[Comparison of tiapride and topiramate in the prophylactic treatment of chronic migraine: a randomised, double-blind, pilot study]. / Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego.

AIM: The aim of this study was to evaluate the efficacy and safety of tiapride compared to topiramate as a prophylactic in chronic migraine. PATIENTS AND METHODS: The study was conducted under randomised and double blind conditions. A total of 56 patients aged 18-65 years with chronic migraine were assigned to two treatment arms: tiapride, 100 mg twice daily, or topiramate, 25 mg twice daily, for 12 weeks. The primary endpoint was the change in the monthly average number of migraine days. In addition, measurements were performed to determine the change in the monthly number of headache days, the percentage of subjects with >50% and >75% decrease in their monthly migraine days, and the change in headache impact as measured by the Headache Impact Test-6. RESULTS: The intention-to-treat population included 39 subjects (tiapride = 21; topiramate = 18), 35 of whom (tiapride = 18; topiramate = 16) completed the trial. The tiapride group had a mean reduction of 7.2 ± 7.5 migraine days per month compared to 7.6 ± 5.8 for the topiramate group (p = 0.86). As with the other efficacy variables measured, no differences were found between the two groups. Adverse side effects were mild in both groups. CONCLUSION: In patients with chronic migraine, tiapride was found to be an effective, safe and well-tolerated prophylactic treatment when compared to topiramate.

TITLE: Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego.Objetivo. Evaluar la eficacia y la seguridad de la tiaprida en comparación con el topiramato en la profilaxis de la migraña crónica. Pacientes y métodos. Es un estudio aleatorizado y doble ciego. Un total de 56 pacientes de 18 a 65 años con migraña crónica fueron asignados a dos brazos de tratamiento: tiaprida, 100 mg dos veces al día, o topiramato, 25 mg dos veces al día, durante 12 semanas. El criterio de valoración principal fue el cambio en el promedio mensual de días de migraña. Además, se midió el cambio en el número mensual de días de cefalea, el porcentaje de sujetos con disminución > 50% y > 75% de sus días de migraña mensual, y el cambio del impacto de la cefalea medido por el Headache Impact Test-6. Resultados. La población por intención de tratar incluyó a 39 sujetos (tiaprida = 21; topiramato = 18) y completaron el ensayo 35 participantes (tiaprida = 18; topiramato = 16). El grupo con tiaprida tuvo una reducción media de 7,2 ± 7,5 días con migrañas por mes en comparación con 7,6 ± 5,8 para el grupo con topiramato (p = 0,86). Al igual que en las otras variables de eficacia medidas, no hubo diferencias significativas entre ambos grupos. Los efectos adversos fueron leves en ambos grupos. Conclusión. En pacientes con migraña crónica, la tiaprida demostró ser un tratamiento profiláctico eficaz, seguro y bien tolerado, al compararla con el topiramato.

Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego / Comparison of tiapride and topiramate in the prophylactic treatment of chronic migraine: a randomised, double-blind, pilot study

Objetivo: Evaluar la eficacia y la seguridad de la tiaprida en comparación con el topiramato en la profilaxis de la migraña crónica. Pacientes y métodos: Es un estudio aleatorizado y doble ciego. Un total de 56 pacientes de 18 a 65 años con migraña crónica fueron asignados a dos brazos de tratamiento: tiaprida, 100 mg dos veces al día, o topiramato, 25 mg dos veces al día, durante 12 semanas. El criterio de valoración principal fue el cambio en el promedio mensual de días de migraña. Además, se midió el cambio en el número mensual de días de cefalea, el porcentaje de sujetos con disminución > 50% y > 75% de sus días de migraña mensual, y el cambio del impacto de la cefalea medido por el Headache Impact Test-6. Resultados: La población por intención de tratar incluyó a 39 sujetos (tiaprida = 21; topiramato = 18) y completaron el ensayo 35 participantes (tiaprida = 18; topiramato = 16). El grupo con tiaprida tuvo una reducción media de 7,2 ± 7,5 días con migrañas por mes en comparación con 7,6 ± 5,8 para el grupo con topiramato (p = 0,86). Al igual que en las otras variables de eficacia medidas, no hubo diferencias significativas entre ambos grupos. Los efectos adversos fueron leves en ambos grupos. Conclusión: En pacientes con migraña crónica, la tiaprida demostró ser un tratamiento profiláctico eficaz, seguro y bien tolerado, al compararla con el topiramato.(AU)

Aim: The aim of this study was to evaluate the efficacy and safety of tiapride compared to topiramate as a prophylactic in chronic migraine. Patients and methods: The study was conducted under randomised and double blind conditions. A total of 56 patients aged 18-65 years with chronic migraine were assigned to two treatment arms: tiapride, 100 mg twice daily, or topiramate, 25 mg twice daily, for 12 weeks. The primary endpoint was the change in the monthly average number of migraine days. In addition, measurements were performed to determine the change in the monthly number of headache days, the percentage of subjects with >50% and >75% decrease in their monthly migraine days, and the change in headache impact as measured by the Headache Impact Test-6. Results: The intention-to-treat population included 39 subjects (tiapride = 21; topiramate = 18), 35 of whom (tiapride = 18; topiramate = 16) completed the trial. The tiapride group had a mean reduction of 7.2 ± 7.5 migraine days per month compared to 7.6 ± 5.8 for the topiramate group (p = 0.86). As with the other efficacy variables measured, no differences were found between the two groups. Adverse side effects were mild in both groups. Conclusion. In patients with chronic migraine, tiapride was found to be an effective, safe and well-tolerated prophylactic treatment when compared to topiramate.(AU)

Spread of the fascioliasis endemic area assessed by seasonal follow-up of rDNA ITS-2 sequenced lymnaeid populations in Cajamarca, Peru.

Fascioliasis is a worldwide emerging snail-borne zoonotic trematodiasis with a great spreading capacity linked to animal and human movements, climate change, and anthropogenic modifications of freshwater environments. South America is the continent with more human endemic areas caused by Fasciola hepatica, mainly in high altitude areas of Andean regions. The Peruvian Cajamarca area presents the highest human prevalences reported, only lower than those in the Bolivian Altiplano. Sequencing of the complete rDNA ITS-2 allowed for the specific and haplotype classification of lymnaeid snails collected in seasonal field surveys along a transect including 2007-3473 m altitudes. The species Galba truncatula (one haplotype preferentially in higher altitudes) and Pseudosuccinea columella (one haplotype in an isolated population), and the non-transmitting species Lymnaea schirazensis (two haplotypes mainly in lower altitudes) were found. Climatic seasonality proved to influence G. truncatula populations in temporarily dried habitats, whereas L. schirazensis appeared to be more climatologically independent due to its extreme amphibious ecology. Along the southeastern transect from Cajamarca city, G. truncatula and L. schirazensis shared the same site in 7 localities (46.7% of the water collections studied). The detection of G. truncatula in 11 new foci (73.3%), predominantly in northern localities closer to the city, demonstrate that the Cajamarca transmission risk area is markedly wider than previously considered. Lymnaea schirazensis progressively increases its presence when moving away from the city. Results highlight the usefulness of lymnaeid surveys to assess borders of the endemic area and inner distribution of transmission foci. Similar lymnaeid surveys are still in need to be performed in the wide northern and western zones of the Cajamarca city. The coexistence of more than one lymnaeid transmitting species, together with a morphologically indistinguishable non-transmitting species and livestock movements inside the area, conform a complex scenario which poses difficulties for the needed One Health control intervention.

Recurrencia del síndrome de área motora suplementaria en meningiomas parasagitales recidivados: del evento al origen / Recurrent supplementary motor area syndrome in relapsed parasagittal meningiomas: from the onset to the origin

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Development of liquid chromatography tandem mass spectrometry method to quantify cyclobutane pyrimidine dimer photolyase activity by detection of 15mer oligonucleotide as reaction product.

Ultraviolet radiation from sunlight causes DNA damage in skin cells by formation of photoproducts, mainly cyclobutane pyrimidine dimers (CPD), which are reverted by exogenous CPD-photolyase, preventing photoaging and skin cancer. High performance liquid chromatography tandem mass spectrometry method for quantification of CPD-photolyase activity was developed to search new enzymes sources for dermatology or clinical studies. The method was based in the enzymatic conversion of a 15mer oligonucleotide, containing a center cyclobutane thymidine dimer, to the restored 15mer oligonucleotide. Three ion pair reagent were evaluated by response surface methodology to increase mass intensities. Additionally, chromatographic separation of oligonucleotides was performed. The selected mobile phase was 15 mM diisopropylethylamine/20 mM hexafluoroisopropanol in methanol. The method allowed total separation between the oligonucleotides studied (resolution of 2.3) by using the core shell technology, which reduce the diffusion time of the analyte into the column, increasing the efficiency and minimizing the analysis time at 7 min. The mass spectrometry detection allowed a high selectivity and sensitivity. This is the first time where MRM modality has been employed with this specific purpose. Oligonucleotides recovery from reaction mixture was ∼ 94% and the limit of quantification was 13.4 nM for 15mer. The method was evaluated with a recombinant CPD-photolyase from Synechococcus leopoliensis using purified and crude protein extract. CPD-photolyase could be measured in terms of activity for enzymatic kinetics studies, for evaluation of UV-R effects in (micro)organisms and to identify new enzymes.

Severity of Candida-associated denture stomatitis is improved in institutionalized elders who consume Lactobacillus rhamnosus SP1.

BACKGROUND: This study aimed to determine the effect of the consumption of a probiotic on the clinical characteristics of Candida-associated denture stomatitis (DS) and to determine the impact of a protocol of self-care measures in oral/prosthetic hygiene in institutionalized elders that wear removable prostheses (RP). The current treatment for DS is the systemic use of antifungals, as well as the replacement of these devices together with oral/prosthetic hygiene instructions. METHODS: This study was a randomized, controlled and triple-blind trial. Thirty-six elders presenting DS of different severity and who carried RP consumed milk with/without the probiotic L. rhamnosus SP1. The prevalence and severity of DS and prevalence of Candida were determined and all participants/caregivers were trained in oral/prosthetic hygiene. RESULTS: In both groups a decrease in the prevalence of DS was observed (P < 0.05) but only the group that consumed probiotic throughout the trial had a significant reduction in the severity of DS and reduced Candida counts (P < 0.05). Educational instruction in oral/prosthetic hygiene was relevant for the participants, regarding the prevalence of this lesion. CONCLUSIONS: The frequent consumption of Lactobacillus rhamnosus SP1 and the establishment of a protocol of oral/prosthetic hygiene drastically reduced the severity of DS in institutionalized elders who wore RP.

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r2=0.98-1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml-1 of IL-18 after adjusting for covariates (rs80011693; rs111311302 ß=-0.06, P-value=2.7 × 10-4). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections.

Computational comparison of aortic root stresses in presence of stentless and stented aortic valve bio-prostheses.

We provide a computational comparison of the performance of stentless and stented aortic prostheses, in terms of aortic root displacements and internal stresses. To this aim, we consider three real patients; for each of them, we draw the two prostheses configurations, which are characterized by different mechanical properties and we also consider the native configuration. For each of these scenarios, we solve the fluid-structure interaction problem arising between blood and aortic root, through Finite Elements. In particular, the Arbitrary Lagrangian-Eulerian formulation is used for the numerical solution of the fluid-dynamic equations and a hyperelastic material model is adopted to predict the mechanical response of the aortic wall and the two prostheses. The computational results are analyzed in terms of aortic flow, internal wall stresses and aortic wall/prosthesis displacements; a quantitative comparison of the mechanical behavior of the three scenarios is reported. The numerical results highlight a good agreement between stentless and native displacements and internal wall stresses, whereas higher/non-physiological stresses are found for the stented case.

Improved hybrid/GPU algorithm for solving cardiac electrophysiology problems on Purkinje networks.

Cardiac Purkinje fibers provide an important pathway to the coordinated contraction of the heart. We present a numerical algorithm for the solution of electrophysiology problems across the Purkinje network that is efficient enough to be used in in silico studies on realistic Purkinje networks with physiologically detailed models of ion exchange at the cell membrane. The algorithm is on the basis of operator splitting and is provided with 3 different implementations: pure CPU, hybrid CPU/GPU, and pure GPU. Compared to our previous work, we modify the explicit gap junction term at network bifurcations to improve its mathematical consistency. Due to this improved consistency of the model, we are able to perform an empirical convergence study against analytical solutions. The study verified that all 3 implementations produce equivalent convergence rates, and shows that the algorithm produces equivalent result across different hardware platforms. Finally, we compare the efficiency of all 3 implementations on Purkinje networks of increasing spatial resolution using membrane models of increasing complexity. Both hybrid and pure GPU implementations outperform the pure CPU implementation, but their relative performance difference depends on the size of the Purkinje network and the complexity of the membrane model used.

Correlación del score de gleason en biopsia prostática con el de pieza operatoria. ¿Cuál es nuestro porcentaje de upgrading? / Correlation between Gleason Score of prostate biopsy and prostatectomy specimen. ¿How high is our upgrading rate?

Introducción. El cáncer de próstata es el segundo cáncer más prevalente del mundo y ocupa el quinto lugar en mortalidad en hombres. El score de Gleason es el factor pronósticos más importante. Sin embargo, numerosos estudios han reportado diferencias entre el score de Gleason de la biopsia prostática y el obtenido de la pieza operatoria. Es por este motivo que el objetivo del presente estudio, es evaluar la concordancia entre el score de Gleason de la biopsia prostática transrectal comparado con el de la pieza operatoria de la prostatectomia radical.(AU)

Introduction. Prostate cancer is the second most prevalent cancer in the world, and occupies the fifth place in mortality among men. Gleason score (GS) is the most important prognostic factor. However, a number of studies have reported differences between the GS of the trans rectal biopsy and the prostatectomy specimen. That is the reason of the this study, our objective is to evaluate concordance between Gleason scores, of the biopsy and the prostatectomy specimen.(AU)

Life cycle assessment of carbon capture and utilization from ammonia process in Mexico.

Post-combustion CO2 capture (PCC) of flue gas from an ammonia plant (AP) and the environmental performance of the carbon capture utilization (CCU) technology for greenhouse gas (GHG) emissions to an enhanced oil recovery (EOR) system in Mexico was performed as case study. The process simulations (PS) and life cycle assessment (LCA) were used as supporting tools to quantify the CO2 capture and their environmental impacts, respectively. Two scenarios were considered: 1) the AP with its shift and CO2 removal unit and 2) Scenario 1 plus PCC of the flue gas from the AP primary reformer (AP-2CO2) and the global warming (GW) impact. Also, the GW of the whole of a CO2-EOR project, from these two streams of captured CO2, was evaluated. Results show that 372,426 tCO2/year can be PCC from the flue gas of the primary reformer and 480,000 tons/y of capacity from the AP. The energy requirement for solvent regeneration is estimated to be 2.8 MJ/kgCO2 or a GW impact of 0.22 kgCO2e/kgCO2 captured. GW performances are 297.6 kgCO2e emitted/barrel (bbl) for scenario one, and 106.5 kgCO2e emitted/bbl for the second. The net emissions, in scenario one, were 0.52 tCO2e/bbl and 0.33 tCO2e/bbl in scenario two. Based on PS, this study could be used to evaluate the potential of CO2 capture of 4080 t/d of 4 ammonia plants. The integration of PS-LCA to a PCC study allows the applicability as methodological framework for the development of a cluster of projects in which of CO2 could be recycled back to fuel, chemical, petrochemical products or for enhanced oil recovery (EOR). With AP-2CO2, "CO2 emission free" ammonia production could be achieved.

Association between disease occurrence and fertility of dairy cows in three geographic regions of Chile.

The objective was to analyze the association between disease occurrence during early lactation and reproductive performance and survival of dairy cows in high-producing herds, under different management practices in three geographic regions of Chile. Data included 30,757 lactation records of cows calving from January 2013 to June 2014 in three different locations: Central (C) area (n = 6198 cows in eight herds), Central-South (CS) area(n = 17,234 cows in 12 herds), and South (S) area (n = 7325 cows in six herds). Data were analyzed using logistic regression and ANOVA, considering cow as the experimental unit. Covariables offered to the models included parity number, season of calving, cow and herd relative milk yield, geographic location, and management system. Average milk yield (305 ME) per cow were 12,091, 11,783, and 6852 kg for C, CS, and S regions, respectively. Time from calving to first service and time to conception were consistently greater for cows with at least one disease event within 50 days in milk (DIM), for cows that were reported lame, or for cows that had mastitis or metritis. The odds (95% confidence interval) of pregnancy at 150 DIM (P150) and the odds of survival until 150 DIM (S150) for cows that had at least one disease event within 50 DIM were 0.84 (0.79-0.91) times the odds of pregnancy and 0.25 (0.22-0.28) times the odds of survival for healthy cows. The odds of P150 for cows located in the C and CS areas were 1.56 (1.36-1.80) and 1.16 (1.04-1.30) times the odds of P150 for cows in the S area. The odds of S150 for cows located in the C and CS areas were 0.48 (0.37-0.62) and 0.54 (0.42-0.67) times the odds of S150 for cows in the S area. These data suggested that cow health status and geographic location are significantly associated with reproductive performance and survival in this population of Chilean dairy cows.

Comparison of Ant Community Diversity and Functional Group Composition Associated to Land Use Change in a Seasonally Dry Oak Forest.

Ants have been used to assess land use conversion, because they reflect environmental change, and their response to these changes have been useful in the identification of bioindicators. We evaluated ant diversity and composition associated to different land use change in a temperate forest (above 2000 m asl) in Mexico. The study was carried out in "Flor del Bosque" Park a vegetation mosaic of native Oak Forests and introduced Eucalyptus and grasslands. Species richness, dominance and diversity rarefaction curves, based on ant morphospecies and functional groups, were constructed and compared among the three vegetation types, for the rainy and the dry seasons of 2008-2009. Jaccard and Sorensen incidence-based indices were calculated to obtain similarity values among all the habitats. The Oak Forest was a rich dominant community, both in species and functional groups; the Eucalyptus plantation was diverse with low dominance. The most seasonality habitat was the grassland, with low species and high functional group diversity during the dry seasons, but the reverse pattern during the wet season. The Oak Forest was more similar to the Eucalyptus plantation than to the grassland, particularly during the dry season. Oak Forests are dominated by Cold Climate Specialists, specifically Prenolepis imparis (Say). The Eucalyptus and the grassland are characterized by generalized Myrmicinae, as Pheidole spp. and Monomorium ebenium (Forel). The conservation of the native Oak Forest is primordial for the maintenance of Cold Climate Specialist ant communities. The microclimatic conditions in this forest, probably, prevented the invasion by opportunistic species.

Molecular phylogenetics of the white-lipped peccary (Tayassu pecari) did not confirm morphological subspecies in northwestern South America.

We sequenced the mitochondrial DNA (mtDNA) control region of 59 peccaries (44 white-lipped peccaries, Tayassu pecari, and 15 collared peccaries, Pecari tajacu). We also genotyped 3 DNA microsatellites from 78 white-lipped peccaries representing the 4 putative morphological subspecies (i.e., spiradens, aequatoris, pecari, and albirostris) present in northwestern South America (i.e., Colombia, Ecuador, Peru, and Bolivia). Our results showed: 1) the estimated diversity of the mtDNA control region in the T. pecari population was extremely high, whereas the average genetic diversity for the microsatellites was medium to high and similar to that observed in European pig breeds; 2) there was no significant genetic heterogeneity among the quoted putative morphological subspecies at the mitochondrial marker, but we did detect significant (although relatively small) genetic heterogeneity using microsatellites, indicating that T. pecari albirostris is a uniquely differentiated group; and 3) the phylogenetic mtDNA trees showed that haplotypes were intermixed independent of their "a priori" subspecies classification. In addition, the microsatellite assignation analyses yielded low percentages of well-classified individuals when the analysis considered the geographic morphology of the subspecies. Thus, the molecular results do not support the putative morphological subspecies of T. pecari in northwestern South America. Finally, our results did not detect clear historical demographic changes using the mtDNA control region sequences. These genetic results are discussed in the context of the ecological and social characteristics of T. pecari.

Influence of the aortic valve leaflets on the fluid-dynamics in aorta in presence of a normally functioning bicuspid valve.

In this work, we consider the blood fluid-dynamics in the ascending aorta in presence of a normally functioning bicuspid aortic valve (BAV). In particular, we perform an unsteady finite element study in real geometries with physiological velocity boundary conditions at the inlet to assess the effect of the inclusion of the leaflets on the fluid-dynamic abnormalities characterizing BAV cases. To this aim, we perform a comparison in two geometries (a dilated and a non-dilated ones) among three scenarios which are built up for each geometry: BAV without leaflets, BAV with leaflets, and tricuspid case with leaflets. For each case, we compute four indices quantifying flow asymmetry, reversal flows, helical patterns, and wall shear stresses. Our results show that the inclusion of the leaflets increases the fluid-dynamics abnormalities, especially for the non-dilated configuration, which presents a greater increment of the indices. In particular, we observe that the values of the time-averaged wall shear stress and of the systolic jet asymmetry increase by approximatively 100 and 40%, respectively, when considering the leaflets.

Detection of hepatitis E virus genome in pig livers in Antioquia, Colombia.

Hepatitis E is a form of endemic acute hepatitis found in humans in many countries worldwide and is caused by the hepatitis E Virus (HEV). Detection of HEV in pigs indicates that they may be carriers, possibly through zoonosis. The prevalence of HEV in pigs in Colombia is unknown. Studies in the US found that 11% of pig livers sold in grocery stores are contaminated with HEV. It is also known that HEV can be inactivated when cooked, as it is labile to high temperatures. The aim of this study was to determine HEV contamination in pig livers sold in Medellín, Antioquia. A total of 150 livers from 5 slaughterhouses and 100 livers in grocery stores from different social strata of the city of Medellin analyzed to detect a segment of the HEV open reading frame-1 using reverse transcription-polymerase chain reaction. The results showed that 41.3% of pig livers from slaughterhouses and 25% of livers from grocery stores tested positive for HEV. Thus, the HEV genome is present in pig livers sold in Antioquia, revealing the presence of this virus in pigs from Colombia and the need subject entrails to proper cooking processes before consumption. Further research is required to determine the role of this virus in public health and pork production in Colombia.

Role of PrP(C) Expression in Tau Protein Levels and Phosphorylation in Alzheimer's Disease Evolution.

Alzheimer's disease (AD) is characterized by the presence of amyloid plaques mainly consisting of hydrophobic ß-amyloid peptide (Aß) aggregates and neurofibrillary tangles (NFTs) composed principally of hyperphosphorylated tau. Aß oligomers have been described as the earliest effectors to negatively affect synaptic structure and plasticity in the affected brains, and cellular prion protein (PrP(C)) has been proposed as receptor for these oligomers. The most widely accepted theory holds that the toxic effects of Aß are upstream of change in tau, a neuronal microtubule-associated protein that promotes the polymerization and stabilization of microtubules. However, tau is considered decisive for the progression of neurodegeneration, and, indeed, tau pathology correlates well with clinical symptoms such as dementia. Different pathways can lead to abnormal phosphorylation, and, as a consequence, tau aggregates into paired helical filaments (PHF) and later on into NFTs. Reported data suggest a regulatory tendency of PrP(C) expression in the development of AD, and a putative relationship between PrP(C) and tau processing is emerging. However, the role of tau/PrP(C) interaction in AD is poorly understood. In this study, we show increased susceptibility to Aß-derived diffusible ligands (ADDLs) in neuronal primary cultures from PrP(C) knockout mice, compared to wild-type, which correlates with increased tau expression. Moreover, we found increased PrP(C) expression that paralleled with tau at early ages in an AD murine model and in early Braak stages of AD in affected individuals. Taken together, these results suggest a protective role for PrP(C) in AD by downregulating tau expression, and they point to this protein as being crucial in the molecular events that lead to neurodegeneration in AD.

Expression and enzymatic activity of phenylalanine ammonia-lyase and p-coumarate 3-hydroxylase in mango (Mangifera indica 'Ataulfo') during ripening.

Phenylalanine ammonia lyase (PAL) and p-coumarate 3-hydroxylase (C3H) are key enzymes in the phenylpropanoid pathway. The relative expression of PAL and C3H was evaluated in mango fruit cultivar 'Ataulfo' in four ripening stages (RS1, RS2, RS3, and RS4) by quantitative polymerase chain reaction. In addition, enzyme activity of PAL and C3H was determined in mango fruits during ripening. The PAL levels were downregulated at the RS2 and RS3 stages, while C3H levels were upregulated in fruits only at RS3. The enzyme activity of PAL followed a pattern that was different from that of the PAL expression, thus suggesting regulation at several levels. For C3H, a regulation at the transcriptional level is suggested because a similar pattern was revealed by its activity and transcript level. In this study, the complexity of secondary metabolite biosynthesis regulation is emphasized because PAL and C3H enzymes are involved in the biosynthesis of several secondary metabolites that are active during all mango ripening stages.