Indomethacin-omeprazole as therapeutic hybrids? Salt and co-amorphous systems enhancing physicochemical and pharmacological properties.

Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non-selective non-steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME co-amorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state co-amorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co-amorphous system) showed partial decomposition of OME. The IND:OME co-amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8-fold after 8 h of dissolution) and co-amorphous (2.5-fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (∼5mg/kg) for both IND:OME salt (2.8-fold) and IND:OME co-amorphous system (3.2-fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co-amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME co-amorphous system when compared with crystalline OME.

Effects of a nanoemulsion with Copaifera officinalis oleoresin against monogenean parasites of Colossoma macropomum: A Neotropical Serrasalmidae.

Monogeneans are ectoparasites that may cause losses in production and productivity in the aquaculture of Colossoma macropomum. Chemotherapeutics used in aquaculture usually have major adverse effects on fish; hence, the use of essential oils has been considered advantageous, but these are not soluble in water. Thus, the use of nanostructures to enhance water solubility of compounds and improve bioactivity may be very promising. This study investigated the antiparasitic activity of nanoemulsion prepared with Copaifera officinalis oleoresin (50, 100, 150, 200 and 300 mg/L), against monogenean parasites from the gills of C. macropomum. The particle size distribution and zeta potential suggested that a potentially kinetic stable system was generated. The nanoemulsion from C. officinalis oleoresin achieved high efficacy (100%) at low concentrations (200 and 300 mg/L) after 15 min of exposure. This was the first time that a nanoemulsion was generated from C. officinalis oleoresin using a solvent-free, non-heating and low-energy method. Moreover, this was the first time that an antiparasitic against monogeneans on fish gills, based on nanoemulsion of C. officinalis oleoresin, was tested.

Nanoemulsion from essential oil of Pterodon emarginatus (Fabaceae) shows in vitro efficacy against monogeneans of Colossoma macropomum (Pisces: Serrasalmidae).

Outbreaks of diseases pose a major threat to sustainable aquaculture development worldwide. Application of herbal products to combat parasitic diseases provides an alternative approach for sustainable aquaculture. This study investigated the in vitro antiparasitic effects of an oil-in-water nanoemulsion prepared using the essential oil from Pterodon emarginatus, against monogeneans infesting Colossoma macropomum. Gill arches from C. macropomum (47.6 ± 14.5 g and 13.5 ± 1.4 cm) that were naturally parasitized by Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri were immersed in different dispersions of the P. emarginatus nanoemulsions (0, 50, 100, 200, 400 and 600 mg/L). The major compounds presented in the essential oil of P. emarginatus were ß-elemene, ß-caryophyllene and α-humulene. Characterization of these nanoemulsions showed that they have a small mean droplet size and low polydispersity index, which is concordant with stable systems. In this in vitro trial, the P. emarginatus nanoemulsion concentrations of 100, 200, 400 and 600 mg/L presented 100% helminthic efficacy against monogeneans of the gills of C. macropomum. The highest two concentrations used (400 and 600 mg/L) were seen to immobilize the parasites after only 15 min. Therefore, it would be worthwhile testing these concentrations in therapeutic baths against monogeneans of C. macropomum.

Refining genomewide association for growth and fat deposition traits in an F pig population.

The identification of genomic regions that affect additive genetic variation and contain genes involved in controlling growth and fat deposition has enormous impact in the farm animal industry (e.g., carcass merit and meat quality). Therefore, a genomewide association study was implemented in an F pig population using a 60,000 SNP marker panel for traits related to growth and fat deposition. Estimated genomic EBV were linearly transformed to calculate SNP effects and to identify genomic positions possibly associated with the genetic variability of each trait. Genomic segments were then defined considering the markers included in a region 1 Mb up- and downstream from the SNP with the smallest -value and a false discovery rate < 0.05 for each trait. The significance for each 2-Mb segment was tested using the Bonferroni correction. Significant SNP were detected on SSC2, SSC3, SSC5, and SSC6, but 2-Mb segment significant effects were observed on SSC3 for weight at birth (wt_birth) and on SSC6 for 10th-rib backfat and last-rib backfat measured by ultrasound at different ages. Furthermore, a 6-Mb segment on SSC6 was also considered because the 2-Mb segments for 10 different fat deposition traits were overlapped. Although the segment effects for each trait remain significant, the proportion of additive variance explained by this larger segment was slightly smaller in some traits. In general, the results confirm the presence of genetic variability for wt_birth on SSC3 (18.0-20.2 Mb) and for fat deposition traits on SSC6 (133.8-136.0 Mb). Within these regions, fibrosin () and myosin light chain, phosphorylatable, fast skeletal muscle () genes could be considered as candidates for the wt_birth signal on SSC3, and the SERPINE1 mRNAbinding protein 1 gene () may be a candidate for the fat deposition trait signals on SSC6.

Meta-analysis of genome-wide association from genomic prediction models.

Genome-wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta-analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal-centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population-level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits.

Implementing meta-analysis from genome-wide association studies for pork quality traits.

Pork quality plays an important role in the meat processing industry. Thus, different methodologies have been implemented to elucidate the genetic architecture of traits affecting meat quality. One of the most common and widely used approaches is to perform genome-wide association (GWA) studies. However, a limitation of many GWA in animal breeding is the limited power due to small sample sizes in animal populations. One alternative is to implement a meta-analysis of GWA (MA-GWA) combining results from independent association studies. The objective of this study was to identify significant genomic regions associated with meat quality traits by performing MA-GWA for 8 different traits in 3 independent pig populations. Results from MA-GWA were used to search for genes possibly associated with the set of evaluated traits. Data from 3 pig data sets (U.S. Meat Animal Research Center, commercial, and Michigan State University Pig Resource Population) were used. A MA was implemented by combining -scores derived for each SNP in every population and then weighting them using the inverse of estimated variance of SNP effects. A search for annotated genes retrieved genes previously reported as candidates for shear force (calpain-1 catalytic subunit [] and calpastatin []), as well as for ultimate pH, purge loss, and cook loss (protein kinase, AMP-activated, γ 3 noncatalytic subunit []). In addition, novel candidate genes were identified for intramuscular fat and cook loss (acyl-CoA synthetase family member 3 mitochondrial []) and for the objective measure of muscle redness, CIE a* (glycogen synthase 1, muscle [] and ferritin, light polypeptide []). Thus, implementation of MA-GWA allowed integration of results for economically relevant traits and identified novel genes to be tested as candidates for meat quality traits in pig populations.

Effects of temperature on transition energies of GaAsSbN/GaAs single quantum wells.

The energy transitions of GaAsSbN/GaAs strained-layer single quantum wells (QWs), grown by molecular-beam epitaxy, are studied in detail, using photoluminescence (PL) and photoreflectance (PR) spectroscopies. The optical transitions energy observed in the PL and PR spectra of GaAsSbN/GaAs QWs show a strong decrease with a small increase in the N composition. These effects are explained through the interaction between the conduction band and a narrow resonant band formed by nitrogen states in the GaAsSbN alloy. The temperature dependence of ground-state energy of strained-layer QWs is analyzed using the Bose-Einstein relation in the temperature range from 9 to 295 K. The parameters that describe the temperature variations of the ground-state energies are evaluated and discussed.

Effects of confinement on the electron-phonon interaction in Al(0.18)Ga(0.82)As/GaAs quantum wells.

Photoluminescence measurements at different temperatures have been performed to investigate the effects of confinement on the electron-phonon interaction in GaAs/AlGaAs quantum wells (QWs). A series of samples with different well widths in the range from 150 up to 750 Å was analyzed. Using a fitting procedure based on the Pässler-p model to describe the temperature dependence of the exciton recombination energy, we determined a fit parameter which is related to the strength of the electron-phonon interaction. On the basis of the behavior of this fit parameter as a function of the well width thickness of the samples investigated, we verified that effects of confinement on the exciton recombination energy are still present in QWs with well widths as large as 450 Å. Our findings also show that the electron-phonon interaction is three times stronger in GaAs bulk material than in Al(0.18)Ga(0.82)As/GaAs QWs.

Identification of the optically active vibrational modes in the photoluminescence of MEH-PPV films.

The temperature dependence of the photoluminescence properties of a thin film of poly[2-methoxy-5-(2(')-ethylhexyloxy)-p-phenylene-vinylene], MEH-PPV, fabricated by spin coating, is analyzed. The evolution with temperature of the peak energy of the purely electronic transition, of the first vibronic band, of the effective conjugation length, and of the Huang-Rhys factors are discussed. The asymmetric character of the pure electronic transition peak and the contribution of the individual vibrational modes to the first vibronic band line shape are considered by a model developed by Cury et al. [J. Chem. Phys. 121, 3836 (2004)]. The temperature dependence of the Huang-Rhys factors of the main vibrational modes pertaining to the first vibronic band allows us to identify two competing vibrational modes. These results show that the electron coupling to different vibrational modes depends on temperature via reduction of thermal disorder.

Occurrence of Sarcopromusca pruna (Diptera) in Southern Brazil as a vector of Dermatobia hominis (Diptera) eggs

Relata-se a ocorrência de Sarcopromusca pruna como vetor biológico de Dermatobia hominis no sul do Brasil. O díptero foi capturado em Janeiro de 2003 em armadilha Malaise, permanentemente instalada desde Julho de 2002, como parte de um estudo de diversidade de Muscoidea no bioma Campos Sulinos, extremo sul do Rio Grande do Sul. O espécime estava carreando 18 ovos de D. hominis na porção látero-ventral direita do abdome

Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study.

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.

[Newborn intestinal colonization by multidrug resistant enterobacteria in a neonatal unit] / Colonização intestinal de recém-natos por enterobactérias multirresistentes a antimicrobianos em unidade neonatal.

OBJECTIVE: To evaluate the occurrence of intestinal colonization in newborns by multidrug-resistant enterobacteria strains (MDRES) during hospital stay after birth. We used selective media in an attempt to determine the relationship between isolation of these strains and some of the presumed colonization risk factors. METHOD: A sequencial inclusion study of 30 newborns was carried out in the neonatal unit of the HUPE, State University Hospital, a general 600-bed tertiary care hospital. We obtained clinical and epidemiological information from medical records and collected a fecal sample from each newborn, which was plated in gentamicin (8mg/ml) medium and potassium tellurite (25mg/ml) medium. The isolated strains were biochemically identified and also submitted to tests of antimicrobial susceptibility. Nine MDRES were submitted to an assay for plasmid conjugational transfer. RESULTS: We isolated 56 distinct MDRES from 14 among 30 newborns (46.7%). Klebsiella pneumoniae was the most common bacterial species (38/56 (68%). We found statistical association between individual MDRES isolation and presence of 3 or 4 of the following colonization risk factors considered: antimicrobial use, low weight (<2.500g), more than 6 days of hospitalization and artificial milk feeding (p< 0.02). We could detect plasmid resistance transfer by bacterial conjugation for 8 among 9 MDRES. CONCLUSION: The seletive cultura media were useful to detect the high frequence of newborns colonized by MDRES in association with well established infection risk factors. We emphasize the importance of reinforcing control rules aiming at preventing intestinal colonization viewed as a risk of nosocomial infection.