vitro HT-29 cell viability experiment demonstrated that the drug formulated in the NPs was 5.64, 5.36, 2.68, and 1.45 times more effective than that formulated in the Taxol formulation after 24, 48, 72, 96 h treatment, respectively at 0.25 microg/mL drug concentration, which should be even better with the sustainable release feature of the NPs formulation considered. In vivo PK measurement confirmed the advantages of the NP formulation versus Taxol. The area-under-the-curve (AUC) for 48 h for Vitamin E TPGS emulsified PLGA NP formulation of paclitaxel were found 3.0 times larger than that for the Taxol formulation. The sustainable therapeutic time, at which the drug concentration drops below the minimum effective value, for the NP formulation could be 1.67 times longer than that for the Taxol formulation.

Magnetic resonance colonography without bowel cleansing using oral and rectal stool softeners (fecal cracking)--a feasibility study.

The aim of our study was to assess the effect of oral and rectal stool softeners on dark-lumen magnetic resonance (MR) colonography without bowel cleansing. Ten volunteers underwent MR colonography without colonic cleansing. A baseline examination was performed without oral or rectal administration of stool softeners. In a second set, volunteers ingested 60 ml of lactulose 24 h prior to MR examination. In a third examination, water as a rectal enema was replaced by a solution of 0.5%-docusate sodium (DS). A fourth MR examination was performed, in conjunction with both oral administration of lactulose and rectal application of DS. A T1-weighted data set was acquired at scanning times of 0, 5 and 10 min after colonic filling. A fourth data set was acquired 75 s after i.v. injection of contrast agent. Signal intensity of stool was calculated for all colonic segments. Without oral ingestion of lactulose or rectal enema with DS stool signal intensity was high and did not decrease over time. However, lactulose and DS caused a decrease in stool signal intensity. Both substances together led to a decreasing signal intensity of feces. Combination of lactulose and DS provided the lowest signal intensity of stool. Thus, feces could hardly be distinguished from dark rectal enema allowing for the assessment of the colonic wall.

Safety and effectiveness of large-volume enema solutions.

The effectiveness and side effects of three types of enema solutions were compared in healthy subjects. Using a repeated-measures, double-blind design, the three different enemas (soapsuds, tap water, and polyethylene glycol-electrolyte solution) were given at 1-week intervals to 24 healthy volunteers. Soapsuds and tap water enemas produced significantly greater returns than polyethylene glycol electrolyte solution (PEG-ES) and were also more uncomfortable. Rectal biopsies showed surface epithelium loss after soapsuds and tap water but not after PEG-ES enemas. Before recommending changes in nursing practice, further research is needed to determine the mechanism for the surface epithelium damage and to determine if this damage produces a stronger defecation stimulus and discomfort.

New surface-active polymers for ophthalmic formulations: evaluation of ocular tolerance.

Two n-octenylsuccinate starch (AS) types of unknown molecular weights were assessed for ocular tolerance. Irritation potential of different solutions (containing 2 and 15% (w/w) AS) and AS stabilized emulsions (containing 15% (w/w) AS) was evaluated in vivo in rabbit eyes, using a confocal laser scanning microscope, and in vitro on treated excised pig corneas by light microscopy of histological cross sections. Both AS types were previously characterized by viscosity, osmolality and surface tension measurements. All tested solutions and emulsions showed good eye tolerance regardless of concentration and emulsifying properties suggesting AS to be a good alternative to commonly used solubilizing or emulsifying agents in ophthalmic formulations.

In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam.

The impact of the surface-active formulation ingredients Cremophor EL, Tween 80 and Solutol HS 15 on the intrinsic clearance (Clint) of midazolam (MDZ) was investigated in rat hepatocytes and microsomes. In rat hepatocytes with 0.003%, 0.03% and 0.3% (w/v) Solutol HS 15 already present in the incubation medium, the Clint was significantly reduced in a dose-dependent manner by about 25%, 30% and 50%, respectively. In the presence of Cremophor EL and Tween 80 a significant reduction in Clint by about 30% and 25%, respectively, was observed at 0.03% surfactant concentration. At 0.3% of Cremophor EL and Tween 80, Clint was reduced by about 50% and 20%, respectively. A reduction in Clint was also observed in experiments with rat liver microsomes. At surfactant concentrations up to 0.03%, cytotoxicity assays (lactate dehydrogenase release, adenosine triphosphate content) as well as light microscope investigations did not reveal any cytotoxic impact of the surfactants on the hepatocyte monolayer. A potential interaction of the surfactants with biological membranes was determined using phosphatidylcholine-cholesterol liposomes loaded with self-quenching concentrations of carboxyfluorescein. No marked release of carboxyfluorescein from the liposomes (that would be an indication for a surfactant-dependent disruption of membrane integrity) was observed up to concentrations of 0.03% of the different surfactants. It is concluded that cytochrome P450 3A mediated metabolism of MDZ seems to be prevented by all surfactants at concentrations above 0.03%. In our experiments the surfactants did not show toxic effects at concentrations that resulted in a decreased Clint of MDZ. Thus, a direct inhibition of the metabolizing enzymes, a molecular interaction with the microsomes as well as an alteration of membrane properties that did not yet result in a release of LDH have to be taken into consideration as reasons for the observed changes in the metabolism of MDZ.

[Allergic reaction against an emulsifier, HCO-60, contained in multamin and enocitabine].

We report two cases of an allergic reaction to HCO-60, which is used as an emulsifien for Multamin and enocitabine. A 55-year-old woman with M 4 Eo developed a high fever, urticaria and erythema after induction chemotherapy. After stopping the administration of Multamin, her fever and eruptions subsided. A 51-year-old woman with L 2 developed erythema and hypotension 30 minutes after the third administration of Multamin. When the patient was given enocitabine, she developed anaphylactic shock. During chemotherapy in patients with leukemia, it is important to distinguish the allergic reaction against Multamin-containing HCO-60 from infection and allergies to other drugs.