Compatibility Assessment of Novel Orodispersible Film Vehicle for Personalized Medicine with Selected Active Pharmaceutical Ingredients.

Orodispersible films (ODFs) are solid pharmaceutical forms for rapid local or systemic release of active ingredients. They are formed by a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity. In this paper, we describe the compatibility and disintegration times of compounded ODFs using OrPhylloTM, a new ready-to-use-vehicle, and APIs from different pharmacological classes, such as 5-hydroxytryptophan (5-HTP) 50 mg, bromopride 5 mg, coenzyme Q10 20 mg, melatonin 3 mg, resveratrol 5 mg, tadalafil 10 mg, vitamin B12 1 mg, or vitamin D3 2000 UI. ODFs were compounded and, subsequently, the samples were assayed using HPLC at initial (t = 0), 7 days (t = 7), 14 days (t = 14), 30 days (t = 30), 60 days (t = 60), 90 days (t = 90), 120 days (t = 120), 150 days (t = 150), and 180 days (t = 180) after compounding. Given the percentage of recovery of the APIs within the films, the beyond-use date of the final products (API + vehicle) was at least 90 days for vitamin D3, 150 days for bromopride and 5-HTP, and 180 days for coenzyme Q10, tadalafil, vitamin B12, resveratrol, and melatonin, when stored at room temperature. The average disintegration time was 46.22 s. This suggests that the OrPhylloTM vehicle is suitable for compounding ODFs with APIs from different pharmacological classes, with good compatibility and fast disintegration.

Chia oil prevents chemical and immune-mediated inflammatory responses in mice: Evidence for the underlying mechanisms.

Chia (Salvia hispanica L.) is an herbaceous plant used as omega-3 polyunsaturated fatty acid (ω-3 PUFA) source that presents a range of beneficial effects on human health. Herein, it was used a chia oil containing over than 62% of α-linolenic acid (ALA), a compound widely related to anti-inflammatory actions. Chia oil effect was tested using paw edema and mechanical hyperalgesia induced by carrageenan, and ear edema induced by croton oil, histamine, and capsaicin. Croton oil was used in both preventive and therapeutic treatment schedules of chia oil while histamine and capsaicin were used only in preventive treatment schedule. Chia oil mechanism of action was investigated using nociception and paw edema response induced by intraplantar injection of acidified saline (ASIC activator), PGE2 (prostaglandin pathway), cinnamaldehyde (TRPA1 activator), bradykinin (BK pathway), menthol (TRPM8 activator), and capsaicin (TRPV1 activator). Further, RT-PCR for inflammatory mediators (TRPA1, NF-κB, PPAR-γ, COX-2, IL-6, TNF, FPR2, FAAH, MAGL, and IL-12A) induced by carrageenan, NLRP3 inflammasome activation, and the cell viability were then accessed. Later, chia oil actions were evaluated in the experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Chia oil showed anti-edematogenic and anti-hyperalgesic effects when administered 1 h before pro-inflammatory stimulus - particularly carrageenan and croton oil. Moreover, chia oil upregulated the mRNA levels of COX-2 and formyl peptide receptor 2 (FPR2) while reduced IL-6 expression in the spinal cord of mice submitted to i.pl. injection of carrageenan. Interestingly, chia oil mediates antinociceptive effects in mice decreasing the nociceptive response induced by acidified saline, PGE2, and cinnamaldehyde, but not by bradykinin, menthol, and capsaicin. On the EAE model, chia oil preventively administered attenuated EAE-induced motor deficits and mechanical hyperalgesia in mice, suggesting a valuable effect of chia oil supplementation in regulating inflammatory responses and some immune functions during immune-mediated inflammatory disorders (IMID). Nonetheless, additional reports will need to assess the effect of chia oil in well-controlled clinical trials performed in MS patients.

Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor.

Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100-200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a ß-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.

Preparation, Characterization and In Vivo Biocompatibility Studies of Cotton Cellulose Nanofibers.

Cellulose nanofibers have mechanical properties that make them very attractive in a myriad of fields such as biomedicine, tissue engineering, biosensors, cosmetics and food packet products. To evaluate the potential health risks of airborne cellulose nanofibers, the cellulose nanofiber was prepared and characterized and then its pulmonary potential toxicity to a mouse model was studied. Cellulose nanofiber has been prepared by acid hydrolysis of cotton cellulose and characterized by transmission electron microscopy, zeta potential and X-ray diffraction analysis. Then, using a short-term inhalation test, the pulmonary biocompatibility of cotton cellulose nanofibers at different concentrations (0.5 mg/mL, 1 mg/mL and 2 mg/mL) were evaluated. Transmission electron images showed needle-shaped particle with a diameter of about 6-18 nm and a length of 85-225 µm. Zeta potential was -25.3±7.80 mV and the X-ray diffraction patterns indicate that cotton cellulose nanofiber has pure structural characteristics. The In Vivo results revealed that the exposure to cotton cellulose nanofiber did not alter the number of inflammatory cells or cytokine secretion by lung cells (p > 0.05). The results demonstrate that the cotton cellulose nanofiber is biocompatible and it is an environment-friendly nanomaterial with promise in various industrial sectors.

Citral Inhibits the Inflammatory Response and Hyperalgesia in Mice: The Role of TLR4, TLR2/Dectin-1, and CB2 Cannabinoid Receptor/ATP-Sensitive K+ Channel Pathways.

Citral ((2E)-3,7-dimethylocta-2,6-dienal), a bioactive component of lemongrass, inhibits oxidant activity, nuclear factor kappa B (NF-κB) activation, and cyclooxygenase-2 (COX-2) expression, even as it activates peroxisome proliferator-activated receptor (PPAR)-α and γ. Additionally, citral produces long-lasting inhibition of transient receptor potential (TRP) channels that are found in sensory neurons, such as TRPV1-3 and TRPM8, while it transiently blocks TRPV4 and TRPA1. Here, the effect of citral in experimental models of acute inflammation and hyperalgesia in mice, and the underlying citral mechanisms of action were investigated. ADMET properties and molecular targets were predicted using the online server. The immunomodulatory and antihyperalgesic effects of citral were evaluated, using mechanical and thermal stimuli, at different time-points on carrageenan, lipopolysaccharides (LPS), and zymosan-induced paw edema and hyperalgesia in mice. ADMET analysis ensures that the citral has not violated Lipinski's rule of five, indicating its safety consumption, and molecular target prediction software identified that citral is a potential fatty acid amide hydrolase (FAAH) inhibitor. Oral treatment with citral (50-300 mg/kg) significantly inhibited carrageenan-induced paw edema and thermal allodynia. Furthermore, citral modulated the inflammation induced by LPS and zymosan, toll-like receptor (TLR) 4, and TLR2/dectin-1 ligands, respectively. Moreover, pretreatment with cannabinoid receptor type 2 (CB2R) antagonists and ATP-sensitive K+ channel inhibitor, but not with a cannabinoid receptor type 1 (CB1R) antagonist, significantly reversed the anti-inflammatory effect of citral. Intriguingly, citral did not cause any relevant action in the central nervous system, and it was safe when assessed in a 14 day toxicity assay in male mice. Therefore, citral constitutes a promising, innovative, and safe molecule for the management of immunoinflammatory conditions and pain states.

Permeation Efficacy of a Transdermal Vehicle with Steroidal Hormones and Nonsteroidal Anti-inflammatory Agents as Model Drugs.

BACKGROUND: Transdermal delivery is an alternative route for the administration of drugs. However, it requires the development of vehicles that allow the drugs to cross the layers of the skin and reach the systemic circulation. OBJECTIVE: In this study, a new transdermal vehicle was evaluated using progesterone, estradiol, estradiol + estriol (Biest) and ketoprofen administered as model drugs. METHODS: To evaluate the ex vivo permeation of the drugs, the Franz vertical diffusion cell with human skin was used. RESULTS: After 24 h, the vehicle was able to deliver 18.32 µg/cm2 of progesterone and 92.07 µg/cm2 of ketoprofen through the skin to the receptor medium. The permeation percentages were 91%, 78.8%, 48.5%, 73.2%, and 63.6%, respectively, for estradiol, estradiol (Biest), estriol (Biest), progesterone and ketoprofen. For all drugs, sufficient amounts were delivered to achieve a systemic effect, and it was also possible to decrease the amount of emulsion applied. CONCLUSION: Thus, the vehicle demonstrated a high performance and the possibility of it being used for drugs that present difficulties in regards to administration by the transdermal route.

Insights on the transport of tamoxifen by gold nanoparticles for MCF-7 breast cancer cells based on SERS spectroscopy.

Gold nanoparticles (AuNP) were synthesized and modified with anti-folate receptor antibody (AB), folic acid (FA), crystal violet (CV), poly (ethyleneglycol) methyl ether thiol and the antineoplastic drug tamoxifen (TAM). Such a preparation was incubated in vitro with MCF-7 human breast cancer cells, showing a decrease in the TAM dosage for the reduction of cell viability. The adsorption of TAM on gold surface was investigated by surface-enhanced Raman scattering (SERS) spectroscopy and the assignment based on Density Functional Theory calculations showed that the ether moiety was involved in the interactions with the metal. Such a chemical affinity was correlated with the carrying of TAM in the biological media. CV was included in the preparation as a molecular probe for SERS spectroscopy, whose signal was monitored to analyse the efficiency of the modified AuNP in the target of neoplastic cells. The results showed AB, FA and TAM components had complementary roles in the cell recognition and, therefore, in the efficiency of the drug carrier nanosystem.

Biosynthesis of silver nanoparticles using Caesalpinia ferrea (Tul.) Martius extract: physicochemical characterization, antifungal activity and cytotoxicity.

BACKGROUND: Green synthesis is an ecological technique for the production of well characterized metallic nanoparticles using plants. This study investigated the synthesis of silver nanoparticles (AgNPs) using a Caesalpinia ferrea seed extract as a reducing agent. METHODS: The formation of AgNPs was identified by instrumental analysis, including ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) of the AgNPs, and surface-enhanced Raman scattering (SERS) spectra of rhodamine-6G (R6G). We studied the physicochemical characterization of AgNPs, evaluated them as an antifungal agent against Candida albicans, Candida kruzei, Candida glabrata and Candida guilliermondii, and estimated their minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. Lastly, this study evaluated the cytotoxicity of the AgNPs in murine L929 fibroblasts cells using an MTT assay. RESULTS: The UV-Vis spectroscopy, SERS, SEM and XRD results confirmed the rapid formation of spheroidal 30-50 nm AgNPs. The MIC and MFC values indicated the antifungal potential of AgNPs against most of the fungi studied and high cell viability in murine L929 fibroblasts. In addition, this study demonstrated that C. ferrea seed extracts may be used for the green synthesis of AgNPs at room temperature for the treatment of candidiasis.

Taxifolin: Evaluation Through Ex vivo Permeations on Human Skin and Porcine Vaginal Mucosa.

BACKGROUND: Taxifolin (TAX) is a flavonoid that has numerous pharmacological properties, including an antioxidant ability superior to that of other flavonoids due to its particular structure. Nevertheless, it has low oral bioavailability, which limits its therapeutic application. In this context, potentially important approaches for systemic drug delivery could be by alternative routes such as skin and vaginal mucosa, once both routes have a variety of advantages compared with the oral route, including the ability to bypass both first-pass hepatic metabolism and the consequent degradation in the gastrointestinal tract. Vaginal delivery could also account for a local effect, or an effect on circumvent microregion. OBJECTIVE: The major objective of this study was to develop and validate a high-performance liquid chromatography (HPLC) method for the determination of TAX in a semisolid dosage forms and then to evaluate ex vivo permeations across porcine vaginal mucosa and human skin. METHODS: TAX was incorporated into an oil-in-water emulsion developed previously by our group. Method for quantification was developed and validated using HPLC. Permeation through human skin and vaginal porcine mucosa were conducted in Franz-type cells. RESULTS: The method was precise (CV < 5%), accurate (recovery between 98% and 102%), linear (R2> 0.99), specific, and robust. Permeation experiments through porcine vaginal mucosa and human skin presented permeated percentages equal to 87.43% and 48.09% (per dose), respectively. CONCLUSION: The results suggest that, in the matrixes studied, TAX may be able to exert its biological activities systemically when applied by these routes. Furthermore, it exhibits greater permeability potential when administered by intravaginal route.

In Vitro Antifungal Activity of Hexahydropyrimidine Derivatives against the Causative Agents of Dermatomycosis.

Nitrogenated heterocyclic compounds are present in both natural and synthetic drugs, and hexahydropyrimidine derivatives may prove to be efficient in treating dermatomycosis causing fungi. This study evaluated the antifungal activity of four hexahydropyrimidine derivatives against the dermatomycosis causing fungi. These derivatives were synthesized, characterized, and assessed in terms of their activity against Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Fusarium oxysporum, and Epidermophyton floccosum between concentrations 7.8 and 1,000 µg mL-1. Scanning electron micrographs were assessed for the active derivatives and reference drugs, and these micrographs revealed that new agents cause morphological changes in fungi. The derivatives HHP1, HHP3, and HHP4 revealed poor activity against the four fungal strains (MICs range 500-1000 µg mL-1). Compound HHP3 was found to be the best potential antifungal agent among those tested and was the most effective among all the active derivatives that caused morphological changes in the susceptible strains.

Effect of Multi-walled Carbon Nanotubes on Metabolism and Morphology of Filamentous Green Microalgae.

Multi-walled carbon nanotubes (MWCNTs) have potential applications in the industrial, agricultural, pharmaceutical, medical, and environmental remediation fields. However, many uncertainties exist regarding the environmental implications of engineered nanomaterials. This study examined the effect of the MWCNTs on metabolic status and morphology of filamentous green microalgae Klebsormidium flaccidum. Appropriate concentrations of MWCNT (1, 50, and 100 µg mL-1) were added to a microalgal culture in the exponential growth phase and incubated for 24, 48, 72, and 96 h. Exposure to MWCNT led to reductions in algal growth after 48 h and decreased on cell viability for all experimental endpoints except for 1 µg mL-1 at 24 h and 100 µg mL-1 after 72 h. At 100 µg mL-1, MWCNTs induced reactive oxygen species (ROS) production and had an effect on intracellular adenosine triphosphate (ATP) content depending on concentration and time. No photosynthetic activity variation was observed. Observations by scanning transmission electron microscopy showed cell damage. In conclusion, we have demonstrated that exposure to MWCNTs affects cell metabolism and microalgal cell morphology. To our best knowledge, this is the first case in which MWCNTs exhibit adverse effects on filamentous green microalgae K. flaccidum. These results contribute to elucidate the mechanism of MWCNT nanotoxicity in the bioindicator organism of terrestrial and freshwater habitats.

Efficient delivery of DNA into bovine preimplantation embryos by multiwall carbon nanotubes.

The pellucid zone (PZ) is a protective embryonic cells barrier against chemical, physical or biological substances. This put, usual transfection methods are not efficient for mammal oocytes and embryos as they are exclusively for somatic cells. Carbon nanotubes have emerged as a new method for gene delivery, and they can be an alternative for embryos transfection, however its ability to cross the PZ and mediated gene transfer is unknown. Our data confirm that multiwall carbon nanotubes (MWNTs) can cross the PZ and delivery of pDNA into in vitro-fertilized bovine embryos. The degeneration rate and the expression of genes associated to cell viability were not affected in embryos exposed to MWNTs. Those embryos, however, had lower cell number and higher apoptotic cell index, but this did not impair the embryonic development. This study shows the potential utility of the MWNT for the development of new method for delivery of DNA into bovine embryos.

Antioxidant activity and potential photoprotective from amazon native flora extracts.

Plant species are sources of active compounds that can fight and/or prevent damage caused by reactive oxygen species, which enables the development of natural products that can help to prevent premature aging caused by exposure to solar radiation. This study assessed the antioxidant and photoprotective activities of six dried extracts of plants from the Brazilian Amazon biome. Plant extracts were prepared in 70% (v/v) ethanol by dynamic maceration for 72h in the dark, and then filtered, concentrated and lyophilized. The extracts were subjected to a phytochemical screening. The antioxidant activity was measured using a 2,2-diphenyl-1-picrylhydrazyl assay and the photoprotection assay was performed using the diffuse transmittance technique. The data obtained from the antioxidant activity assay was evaluated by Student's t-test for independent samples, with the aid of Statistical Package for Social Sciences v.14.0 for Windows software. The flavonoids represent a special metabolites class present in all analyzed extracts. The antioxidant activity (µgmL(-1)) decreased in the following order: Aniba canelilla (1.80±0.16), Brosimum acutifolium (2.84±0.38), Dalbergia monetaria (5.46±0.17) or Caesalpinia pyramidalis (6.45±1.18), Arrabidaea chica (15.35±0.86), and Aspidosperma nitidum (99.14±2.3). Only D. monetaria showed a considerable sun protection factor allowing for labeling (6.0±0.3). The D. monetaria extract was considered the most promising sample because it had optimal antioxidant and photoprotective activities against solar radiation, considering the limit established by regulatory agencies. These extracts with antioxidant potential can be used in photoprotective formulations, providing synergistic photoprotective effect or elevating the adeed value of the product. Additionally, these formulations are attractive to a population who searchs for products made with natural ingredients.

Biocompatibility assessment of fibrous nanomaterials in mammalian embryos.

Currently there is a growing interest in the use of nanotechnology in reproductive medicine and reproductive biology. However, their toxic effects on mammalian embryos remain poorly understood. In this work, we evaluate the biocompatibility of two fibrous nanomaterials (NMs): cotton cellulose nanofibers (CNF) and carboxylated multiwalled carbon nanotubes (MWCNT-COOH), by performing an investigation of the embryonic development, gene expression (biomarkers focused on cell stress, apoptosis and totipotency) and in situ apoptosis in bovine embryos. Exposure to NMs did not interfere in preimplantation development or in the incidence of apoptosis in the bovine embryo, but they did affect the gene expression. The results presented are important for an understanding of the toxicity of cotton CNF and MWCNT-COOH on mammalian embryos. To our knowledge, we report the first evaluation of biocompatibility between these NMs on preimplantation embryos, which may open a new window for reproductive biomedical applications.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

Interferometry as a tool for evaluating effects of antimicrobial doses on Mycobacterium bovis growth.

Interferometry was used together with the conventional microplate resazurin assay to evaluate the antimycobacterial properties of essential oil (EO) from fruits of Pterodon emarginatus and also of rifampicin against Mycobacterium bovis. The aim of this work is not only to investigate the potential antimycobacterial activity of this EO, but also to test the interferometric method in comparison with the conventional one. The Minimum Inhibitory Concentration (MIC) values of EO (625 µg/mL) and rifampicin (4 ng/mL) were firstly identified with the microplate method. These values were used as parameters in Drug Susceptibility Tests (DST) with interferometry. The interferometry confirmed the MIC value of EO identified with microplate and revealed a bacteriostatic behavior for this concentration. At 2500 µg/mL interferometry revealed bactericidal activity of the EO. Mycobacterial growth was detected with interferometry at 4 ng/mL of rifampicin and even at higher concentrations. One important difference is that the interferometric method preserves the sample, so that after weeks of quantitative observation, the sample can be used to evaluate the bactericidal activity of the tested drug.

Direct and indirect toxic effects of cotton-derived cellulose nanofibres on filamentous green algae.

Recently, cellulose nanofibers (CNFs) have attracted considerable attention as natural, abundant polymers with excellent mechanical properties and biodegradability. CNFs provide a new materials platform for the sustainable production of high-performance nano-enable products for various applications. Given the increasing rates of CNF production, the potential for their release to the environment and the subsequent impact on ecosystem is becoming an increasing concern that needs to be addressed. Here, we used the Klebsormidium flaccidum as a bioindicator organism of terrestrial and freshwater habitats pollution using a battery of biomarkers. Our results show that cotton CNFs inhibit the proliferation of algae and induce morphological changes in them. The two main toxicity mechanisms induced by cotton CNFs are: (i) a direct contact of CNFs with the cell wall and cellular membrane and (ii) an indirect effect through the generation of reactive oxygen species (ROS).

Conjugated linoleic acid-enriched butter improved memory and up-regulated phospholipase A2 encoding-genes in rat brain tissue.

Reduced phospholipase A2 (PLA2) activity has been reported in blood cells and in postmortem brains of patients with Alzheimer disease (AD), and there is evidence that conjugated linoleic acid (CLA) modulates the activity of PLA2 groups in non-brain tissues. As CLA isomers were shown to be actively incorporated and metabolized in the brains of rats, we hypothesized that feeding a diet naturally enriched in CLA would affect the activity and expression of Pla 2 -encoding genes in rat brain tissue, with possible implications for memory. To test this hypothesis, Wistar rats were trained for the inhibitory avoidance task and fed a commercial diet (control) or experimental diets containing either low CLA- or CLA-enriched butter for 4 weeks. After this period, the rats were tested for memory retrieval and killed for tissue collection. Hippocampal expression of 19 Pla 2 genes was evaluated by qPCR, and activities of PLA2 groups (cPLA2, iPLA2, and sPLA2) were determined by radioenzymatic assay. Rats fed the high CLA diet had increased hippocampal mRNA levels for specific PLA2 isoforms (iPla 2 g6γ; cPla 2 g4a, sPla 2 g3, sPla 2 g1b, and sPla 2 g12a) and higher enzymatic activity of all PLA2 groups as compared to those fed the control and the low CLA diet. The increment in PLA2 activities correlated significantly with memory enhancement, as assessed by increased latency in the step-down inhibitory avoidance task after 4 weeks of treatment (rs = 0.69 for iPLA2, P < 0.001; rs = 0.81 for cPLA2, P < 0.001; and rs = 0.69 for sPLA2, P < 0.001). In face of the previous reports showing reduced PLA2 activity in AD brains, the present findings suggest that dairy products enriched in cis-9, trans-11 CLA may be useful in the treatment of this disease.

Synthesis of conjugated bile acids/azastilbenes as potential antioxidant and photoprotective agents.

A series of 14 bile acids/azastilbenes conjugates (1a-g and 2a-g) was prepared through the condensation of bile amides (1 and 2) and aromatic aldehydes. The newly synthesized conjugates were evaluated in vitro for their antioxidant and photoprotective activities. Six compounds (1, 1a, 1b, 2, 2a and 2b) showed promising antioxidant activity with IC50 values of 19.60-31.83 µg mL(-1). The synthesized compounds presented a varied photoprotection profile, with the SPF ranging from 2 to 9. Among the 16 compounds tested for the protection against UVB sunrays, 3 compounds (2c, 2e and 2g) presented more significant protection than resveratrol and the free azastilbene 3; while the UVAPF increased from 2 in resveratrol and 5 in 3 to 5-11 in the majority of the conjugates.

Size-dependent ecotoxicity of barium titanate particles: the case of Chlorella vulgaris green algae.

Studies have been demonstrating that smaller particles can lead to unexpected and diverse ecotoxicological effects when compared to those caused by the bulk material. In this study, the chemical composition, size and shape, state of dispersion, and surface's charge, area and physicochemistry of micro (BT MP) and nano barium titanate (BT NP) were determined. Green algae Chlorella vulgaris grown in Bold's Basal (BB) medium or Seine River water (SRW) was used as biological indicator to assess their aquatic toxicology. Responses such as growth inhibition, cell viability, superoxide dismutase (SOD) activity, adenosine-5-triphosphate (ATP) content and photosynthetic activity were evaluated. Tetragonal BT (~170 nm, 3.24 m(2) g(-1) surface area) and cubic BT (~60 nm, 16.60 m(2) g(-1)) particles were negative, poorly dispersed, and readily aggregated. BT has a statistically significant effect on C. vulgaris growth since the lower concentration tested (1 ppm), what seems to be mediated by induced oxidative stress caused by the particles (increased SOD activity and decreased photosynthetic efficiency and intracellular ATP content). The toxic effects were more pronounced when the algae was grown in SRW. Size does not seem to be an issue influencing the toxicity in BT particles toxicity since micro- and nano-particles produced significant effects on algae growth.