RESUMEN
Bacterial contamination causes irreparable losses in the performance of alcoholic fermentation. Antibiotics are used to control these microorganisms, but they generate residues and cause microbial resistance. Today the only commercial product used by the mills is hops, but it is very expensive. As an alternative, the objective of this work was to evaluate the feasibility of using extracts from plants grown in the Cerrado for antimicrobial control during an alcoholic fermentation to replace antibiotics. Hydraethanolic extracts of leaves and essential oil of the following species were tested: Schinus terebinthifolius Raddi, Serjania erecta, Serjania marginata, Campomanesia adamantium and Syzygium cumini. Only the extract of Serjania marginata did not show any activity against the bacterium Bacillus sp. Both the essential oils as well as the hydroalcoholic extracts of S. terebinthifolius and C. adamantium and the extract of S. erecta showed antibacterial activity without harming the yeast, with potential to replace the hops.
Asunto(s)
Fermentación , Extractos Vegetales , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Bacillus , Aceites Volátiles/farmacología , Pruebas de Sensibilidad Microbiana , Bacterias/efectos de los fármacosRESUMEN
Phyllodistomum pepirense n. sp. is described from the urinary bladder of Hoplias malabaricus (Bloch, 1794), sampled in the Jacaré-Pepira River in São Paulo state, Brazil. The isolates of the new species were recovered as a monophyletic group in the phylogenetic analysis of the 28S rRNA gene, which showed the new species as the sister taxa of Phyllodistomum virmantasi Pinacho-Pinacho, Sereno-Uribe, Hernández-Orts, García-Varela & Pérez-Ponce de León, 2021, a species sampled from an eleotrid fish in Southeastern Mexico. The new species differs morphologically from P. virmantasi by having a larger body size, slightly lobed testes and ovary, a mostly intercaecal uterus, slightly diverticulated caeca, and vitelline masses irregularly shaped. The new species is also readily distinguished from other species of Phyllodistomum Braun, 1899 reported from freshwater fishes in Brazil - namely, P. rhamdiae Amato & Amato, 1993 and P. spatula Odhner, 1902. The new species is herein described based on morphological characteristics, molecular data from D1-D3 domains of the 28S rRNA gene, host association, and geographical distribution.
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Characiformes , Trematodos , Animales , Femenino , Brasil , Filogenia , Trematodos/genética , Tamaño Corporal , ARN Ribosómico 28S/genéticaRESUMEN
BACKGROUND AND AIM: Evaluating the protective effect in human enamel of a fluorinated varnish after enduring a citric acid erosive challenge. METHODS: An in vitro model was developed considering the intraoral environment, human saliva and acid erosive procedures. The evaluation of the enamel specimens was undertaken through the direct analysis of enamel by means of Raman spectroscopy and Energy Dispersive X Ray Fluorescence (EDXRF). Ten tooth specimens per group were analysed during three stages: 1- before treatment; 2- After varnish (treatment group) or toothpaste (control) application; 3- After citric acid cycle. Additionally, Particle Induced Gamma Ray emission (PIGE) was used to gauge the fluorine uptake by enamel after the application of the varnish (stage 2). Results were presented as mean and standard deviation with ANOVA and Tukey post hoc performed considering a significance level of 0.05. RESULTS: A significant (p < 0.05) higher Ca levels were detected in treatment group at stage 2 (37.4 ± 0.4 w/w%) and 3 (37.1 ± 0.1) when compared to the control group. After varnish application in treatment group, depolarization ratios were significant lower (p < 0.05) and anisotropy were significant higher (p < 0.05), however no differences were detected in FWHM. CONCLUSIONS: The use of a fluorinated dental varnish suggests a protective effect for human enamel against dental erosion demineralization process which was detectable in an in vitro model.
Asunto(s)
Fluoruro de Sodio , Erosión de los Dientes , Humanos , Fluoruro de Sodio/farmacología , Rayos X , Espectrometría Raman , Análisis de Varianza , Fluoruros/farmacologíaRESUMEN
A new species of Creptotrematina Yamaguti, 1954 was collected from characid fishes, Astyanax fasciatus (Cuvier, 1819) and Astyanax lacustris Lucerna & Soares, 2016 from the Batalha River in the State of Sao Paulo, Brazil. The new species most closely resembles Creptotrematina aguirrepequenoi, but differs by the elongated shape of vitelline follicles, the extension of these follicles in the posterior end of body and the fact that they are not confluent. The morphological differences were confirmed through molecular data. Three specimens were sequenced, and molecular analyses were based on the internal transcribed spacers 2 and D1-D3 domains of the 28S ribosomal RNA gene. The obtained topologies showed the new species as a sister taxon of C. aguirrepequenoi, a species originally described from Astyanax mexicanus in Mexico, and later found in Astyanax aeneus in Costa Rica. Isolates of the new species are reciprocally monophyletic, and genetic distance values are similar to those observed in other species pairs within Allocreadiidae. These findings corroborate that the genus Creptotrematina is mostly a parasite of characids, and widely extended across the Americas, with representative species occurring between Argentina and northern Mexico.
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Characidae/parasitología , Enfermedades de los Peces/parasitología , Trematodos/anatomía & histología , Trematodos/clasificación , Infecciones por Trematodos/veterinaria , Animales , Brasil , ADN de Helmintos/aislamiento & purificación , Femenino , Filogenia , ARN Ribosómico 28S/genética , Ríos , Trematodos/aislamiento & purificación , Infecciones por Trematodos/parasitologíaRESUMEN
Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.
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Lubina/metabolismo , Dieta/veterinaria , Lipogénesis/efectos de los fármacos , Almidón/farmacología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Proteínas en la Dieta/farmacología , Hígado/metabolismoRESUMEN
KEY MESSAGE: Weighted outperformed unweighted genomic prediction using an unbalanced dataset representative of a commercial breeding program. Moreover, the use of the two cycles preceding predictions as training set achieved optimal prediction ability. Predicting the performance of untested single-cross hybrids through genomic prediction (GP) is highly desirable to increase genetic gain. Here, we evaluate the predictive ability (PA) of novel genomic strategies to predict single-cross maize hybrids using an unbalanced historical dataset of a tropical breeding program. Field data comprised 949 single-cross hybrids evaluated from 2006 to 2013, representing eight breeding cycles. Hybrid genotypes were inferred based on their parents' genotypes (inbred lines) using single-nucleotide polymorphism markers obtained via genotyping-by-sequencing. GP analyses were fitted using genomic best linear unbiased prediction via a stage-wise approach, considering two distinct cross-validation schemes. Results highlight the importance of taking into account the uncertainty regarding the adjusted means at each step of a stage-wise analysis, due to the highly unbalanced data structure and the expected heterogeneity of variances across years and locations of a commercial breeding program. Further, an increase in the size of the training set was not always advantageous even in the same breeding program. The use of the two cycles preceding predictions achieved optimal PA of untested single-cross hybrids in a forward prediction scenario, which could be used to replace the first step of field screening. Finally, in addition to the practical and theoretical results applied to maize hybrid breeding programs, the stage-wise analysis performed in this study may be applied to any crop historical unbalanced data.
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Genómica/métodos , Fitomejoramiento/historia , Zea mays/genética , Brasil , Genoma de Planta , Genotipo , Historia del Siglo XXI , Hibridación Genética , Modelos Genéticos , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The present study attempted to provide information regarding non-muscle myosin II (MII) isoforms immunoreactivity in patients with head and neck squamous cell carcinoma (HNSCC) and analysis of the patients' clinical status after 5 years of monitoring. MATERIAL AND METHODS: A semiquantitative analysis of the immunoreactivity of the MII isoforms was performed in 54 surgical specimens and its correlation with clinical and pathological variables and prognosis was verified. Data were analyzed using chi-square, Mann-Whitney and Kruskal-Wallis tests. To evaluate the survival over the total monitoring time and any connection with the proteins studied, the Kaplan-Meier analysis was used. P values ≤0.05 were considered statistically significant. RESULTS: In the advanced stages of pathological tumor-node-metastasis, the expression of MIIB in adjacent non-neoplastic epithelial tissues tended to increase (p = 0.057). In tumoral zones there was an association of high expression among the three isoforms (MIIA/MIIB p=0,001, MIIB/MIIC p=0,006 and MIIA/MIIC p=0,012). Negative clinical evolution in patients was directly correlated to increased MIIC expression in the tumoral zone of invasion in HNSCC (p = 0.017). Based on clinical evolution after the monitoring period, patients with tumors expressing MIIC had poorer prognoses (p = 0.048). CONCLUSIONS: The present study suggests that MIIB expression in non-neoplastic adjacent epithelial tissues may indicate a potential for regional metastasis and that MIIC expression in the tumoral zone of invasion is predictive of negative evolution of the disease.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Biomarcadores de Tumor , Humanos , Miosina Tipo II , PronósticoRESUMEN
Natural products with diverse bioactivities and structures are an important source of novel chemicals with pharmaceutical potentials. Combinations of bioactive compounds with classical antimicrobial agents against drug-resistant or low-susceptible Candida spp. have been studied. Guttiferone-A and its derivatives were combined with fluconazole through the checkerboard method and tested against Candida spp. The results obtained, especially the Fractional Inhibitory Concentration Index (FICI) determined to the combinations, suggests promising results on the treatment of Candida infections, principally for species that present resistance or low antifungal susceptibility. The best result was seen for C. krusei, in which a synergic action of the association between fluconazole and Guttiferone-A resulted in a reduction of more than 100-fold in the alone inhibitory concentration (MIC) of fluconazole. Synergism was also noted in the association of fluconazole with the synthetic derivatives LFQM-79, LFQM-80 and LFQM-81 against C. glabrata, with reduction of up to four times in the alone IC of fluconazole. These results suggest the possibility of combined administration with reduction of doses and side effects of drugs conventionally used against Candida spp. and the promising therapeutic action of Guttiferone-A.
Asunto(s)
Antifúngicos/farmacología , Benzofenonas/farmacología , Candida/efectos de los fármacos , Fluconazol/farmacología , Benzofenonas/química , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Especificidad de la EspecieRESUMEN
BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.
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Antagonistas Adrenérgicos beta/uso terapéutico , Prueba de Esfuerzo/métodos , Hepatopatías/tratamiento farmacológico , Consumo de Oxígeno , Dióxido de Carbono , Estudios Transversales , Várices Esofágicas y Gástricas/tratamiento farmacológico , Femenino , Hemorragia Gastrointestinal/tratamiento farmacológico , Frecuencia Cardíaca , Humanos , Hepatopatías/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
Popcorn is widely consumed in Brazil, yet there are few breeding programs for this crop. Recurrent selection (RS) is a viable breeding alternative for popcorn; however, the gains achieved must be frequently checked. The aim of this study was to assess the effect of selection for grain type (round and pointed) after four cycles of phenotypic RS on the main agronomic traits of popcorn, to estimate the genetic gain achieved for the trait of expansion volume (EV), and to obtain estimates of phenotypic correlations for the main traits of the crop in the UFLA E and UFLA R populations. The zero, one, two, and three cycles of the UFLA E and UFLA R populations, the fourth cycle, and the controls IAC-112 and IAC-125 were used. The experiments were conducted at the experimental farm of Universidade Federal de Lavras (UFLA; Environment 1) and at the experimental area of the Genetics and Plant Breeding Sector of the Department of Biology at UFLA (Environment 2) in the 2010/11 crop season. Nine agronomic traits were evaluated, including EV and grain yield (GY). The UFLA R and UFLA E populations showed similar behavior for all evaluated traits. The type of grain did not affect the genetic gain for EV, which was 5 and 3.7% in each cycle carried out in the UFLA E and UFLA R population, respectively. Phenotypic selection carried out during recombination for EV is an effective method for increasing expression of the trait. EV and GY did not show a linear association.
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Callosidades/genética , Grano Comestible/genética , Carácter Cuantitativo Heredable , Selección Genética , Brasil , Cruzamiento , Cruzamientos Genéticos , Ambiente , FenotipoRESUMEN
BACKGROUND: Over 10,000 US children are diagnosed with cancer yearly. Though outcomes have improved by optimizing conventional therapies, recent immunotherapeutic successes in adult cancers are emerging. Cytotoxic T lymphocytes (CTLs) are the primary executioners of adaptive antitumor immunity and require antigenic presentation in the context of major histocompatibility complex (MHC) class I and the associated ß-2-microglobulin (B2M). Loss of MHC I expression is a common immune escape mechanism in adult malignancies, but pediatric cancers have not been thoroughly characterized. The essential nature of MHC I expression in CTL-mediated cell death may dictate the success of immunotherapies, which rely on eliciting an adaptive response. PROCEDURE: We queried pediatric tumor microarray databases for MHC I and B2M gene expression. We detected MHC I in pediatric tumor cell lines by flow cytometry and characterized MHC I and B2M expression in patient samples by immunohistochemistry. To determine whether therapeutic approaches might enhance MHC I expression in selected models in vitro, we tested effects of exposure to IFN-γ and histone deacetylase inhibitors. RESULTS: Pediatric tumors overall, as well as samples within select individual tumor subtypes, exhibit wide ranges of MHC I and B2M gene and protein expression. For most cell lines tested, MHC I was inducible in vitro. CONCLUSIONS: MHC I and B2M expression vary among pediatric tumor types and should be evaluated as potential biomarkers, which might identify patients most likely to benefit from MHC I dependent immunotherapies. Modulation of MHC I expression may be a promising mechanism for enhancing MHC I dependent immunotherapeutic efficacy.
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Ensayos Clínicos como Asunto/métodos , Antígenos de Histocompatibilidad Clase I/biosíntesis , Inmunoterapia/métodos , Neoplasias/inmunología , Selección de Paciente , Microglobulina beta-2/biosíntesis , Línea Celular Tumoral , Niño , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/análisis , Humanos , Inmunohistoquímica , Neoplasias/terapia , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Matrices Tisulares , Microglobulina beta-2/análisisRESUMEN
The objective of this study was to evaluate the performance of 119 full sib progenies of the fifth cycle of reciprocal recurrent selection (RRS) derived from of Universidade Federal de Lavras maize breeding program. The experiment was carried out in an 11 x 11 triple lattice design at two locations (Lavras, Lambari). The plots consisted of two rows of 3 m, with four plants per 1 m and 0.60 meters of spacing between lines. The grain yield was obtained as kg/plot through weighing of husked ears. The contrast between progenies and controls was not significant, indicating there were no significant differences among the average grain yields of the progenies and controls. When considering the joint analysis, heritability was 64.2%; however, this estimate did not differ from the values estimated for each location separately. Estimates of genetic and phenotypic variance among progenies ranged from 0.21 to 0.28 and 0.30 to 0.47, respectively. Estimates of selection gain, for 10% selection intensity, indicated gains of 16% in the joint analysis of the two locations. The progenies of the fifth cycle of RRS had high average grain yield, associated with high variability. In comparison to the average grain yields exhibited by the controls, it was concluded that the progenies have the potential to be commercially exploited.
Asunto(s)
Cruzamiento , Sitios de Carácter Cuantitativo/genética , Selección Genética/genética , Zea mays/genética , Productos Agrícolas , Cruzamientos Genéticos , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Variación Genética , Zea mays/crecimiento & desarrolloRESUMEN
In this study, we examined the genetic control of the number of leaves above the first ear in maize. The F2 generations and the backcrosses were obtained from 2 contrasting lines for this trait. All generations were assessed in a completely randomized block design with 2 replications. The number of leaves above the ear was counted when the plants were in the tasseling stage at the level of plants per plot. Mean and variance components were estimated using the weighted least square method. We observed a predominance of non-additive effects in the genetic control of number of leaves above the ear. These results indicate that this trait shows high heritability.
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Hojas de la Planta/fisiología , Zea mays/genética , Zea mays/fisiología , Cruzamientos Genéticos , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Variación Genética , Análisis de los Mínimos Cuadrados , Modelos Genéticos , FenotipoRESUMEN
Candida albicans and, more recently, non-C. albicans Candida spp. are considered the most frequent fungi in hospitals. This study analyzed Candida spp. isolates and compared the frequency of different species, that is, C. albicans and non-C. albicans Candida spp., and the origins of isolates, that is, from hospital environments or infections. Yeast virulence factors were evaluated based on biofilm production and metabolic activity. Hemolysin production and the antifungal susceptibility profiles of isolates were also evaluated. Candida spp. were highly prevalent in samples collected from hospital environments, which may provide a reservoir for continuous infections with these yeasts. There were no differences in the biofilm productivity levels and metabolic activities of the environmental and clinical isolates, although the metabolic activities of non-C. albicans Candida spp. biofilms were greater than those of the C. albicans biofilms (p < 0.05). Clinical samples had higher hemolysin production (p < 0.05) and lower susceptibility to fluconazole (p < 0.05). Non-C. albicans Candida spp. predominated in samples collected from hospital environments and infections (p < 0.05). These species had a lower susceptibility to fluconazole and amphotericin B, and their biofilms had higher metabolic activities than those produced by C. albicans, which may explain the increased incidence of fungal infections with these yeasts during recent years.
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Candida/aislamiento & purificación , Candida/fisiología , Candidiasis/microbiología , Microbiología Ambiental , Anfotericina B/farmacología , Antifúngicos/farmacología , Biopelículas/crecimiento & desarrollo , Candida/metabolismo , Candida/patogenicidad , Fluconazol/farmacología , Proteínas Hemolisinas/metabolismo , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , PrevalenciaRESUMEN
The aim of this article is to investigate patient satisfaction, survival rate of implants, and prosthetic complications or maintenance for rehabilitation with removable partial dentures associated with implants in mandibular Kennedy class I and II cases. A systematic literature review was conducted by three independent reviewers including articles published from January 1981 through September 2011. Medline and Cochrane Library electronic databases were used in addition to hand searching to assess clinical outcomes for mandibular implant-supported removable partial denture with distal extension. This review yielded 1751 records that were narrowed down to 5. The studies revealed implant survival rates ranging from 95% to 100% with one failure reported of 98 implants. The removable partial dentures associated with implant in mandibular free-end arches showed some complications and need of repair for relining, pitting of the healing abutment, replacement of resilient component of the attachment, damage in framework, screw loosening and damage in acrylic denture base. Patient satisfaction was evaluated through a five-point questionnaire, and results ranged between 4.12 and 5.0, considering 1 as the least favourable situation. The literature review showed increase in patient satisfaction and high survival rates of implants associated with mandibular removable partial dentures with distal extensions. However, some complications and need of prosthetic repair were reported. Although this treatment approach could represent a low-cost and beneficial rehabilitation for free-end mandibular ridges, the lack of controlled and randomised well-designed clinical trials suggests further studies with more representative samples to validate the outcomes of this treatment modality.
Asunto(s)
Prótesis Dental de Soporte Implantado/normas , Dentadura Parcial Removible/normas , Arcada Parcialmente Edéntula/rehabilitación , Satisfacción del Paciente , Pilares Dentales , Implantes Dentales , Prótesis Dental de Soporte Implantado/efectos adversos , Retención de Dentadura , Dentadura Parcial Removible/efectos adversos , Humanos , Arcada Parcialmente Edéntula/cirugía , Mandíbula/cirugía , Masticación/fisiología , Falla de Prótesis , Calidad de Vida , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the effects of different pretreatments on the bond strength of a dual-cure resin core to 3 types of fiber posts. Bond strength was measured using a push-out design. One-sided t-Test of Hypothesis with unknown variance was performed (p-values < 5%). Sandblasting abrasion with 50 micro alumina particles at a specific distance, pressure and time was the only surface treatment in DT Light Post and Transluma Post that increased the bond strength to dual cure resin composite cores. FRC Postec Plus post did not shown an increase in bond strength in any group.
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Resinas Compuestas/química , Recubrimiento Dental Adhesivo/métodos , Grabado Dental/métodos , Análisis del Estrés Dental , Técnica de Perno Muñón , Vidrio , Ensayo de Materiales , Cuarzo , Cementos de Resina , Auto-Curación de Resinas Dentales , Propiedades de SuperficieRESUMEN
The aim of this study was to describe a technique and report the success of a clinical case in which a modified technique of in-office bleaching with hydrogen peroxide at 35% was performed for two sessions in a premolar pigmented by amalgam followed by placement of a posterior direct composite resin restoration.
Asunto(s)
Amalgama Dental/efectos adversos , Blanqueamiento de Dientes/métodos , Decoloración de Dientes/etiología , Decoloración de Dientes/terapia , Adulto , Diente Premolar , Corrosión , Femenino , Humanos , Peróxido de Hidrógeno/administración & dosificación , Retratamiento , Blanqueadores Dentales/administración & dosificaciónRESUMEN
Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.
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Anomalías Múltiples/genética , Antígenos de Neoplasias/genética , Cilios , Proteínas de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Secuencia de Bases , Proteínas de Ciclo Celular , Cilios/genética , Cilios/patología , Proteínas del Citoesqueleto , Análisis Mutacional de ADN , Femenino , Feto/metabolismo , Feto/patología , Eliminación de Gen , Pruebas Genéticas , Humanos , Proteínas de Neoplasias/metabolismo , ARN Mensajero/análisis , SíndromeRESUMEN
The aim of this study was to investigate the pharmacological effects of discretamine, an isoquinoline alkaloid isolated from Duguetia magnolioidea Maas, on the cardiovascular system, using a combined in vivo and in vitro approach. Blood pressure and heart rate measurements, as well as changes in isometric tension in rat superior mesenteric arterial rings, elicited by discretamine were recorded. In normotensive non-anaesthetized rats (n = 6), discretamine (0.01; 0.05; 0.1; 0.5; 1, 5 and 10 mg/kg i.v., randomly) injections produced hypotension (-5.2 +/- 1.7; -5.1 +/- 2.1; -7.7 +/- 2; -8.9 +/- 1.7; -9.6 +/- 2.2; -16.8 +/- 2.8 and -13.4 +/- 1.3 mmHg, respectively) accompanied by tachycardia (24.2 +/- 6.1; 36.8 +/- 11.3; 44.2 +/- 7.7; 45.9 +/- 6.4; 48.2 +/- 9.1; 72.1 +/- 14.5 and 64 +/- 17 bpm, respectively). Hypotensive and tachycardic responses were significantly attenuated after L-NAME (20 mg/kg, i.v.) administration. In isolated rat mesenteric artery rings, with endothelium intact, discretamine (10(-12) - 10(-5) M) induced concentration-dependent relaxation of the contractions induced by phenylephrine (10 microM) [pD2 = 6.8 +/- 0.1]. The effect of the discretamine on phenylephrine induced contractions was significantly attenuated after removal of the vascular endothelium [pD2 = 5.8 +/- 0.04]. Similar results were obtained after pre-treatment with L-NAME 100 microM [pD2 = 5.8 +/- 0.04], L-NAME 300 microM [pD2 = 5.9 +/- 0.06], Hydroxocobalamin 30 microM [pD2 = 5.8 +/- 0.06] or ODQ 10 microM [pD2 = 5.8 +/- 0.04]. In addition, in rabbit aorta endothelial cell line, discretamine significantly increased NO3- levels. These results suggest that the hypotensive effect induced by discretamine is probably due to a peripheral vasodilatation, at least, in part, due to the release of NO from vascular endothelium and consequent activation of soluble guanylyl cyclase (GC) in the vascular smooth muscle cells.
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Antihipertensivos/farmacología , Alcaloides de Berberina/farmacología , Endotelio Vascular/fisiología , Factores Relajantes Endotelio-Dependientes/fisiología , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Arterias Mesentéricas/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Óxido Nítrico/metabolismo , Conejos , Ratas , Ratas WistarRESUMEN
BACKGROUND: Hand stereotypies are considered a hallmark of Rett syndrome (RTT) and are usually described as symmetric movements at the midline. However, related pathologies may show the same type of involuntary movement. Furthermore, patients with RTT also have stereotypies with other localizations that are less well characterized. METHODS: We analyzed stereotypies in 83 patients with RTT, 53 with and 30 without a mutation detected in the MECP2 gene. Patients were observed and videotaped always by the same pediatric neurologist. Stereotypies were classified, and data were submitted to statistical analysis for comparison of mutation-positive and -negative patients and analysis of their evolution with the disease. RESULTS: All the patients showed hand stereotypies that coincided with or preceded the loss of purposeful hand movements in 62% of the patients with MECP2 mutations. The hair pulling stereotypy was more frequent in the group with detected mutations, whereas hand washing was not. Hand gaze was absent in all RTT patients with MECP2 mutations. Patients with MECP2 mutations also had more varied stereotypies, and the number of stereotypies displayed by each patient decreased significantly with age in this group. In all patients, stereotypies other than manual tended to disappear with the evolution of the disease. CONCLUSIONS: Although symmetric midline hand stereotypies were not specific to patients with an MECP2 mutation, some of the other stereotypies seemed to be more characteristic of this group. In patients younger than 10 years and meeting the necessary diagnostic criteria of Rett syndrome, the association of hand stereotypies without hand gaze, bruxism, and two or more of the other stereotypies seemed to be highly indicative of the presence of an MECP2 mutation.