Impact of adherence goal awareness intervention on PDC in various settings: Does awareness help modify medication-taking behavior?

Background: Interventions to improve medication adherence in chronic conditions have shown limited success or sustainability. Previous data revealed that phone calls to patients regarding adherence goal awareness resulted in significant improvement in proportion of days covered (PDC). Objectives: The objective of this study was to explore specific pharmacist adherence interventions via phone in various practice settings. Methods: A prospective, randomized controlled study was conducted with patients who belonged to university-associated health care settings [ambulatory care, chain store, small health plan, and federally qualified health center (FQHC)]. At each site, patients with at least one chronic medication and a calculated PDC < 0.80 were randomized into control (n=115) and intervention (n=126) groups. Control groups (C) received usual pharmacy communication while intervention groups (X) were specifically called by a pharmacist to be informed of PDC goals and their commitment to adherence. PDC values were calculated 3 to 12 months for both groups the time of intervention, then compared with each patient's respective baseline/pre-PDC. Results: Data from a total of 241 patients were pooled to examine change in PDC. There was no significant difference between groups in baseline criteria or PDC. Comparing within groups, there were significant correlations between Pre- and Post-PDCs for the intervention group (X = 0.32 p < 0.05) alone. There were significant improvements from initial PDC to those calculated at the time of Post-intervention PDC within both groups, (C = 0.18 ± 0.28 p < 0.05) and (X = 0.16 ± 0.24, p < 0.05). Approximately 44% of all sampled patients reached their adherence goals (PDC ≥ 0.80) after 3-9 months. Conclusions: Results suggested that patient adherence behavior may improve after any call made by pharmacy staff. This communication and attention from the pharmacy may be enough for patients to consider their medication-taking habits without the need for discussing specific goals and importance of adherence.

Comprehensive Database of Carotenoid Contents in Ibero-American Foods. A Valuable Tool in the Context of Functional Foods and the Establishment of Recommended Intakes of Bioactives.

Foods that are commonly consumed in the diet are considered to provide more than 40 different carotenoids. However, the content in carotenoids varies considerably in both qualitative and quantitative terms as a consequence of different genotypes, climatic conditions of the production area, and agronomic factors, among others. In this paper, analytical data, obtained by HPLC or UHPLC, of carotenoids in fruits and vegetables produced in Ibero-America have been compiled from peer-reviewed journals, organized in food categories, and documented in relation to the sampling and analytical quality system used. In addition to common products of the diet of the Ibero-American countries, other wild or little used fruit and vegetables have been included with the aim of contributing to promote and to value species and local varieties. The importance of the commodities containing carotenoids in food, health, agriculture, and biodiversity, and the need of their preservation, was evidenced in this work namely by the large differences in carotenoid content related to the locals of production and varieties, and the high levels of carotenoids in native fruits and vegetables. The contribution of these compounds to meet the needs of vitamin A as well as the necessity of establishing recommendation for the daily intakes of theses bioactive compounds were also discussed.

Thermal adaptation strategies of the extremophile bacterium Thermus filiformis based on multi-omics analysis.

Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot spring in New Zealand. The experimental study of the mechanisms of thermal adaptation is important to unveil response strategies of the microorganism to stress. In this study, the main pathways involved on T. filiformis thermoadaptation, as well as, thermozymes with potential biotechnological applications were revealed based on omics approaches. The strategy adopted in this study disclosed that pathways related to the carbohydrate metabolism were affected in response to thermoadaptation. High temperatures triggered oxidative stress, leading to repression of genes involved in glycolysis and the tricarboxylic acid cycle. During heat stress, the glucose metabolism occurred predominantly via the pentose phosphate pathway instead of the glycolysis pathway. Other processes, such as protein degradation, stringent response, and duplication of aminoacyl-tRNA synthetases, were also related to T. filiformis thermoadaptation. The heat-shock response influenced the carotenoid profile of T. filiformis, favoring the synthesis of thermozeaxanthins and thermobiszeaxanthins, which are related to membrane stabilization at high temperatures. Furthermore, antioxidant enzymes correlated with free radical scavenging, including superoxide dismutase, catalase and peroxidase, and metabolites, such as oxaloacetate and α-ketoglutarate, were accumulated at 77 °C.

Oxidative stability of yogurt with added lutein dye.

This study evaluated the effect of adding lutein dye on the oxidative stability of yogurt during 35 d of refrigerated storage, in the presence and absence of light. Yogurts manufactured without and with the equivalent of 1.5mg of lutein in 120 g of the final product were characterized for their total carotenoid and riboflavin contents, and the behaviors of both riboflavin and lutein were monitored during storage. A decrease in riboflavin content occurred, with concurrent appearance of its derived-oxidation products in the yogurts without added lutein and exposed to light during storage. The yogurts with added lutein dye showed constant lutein and riboflavin contents throughout storage both for the samples stored under light and for those stored in the dark. Yogurts (120 g) with the addition of 0.5, 1.5, and 2.5mg of lutein dye were evaluated for their sensory acceptance, and the statistical analysis showed no differences between the samples for the attributes of aroma and flavor. These results indicate that the added lutein remained stable throughout the storage period and conferred protection for the riboflavin against photooxidation, preserving the quality of the yogurts.

Effects of lutein and chlorophyll b on GSH depletion and DNA damage induced by cisplatin in vivo.

Recent studies have proposed the use of low concentrations of phytochemicals and combinations of phytochemicals in chemoprevention to reduce cytotoxicity and simulate normal ingestion through diet. The purpose of the present study was to evaluate whether the DNA damage, chromosome instability, and oxidative stress induced by cisplatin (cDDP) are modulated by a combination of the natural pigments lutein (LT) and chlorophyll b (CLb). The protective effects observed for synergism between phytochemicals have not been completely investigated. The comet assay and micronucleus test were performed and the catalase activities and glutathione (GSH) concentrations were measured in the peripheral blood, bone marrow, liver, and kidney cells of mice. The comet assay and micronucleus test results revealed that the pigments LT and CLb were not genotoxic or mutagenic and that the pigments presented antigenotoxic and antimutagenic effects in the different cell types evaluated. This protective effect is likely related to antioxidant properties in peripheral blood cells through the prevention of cDDP-induced GSH depletion. Altogether our results show that the combination of LT and CLb, which are both usually present in the same foods, such as leafy green vegetables, can be used safely.

Luminosity-independent measurement of the proton-proton total cross section at √s=8 TeV.

The TOTEM collaboration has measured the proton-proton total cross section at √s=8 TeV using a luminosity-independent method. In LHC fills with dedicated beam optics, the Roman pots have been inserted very close to the beam allowing the detection of ~90% of the nuclear elastic scattering events. Simultaneously the inelastic scattering rate has been measured by the T1 and T2 telescopes. By applying the optical theorem, the total proton-proton cross section of (101.7±2.9) mb has been determined, well in agreement with the extrapolation from lower energies. This method also allows one to derive the luminosity-independent elastic and inelastic cross sections: σ(el)=(27.1±1.4) mb; σ(inel)=(74.7±1.7) mb.

The characterization of a thermostable and cambialistic superoxide dismutase from Thermus filiformis.

UNLABELLED: The superoxide dismutase (TfSOD) gene from the extremely thermophilic bacterium Thermus filiformis was cloned and expressed at high levels in mesophilic host. The purified enzyme displayed approximately 25 kDa band in the SDS-PAGE, which was further confirmed as TfSOD by mass spectrometry. The TfSOD was characterized as a cambialistic enzyme once it had enzymatic activity with either manganese or iron as cofactor. TfSOD showed thermostability at 65, 70 and 80°C. The amount of enzyme required to inhibit 50% of pyrogallol autoxidation was 0·41, 0·56 and 13·73 mg at 65, 70 and 80°C, respectively. According to the circular dichroism (CD) spectra data, the secondary structure was progressively lost after increasing the temperature above 70°C. The 3-dimensional model of TfSOD with the predicted cofactor binding corroborated with functional and CD analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: This manuscript describes the expression and characterization of a superoxide dismutase (SOD) from Thermus filiformis with thermophilic and cambialistic characteristics. The SODs are among the most potent antioxidants known in nature, and their stability and pharmacokinetics can vary widely in accordance to their biological source. Although the currently clinical research work has been focused on human and bovine SODs, alternative sources may become more biotechnological attractive in the near future. Our study brings new insights for the research field of antioxidant enzymes with potential application on pharmaceutical, cosmetics and food formulations.

Double diffractive cross-section measurement in the forward region at the LHC.

The first double diffractive cross-section measurement in the very forward region has been carried out by the TOTEM experiment at the LHC with a center-of-mass energy of sqrt[s]=7 TeV. By utilizing the very forward TOTEM tracking detectors T1 and T2, which extend up to |η|=6.5, a clean sample of double diffractive pp events was extracted. From these events, we determined the cross section σDD=(116±25) µb for events where both diffractive systems have 4.7<|η|min<6.5.

Effect of natural pigments on the oxidative stability of sausages stored under refrigeration.

The objective was to use natural pigments to replace sodium erythorbate (NaEry), a synthetic compound used as an antioxidant in sausage formulations, and to evaluate the oxidative stability of the samples. Six assays were prepared in which sodium erythorbate (ERY) at 0.05 g/100 g was substituted by norbixin (NOR), lycopene (LYC), zeaxanthin (ZEA), beta-carotene (CAR) or dextrose (used as a control (CON)). Physical, chemical, color, texture and sensory parameters were measured on the first day and after 45 days of storage at 4 degrees C. All pigments used in the sausage formulations were able to maintain the oxidative stability of the sausages (MDA equivalents <0.38 mg/kg). Zeaxanthin and norbixin were the most efficient antioxidants of those tested. This antioxidant effect might be associated with the intermediate polarities of these two compounds, which would allow them to concentrate in the membrane lipids or emulsion interface, where lipid oxidation is most prevalent. Other volatile secondary products of oxidation besides MDA should be evaluated in further studies involving natural pigments and sensory oxidative stability.

Carotenoid composition of jackfruit (Artocarpus heterophyllus), determined by HPLC-PDA-MS/MS.

Carotenoids are pigments responsible for the yellow-reddish color of many foods and are related to important functions and physiological actions, preventing several chronic-degenerative diseases. The objective of this study was to confirm the carotenoid composition of jackfruit by high-performance liquid chromatography connected to photodiode array and mass spectrometry detectors (HPLC-PDA-MS/MS). The main carotenoids were all-trans-lutein (24-44%), all-trans-beta-carotene (24-30%), all-trans-neoxanthin (4-19%), 9-cis-neoxanthin (4-9%) and 9-cis-violaxanthin (4-10%). Either qualitative or quantitative differences, mainly related to the lutein proportion, were found among three batches of jackfruit. Since the fruits from batch A showed significantly lower contents for almost all carotenoids, it also had the lowest total carotenoid content (34.1 microg/100 g) and provitamin A value, whereas the total carotenoid ranged from 129.0 to 150.3 microg/100 g in the other batches. The provitamin A values from batches B and C were 3.3 and 4.3 microg RAE/100 g, respectively. The carotenoid composition of jackfruit was successfully determined, where 14 of the 18 identified carotenoids were reported for first time. Differences among batches may be due to genetic and/or agricultural factors.

Novel method for the determination of added annatto colour in extruded corn snack products.

There is considerable interest in determining the added levels of the natural dye annatto in foods like snack products, particularly because they are mostly consumed by young people. The objective was to use response surface methodology to develop a new method to analyse annatto in extruded snacks. A pretreatment of the samples was necessary, digesting the ground sample with alpha-amylase at room temperature. The pigment was extracted by shaking with ethyl acetate at room temperature, eight extractions being necessary for completion extract the pigment. Lipids were removed by alkaline saponification. Under these conditions, 100% of the bixin was converted into norbixin, which was then quantified by high-performance liquid chromatography. The method had a mean recovery of 97% and a coefficient of variation for duplicate analysis of 1%. Using this method, of the 13 commercial samples analysed, a parmesan cheese-flavoured snack product showed the highest level of dye expressed as norbixin (15.5 mg kg(-1)), whilst other brands of onion-flavoured snack products had the lowest levels (0.7 and 0.4 mg kg(-1), respectively).

Neonatal rat exposure to pyrethroid and organophosphate insecticides: a physiological and biochemical trial of progeny

A manufactured product (Ectoplus R) composed by a cypermethrin (44,7 por cento) and dichlorvos (4,2 por cento) mixture was administered (10mg-day, orally, by gavage) to pregnant rats, during the periods of gestation+lactation, gestation, and lactation. Controlmothers received vehicle aqueous solution during the gestation+lactation period. With the progeny, in the 1-15 post-natal days (PND1-15) there were observed alterations in the periods of occurrence of teeth, hair, unfolding of ears, and in the developmental period for following reflexes: postural, palmar grasp, negative geotaxis, and acoustic startle reflex. After weaning (PND21), there were observed the presence of cypermethrin and dichlorvos in the blood brain and liver, decrease in weight of liver, of cholinesterase activity in the plasma, liver, and brain, and hepatic metabolizing activity of drugs, alterations of levels of gamma glutamyl transferase enzymes, of creatinine, and of potassium in the serum of the animals. In conclusion, neonatal exposure to a formulated mixture of cypermethrin and dichlorvos is inductive to alterations in characteristics that indicate somatic and neuromuscular development of the progeny, and in certain biochemical parameters. The results suggest that enzymatic assessment associated with somatic and neuromotor assessment can be important markers of developmental characteristics in neonatal toxicity by pesticide formulations based on mixtures of insecticides.

Insights into the physiological function of cellular prion protein

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction

Insights into the physiological function of cellular prion protein.

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction.

Laminin-induced PC-12 cell differentiation is inhibited following laser inactivation of cellular prion protein.

Prions, the etiological agents for infectious degenerative encephalopathies, act by inducing structural modifications in the cellular prion protein (PrPc). Recently, we demonstrated that PrPc binds laminin (LN) and that this interaction is important for the neuritogenesis of cultured hippocampal neurons. Here we have used the PC-12 cell model to explore the biological role of LN-PrPc interaction. Antibodies against PrPc inhibit cell adhesion to LN-coated culture plaques. Furthermore, chromophore-assisted laser inactivation of cell surface PrPc perturbs LN-induced differentiation and promotes retraction of mature neurites. These results point out to the importance of PrPc as a cell surface ligand for LN.

Cellular prion protein binds laminin and mediates neuritogenesis.

Laminin (LN) plays a major role in neuronal differentiation, migration and survival. Here, we show that the cellular prion protein (PrPc) is a saturable, specific, high-affinity receptor for LN. The PrPc-LN interaction is involved in the neuritogenesis induced by NGF plus LN in the PC-12 cell line and the binding site resides in a carboxy-terminal decapeptide from the gamma-1 LN chain. Neuritogenesis induced by LN or its gamma-1-derived peptide in primary cultures from rat or either wild type or PrP null mice hippocampal neurons, indicated that PrPc is the main cellular receptor for that particular LN domain. These results point out to the importance of the PrPc-LN interaction for the neuronal plasticity mechanism.

Carotenoids from guava (Psidium guajava l.): isolation and structure elucidation.

Sixteen carotenoids were isolated from the flesh of Brazilian red guavas (Psidium guajava L.). Their structures were established by means of UV-visible, 400 and 500 MHz (1)H NMR, 120 and 125 MHz (13)C NMR, mass, and circular dichroism spectra. The carotenoids were identified as phytofluene, (all-E)-, (9Z)-, (13Z)-, and (15Z)-beta-carotene, (all-E)-gamma-carotene, (all-E)-, (9Z)-, (13Z)-, and (15Z)-lycopene, (all-E,3R)-beta-cryptoxanthin, (all-E, 3R)-rubixanthin, (all-E,3S,5R,8S)-cryptoflavin, (all-E,3R,3'R, 6'R)-lutein, (all-E,3S,5R,6R,3'S,5'R,8'R)-, and (all-E,3S,5R,6R,3'S, 5'R,8'S)-neochrome. Thirteen of the carotenoids identified are reported as guava carotenoids for the first time.

Chromatographic separation of carotenoids.

The carotenoids are extremely reactive and consequently unstable due to their long system of conjugated double bonds. Several precautions, such as protection against light and oxygen, use of low temperature and antioxidants, analysis in the shortest possible time, should be taken during isolation and chromatography. The food samples, preferably fresh, are homogenized and immediately extracted with a suitable organic solvent. Saponification has been employed in order to hydrolyze the carotenoid esters, remove fatty material and destroy chlorophyll. This optional step facilitates subsequent carotenoid separation, identification and quantification. The separation of carotenoids is usually carried out by column chromatography, thin layer chromatography and high performance liquid chromatography, in analytical or preparative scale, on many stationary phases such as silica-gel, alumina, MgO, Ca(OH)2 and reversed-phase material (C18 and C30). The choice of the most suitable chromatographic method depends on the amount of sample, carotenoid composition, resolution, speed and purity required. Examples of carotenoid separation in different stationary phases will be shown and discussed.

Clinical, cytogenetic and toxicological studies in rural workers exposed to pesticides in Botucatu, São Paulo, Brazil.

Pesticides can cause gene mutations and chromosomal aberrations in exposed individuals. We have investigated 24 workers exposed to pesticides. Clinical examinations and cytogenetic and toxicological tests were performed. Ten non-exposed individuals were used as controls. Toxicological dosages of copper, zinc and manganese (metals found in some pesticides), hepatic enzyme dosage (GOT, GPT, AR) and acetylcholinesterase activity were performed in 16 workers and 8 controls. In the exposed workers, the most relevant clinical symptoms were poor digestion with fullness sensation after meals, irritated eyes, headache and fasciculations. The exposed group showed significantly lower manganese dosage and acetylcholinesterase activity, and significantly higher levels of alkaline phosphatase. Cytogenetic studies showed significantly higher chromosomal aberrations in the exposed group compared to the control group. Although the workers used protection against the pesticide's fog, the results revealed that the workers were contaminated with the pesticides. Therefore, the cytogenetic, toxicological studies with clinical examination are necessary for monitoring workers who are exposed to pesticides in any situation.

Complementary hydropathy identifies a cellular prion protein receptor.

Prions, the etiological agents for infectious degenerative encephalopathies, act by entering the cell and inducing conformational changes in PrPC (a normal cell membrane sialoglycoprotein), which result in cell death. A specific cell-surface receptor to mediate PrPC and prion endocytosis has been predicted. Complementary hydropathy let us generate a hypothetical peptide mimicking the receptor binding site. Antibodies raised against this peptide stain the surface of mouse neurons and recognize a 66-kDa membrane protein that binds PrPC both in vitro and in vivo. Furthermore, both the complementary prion peptide and antiserum against it inhibit the toxicity of a prion-derived peptide toward neuronal cells in culture. Such reagents might therefore have therapeutic applications.