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1.
Acta Physiol (Oxf) ; 240(3): e14111, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38314948

RESUMO

AIM: This study aimed to investigate the effects of caffeine on pathways associated with mitochondrial quality control and mitochondrial capacity during skeletal muscle regeneration, focusing on the role of Parkin, a key protein involved in mitophagy. METHODS: We used in vitro C2C12 myoblast during differentiation with and without caffeine in the medium, and we evaluated several markers of mitochondrial quality control pathways and myotube growth. In vivo experiments, we used C57BL/6J (WT) and Parkintm 1Shn lineage (Parkin-/- ) mice and injured tibial anterior muscle. The mice regenerated TA muscle for 3, 10, and 21 days with or without caffeine ingestion. TA muscle was used to analyze the protein content of several markers of mitochondrial quality pathways, muscle satellite cell differentiation, and protein synthesis. Furthermore, it analyzed mtDNA, mitochondrial respiration, and myofiber growth. RESULTS: C2C12 differentiation experiments showed that caffeine decreased Parkin content, potentially leading to increased DRP1 and PGC-1α content and altered mitochondrial population, thereby enhancing growth capacity. Using Parkin-/- mice, we found that caffeine intake during the regenerative process induces an increase in AMPKα phosphorylation and PGC-1α and TFAM content, changes that were partly Parkin-dependent. In addition, the absence of Parkin potentiates the ergogenic effect of caffeine by increasing mitochondrial capacity and myotube growth. Those effects are related to increased ATF4 content and activation of protein synthesis pathways, such as increased 4E-BP1 phosphorylation. CONCLUSION: These findings demonstrate that caffeine ingestion changes mitochondrial quality control during skeletal muscle regeneration, and Parkin is a central player in those mechanisms.


Assuntos
Cafeína , Músculo Esquelético , Camundongos , Animais , Cafeína/farmacologia , Músculo Esquelético/metabolismo , Camundongos Endogâmicos C57BL , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regeneração
2.
J Dent Res ; 103(4): 427-433, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38284313

RESUMO

The phosphate ester monomer 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) is capable of bonding to hydroxyapatite and, for this reason, is a key component of several self-etch adhesives. In this study, dicalcium phosphate dihydrate particles (DCPD; CaHPO4.2H2O) were functionalized with 10-MDP and used to formulate an experimental composite with 50 vol% inorganic content (3:1 DCPD:silanated barium glass ratio) dispersed in a BisGMA/TEGDMA matrix. The tested hypothesis was that DCPD functionalization would improve the composite's mechanical performance without compromising Ca2+ release. Composites containing nonfunctionalized DCPD or only reinforcing glass (in both cases, with or without 10-MDP mixed in the resin phase) were used as controls. Materials were tested for degree of conversion (DC; by Fourier transform infrared spectroscopy), water sorption (WS) and solubility (SL; according to ISO 4049), biaxial flexural strength (BFS)/modulus (FM) after 24 h and 5 mo in water, and 28-d Ca2+ release in water (by plasma-coupled optical emission spectroscopy). Data were analyzed using analysis of variance/Tukey test (alpha: 5%). DCPD functionalization did not interfere with DC. The composite containing functionalized DCPD showed significantly lower WS and SL in comparison with the material formulated with nonfunctionalized particles. The presence of 10-MDP (as a functionalizing agent or dispersed in the resin phase) reduced the composite's initial BFS and FM. After 5 mo in water, the composite with functionalized DCPD and both glass-only composites were able to maintain their mechanical properties at levels statistically similar to what was observed after 24 h. Ca2+ release was significantly reduced in both formulations containing 10-MDP. In conclusion, DCPD functionalization with 10-MDP increased the composite's resistance to hydrolytic degradation, improving its mechanical stability after prolonged water storage. However, the impaired water transit at the particle-matrix interface led to a reduction in Ca2+ release.


Assuntos
Resinas Compostas , Metacrilatos , Resinas Compostas/química , Teste de Materiais , Metacrilatos/química , Fosfatos de Cálcio/química , Água , Cálcio
3.
Anim Genet ; 52(4): 492-504, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34087001

RESUMO

Brazilian hair sheep constitute a genetic diversity hotspot. These animals are found in the harsh environments of the Brazilian Northwest (semi-arid) region. Genotypes (50K SNP chip) from seven Brazilian sheep breeds (five hair and two coarse wool types) and 87 worldwide breeds were used to test for population structure, admixture and genetic diversity. Moreover, phylogenetic trees evaluating migration events between genetic groups were built. Brazilian Somali, a fat-tailed breed, had a close relationship with East African breeds and clustered distinctly from other Brazilian breeds. Brazilian Blackbelly and Barbados Blackbelly had a close relationship. The Morada Nova breed did not show close relationships with European or African breeds, revealing a single migration event from an Algerian hair breed. Brazilian Fat-tail and Morada Nova share a common ancestor, but the former showed introgressions from Brazilian Somali and Afrikaner breeds, explaining the fat-tail phenotype. The Santa Inês breed received a substantial contribution from Brazilian Bergamasca and showed an admixed origin with recent introgressions from other breeds, mainly from Suffolk. Furthermore, Brazilian Somali and Brazilian Fat-tail are the most endangered sheep genetic resources in Brazil and should be the focus for ex situ conservation programs. In conclusion, Brazilian hair sheep show an African origin and are characterized by diverse genetic composition, reinforcing the need for conservation of these genetic resources, and at the same time, this highly diverse group has variability that can be used in breeding programs.


Assuntos
Pelo Animal , Cruzamento , Genoma , Genótipo , Carneiro Doméstico/genética , Pelo Animal/fisiologia , Animais , Brasil , Filogenia
4.
J Helminthol ; 94: e97, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679527

RESUMO

Several factors influence the dynamics and structure of parasite communities. Our goal was to investigate how the community composition, prevalence and abundance of parasites change across seven populations of the exotic lizard Hemidactylus mabouia in Northeast Brazil, and to describe ontogenetic and sex variations. We found differences in the composition of component communities and patterns of infection according to the host body size across the lizard populations. We did not find any variation between the sexes regarding epidemiological patterns, which can probably be explained by the similar diet and habitat use of male and female H. mabouia. An unusually high abundance and prevalence of trematodes infecting this host lizard was apparent when we compared other native lizard hosts, and we suggest that local environmental conditions might be advantageous to the development and life cycle of these parasites due to the abundance of all the intermediate and definitive hosts.


Assuntos
Lagartos/parasitologia , Parasitos/isolamento & purificação , Doenças Parasitárias em Animais/parasitologia , Animais , Tamanho Corporal , Brasil/epidemiologia , Ecossistema , Feminino , Lagartos/classificação , Lagartos/crescimento & desenvolvimento , Masculino , Parasitos/classificação , Parasitos/genética , Parasitos/fisiologia , Doenças Parasitárias em Animais/epidemiologia
6.
Int J Oral Maxillofac Surg ; 46(5): 662-667, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28233648

RESUMO

This study investigated the antinociceptive effects of (S)-(-)-perillyl alcohol (PA) on orofacial nociception in Swiss male mice using formalin-, capsaicin-, and glutamate-induced pain tests. For each test, eight animals per group were pre-treated intraperitoneally by a blinded investigator with PA (50 or 75mg/kg), morphine, or vehicle (saline+0.2% Tween 80). The treatment was performed before the induction of orofacial nociception by injecting formalin, capsaicin, or glutamate solution into the right area of the upper lip. The orofacial nociceptive behaviour was timed in all tests by an investigator who was blinded to the treatments. The statistical analysis was performed using confidence intervals (CI), the effect size, and power. PA blocked the orofacial nociceptive behaviour at both doses tested (P<0.05) similarly to morphine (P>0.05), in all tests. The effect size was high in the phase 1 formalin test for 50mg/kg PA (95% CI 0.48-2.31, power 84.6%) and 75mg/kg PA (95% CI 0.82-2.76, power 96.2%), in phase 2 for 75mg/kg PA (95% CI 0.44-2.26, power 82.3%), and in the glutamate test for 75mg/kg PA (95% CI 1.11-3.16, power 99.2%). These findings show strong evidence for the antinociceptive properties of PA in the orofacial region.


Assuntos
Dor Facial/tratamento farmacológico , Monoterpenos/farmacologia , Animais , Capsaicina , Formaldeído , Ácido Glutâmico , Masculino , Camundongos , Morfina/farmacologia , Medição da Dor
7.
Vet Parasitol ; 227: 20-5, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27523932

RESUMO

The objective of this paper was to investigate prevalence and parasite load of the trematode Platynosomum fastosum infection and the risk of developing cholangitis/cholangiohepatitis among infected domestic cats in a city of northeastern Brazil, and to characterize the influence of fluke burden in the formation of lesions in liver and gallbladder. A total of 141 cats was necropsied and examined for the presence of P. fastosum. The observed prevalence was 42.6% (60/141, 95% CI=34.2-50.9). Parasite load varied from 1 to 219 flukes per animal. Adult cats were more frequently infected than kittens (p<0.01). Risk of cholangitis was about three times higher in infected animals (RR=3.23, 95% CI=2.01-5.07, p<0.01). Centrolobular congestion, portal cholangitis and cholestasis was significantly more common in infected as compared to non-infected cats (p<0.01). Similarly, fibrosis, cholangitis and mucous gland hyperplasia were significantly more prevalent in the bile duct of infected animals (p<0.01). Mild fibrosis and cholecystitis were observed principally in infected cats. Hyperplastic precursor lesions of cholangiocarcinoma were observed, but no solid tumor was diagnosed. These results reveal high prevalence of P. fastosum in free roaming cats in northeastern Brazil, with increased risk of liver disease.


Assuntos
Doenças do Gato/parasitologia , Trematódeos/classificação , Infecções por Trematódeos/veterinária , Animais , Brasil/epidemiologia , Doenças do Gato/epidemiologia , Gatos , Feminino , Doenças da Vesícula Biliar/epidemiologia , Doenças da Vesícula Biliar/parasitologia , Doenças da Vesícula Biliar/veterinária , Hepatopatias Parasitárias/epidemiologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/veterinária , Masculino , Prevalência , Infecções por Trematódeos/epidemiologia , Infecções por Trematódeos/parasitologia
8.
Genet Mol Res ; 15(1): 15017658, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26985928

RESUMO

We assessed the transferability of 120 EST-derived Eucalyptus microsatellite primers to Campomanesia adamantium and C. pubescens. Both species are berry trees native to the Brazilian Cerrado, and population genetic information is poor. Twelve markers were used to analyze the genetic variability of four sampled populations. Regarding DNA extraction, we sampled leaf tissues from two populations of each species (80 individuals). Of the 120 primers evaluated, 87 did not amplify any PCR products, and 21 rendered nonspecific amplification. Twelve primers were successfully transferred, providing a low combined probability of genetic identity for both species (5.718 x 10(-10) for C. adamantium; 1.182 x 10(-11) for C. pubescens) and a high probability of paternity exclusion (0.99939 for C. adamantium; 0.99982 for C. pubescens). The average number of alleles in the polymorphic loci was 6.8 for C. adamantium and 7.8 for C. pubescens, ranging from 2 to 16 alleles per locus. The observed heterozygosity values for C. adamantium and C. pubescens were 0.504 and 0.503, respectively, and the expected heterozygosity values for C. adamantium and C. pubescens were 0.517 and 0.579, respectively. The populations exhibited structured genetic variability with qP values of 0.105 for C. adamantium and 0.249 for C. pubescens. Thus, we concluded that these 12 microsatellite markers, transferred from Eucalyptus, were efficient for population genetic studies of C. adamantium and C. pubescens.


Assuntos
Variação Genética , Repetições de Microssatélites , Myrtaceae/genética , Alelos , DNA de Plantas , Etiquetas de Sequências Expressas , Genética Populacional
9.
Environ Sci Pollut Res Int ; 22(23): 18987-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26233737

RESUMO

Energetic characterization of biomass allows for assessing its energy potential for application in different conversion processes into energy. The objective of this study is to physicochemically characterize pineapple crown leaves (PC) for their application in energy conversion processes. PC was characterized according to ASTM E871-82, E1755-01, and E873-82 for determination of moisture, ash, and volatile matter, respectively; the fixed carbon was calculated by difference. Higher heating value was determined by ASTM E711-87 and ash chemical composition was determined by XRF. The thermogravimetric and FTIR analyses were performed to evaluate the thermal decomposition and identify the main functional groups of biomass. PC has potential for application in thermochemical processes, showing high volatile matter (89.5%), bulk density (420.8 kg/m(3)), and higher heating value (18.9 MJ/kg). The results show its energy potential justifying application of this agricultural waste into energy conversion processes, implementing sustainability in the production, and reducing the environmental liabilities caused by its disposal.


Assuntos
Ananas/química , Biomassa , Energia Renovável , Agricultura , Carbono/análise , Folhas de Planta/química
10.
Int Endod J ; 48(1): 89-94, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24646329

RESUMO

AIM: To compare the ion release and mechanical properties of a calcium hydroxide (Dycal) and two calcium silicate (MTA Angelus and Biodentine) cements. METHODOLOGY: Calcium and hydroxyl ion release in water from 24-h set cements were calculated from titration with HCl (n = 3). Calcium release after 7, 14, 21 and 28 days at pH 5.5 and 7.0 was measured using ICP-OES (n = 6). Flexural strength (FS) and modulus (E) were tested after 48-h storage, and compressive strength (CS) was tested after 48 h and 7 days (n = 10). Ion release and mechanical data were subjected to anova/Tukey and Kruskal-Wallis/Mann-Whitney tests, respectively (α = 0.05). RESULTS: Titration curves revealed that Dycal released significantly fewer ions in solution than calcium silicates (P < 0.001). Calcium release remained constant at pH 7.0, whilst at pH 5.5, it dropped significantly by 24% after 21 days (P < 0.05). At pH 5.5, MTA Angelus released significantly more calcium than Dycal (P < 0.01), whilst Biodentine had superior ion release than Dycal at pH 7.0 (P < 0.01). Biodentine had superior flexural strength, flexural modulus and compressive strength than the other cements, whilst MTA Angelus had higher modulus than Dycal (P < 0.001). CONCLUSIONS: Immediate calcium and hydroxyl ion release in solution was significantly lower for Dycal. In general, all materials released constant calcium levels over 28 days, but release from Dycal was significantly lower than Biodentine and MTA Angelus depending on pH conditions. Biodentine had substantially higher strength and modulus than MTA Angelus and Dycal, both of which demonstrated low stress-bearing capabilities.


Assuntos
Compostos de Alumínio/química , Compostos de Cálcio/química , Hidróxido de Cálcio/química , Capeamento da Polpa Dentária/métodos , Íons/química , Minerais/química , Óxidos/química , Agentes de Capeamento da Polpa Dentária e Pulpectomia/química , Silicatos/química , Bismuto , Força Compressiva , Análise do Estresse Dentário , Combinação de Medicamentos , Módulo de Elasticidade , Concentração de Íons de Hidrogênio , Espectrofotometria Atômica
11.
Int Endod J ; 48(8): 768-73, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25156123

RESUMO

AIM: To use computerized microtomography (micro-CT) to evaluate the efficacy of passive ultrasonic irrigation (PUI), with or without an additional file (F5), in removing calcium hydroxide medication. METHODOLOGY: The root canals of single-rooted human teeth were prepared with a ProTaper(®) F4 file (Dentsply Maillefer) and filled with calcium hydroxide/propylene glycol 400 paste. After 30 days of storage under 100% humidity, the teeth were divided into four groups (n = 8) according to the removal technique: passive ultrasonic irrigation (PUI) only, additional file only (file F5), PUI + additional file and master apical file only (F4, control). The specimens were scanned (SkyScan 1174, resolution: 14.36 µm) after chemomechanical preparation, 30 days after the application of Ca(OH)2 paste and following its removal. The percentage of medicament remaining was calculated in terms of total canal volume and medicament volume after storage, based on microtomographic images. Data were analysed using three-way anova/Tukey's test or Kruskal-Wallis/Student-Newman-Keuls test (alpha: 5%). RESULTS: The use of PUI resulted in lower Ca(OH)2 residue volumes (3.7%) compared to when PUI was not used (6.4%; P < 0.001). The use of the additional file did not significantly influence the percentage of remaining Ca(OH)2 . The percentage of Ca(OH)2 residue was greater in the apical region (6.4%) than in the cervical region (3.8%; P < 0.01). CONCLUSIONS: The use of PUI resulted in more effective Ca(OH)2 paste removal relative to the control regardless of the use of the additional file. The apical region had the highest residue volumes in all techniques.


Assuntos
Hidróxido de Cálcio/química , Materiais Restauradores do Canal Radicular/química , Irrigação Terapêutica/métodos , Ultrassom , Humanos , Técnicas In Vitro , Propilenoglicol/química , Fatores de Tempo , Microtomografia por Raio-X
12.
Dent Mater ; 30(11): 1274-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25249004

RESUMO

OBJECTIVES: To evaluate conversion, bulk mechanical properties and camphorquinone (CQ) consumption in methacrylate resins, comprising a range of overall initiator concentrations and CQ/amine ratios. METHODS: BisGMA (Bisphenol-A glycidyl dimethacrylate), TEGDMA (triethyleneglycol dimethacrylate) and UDMA (urethane dimethacrylate) were mixed at a 1:1:1 molar ratio. CQ was used as the visible light photosensitizer, in combination with EDMAB (Ethyl p-dimethylamino benzoate), at 3:1, 2:1, 1:1, 1:2 and 1:3 weight ratios, at 0.5, 1.0, 1.5, 2.0 and 3.0 wt% overall initiator concentration. Butylhydroxytoluene was added at 0.05 wt% as an inhibitor. Unfilled resins were photoactivated with a dental light source (VIP Jr, Bisco) for 60 s at 600 mW/cm(2). Flexural strength/modulus were assessed in 2×1×10 mm bars, tested in three-point bending. Degree of conversion was assessed at the bottom of the same specimens using FT-RAMAN. CQ consumption was measured using a UV-vis spectrometer. Data were analyzed with two-way ANOVA/Tukey test (α=5%). RESULTS: Lower conversion and inferior mechanical properties were observed with lower overall initiator concentrations and higher amine/CQ ratios. The lowest overall initiator concentration (0.5%) presented the statistically lowest conversion/properties results, except for the 1:3 amine/CQ ratio. For overall concentrations equal or greater to 1.5%, the amine/CQ ratio did not influence conversion or mechanical properties. CQ consumption was less efficient for the highest overall initiator concentrations and lower amine/CQ ratios. CLINICAL RELEVANCE: Above 1.5 wt% overall initiator concentration, the conversion and general mechanical properties were independent of the initiator concentration. Therefore, there seems to be no benefit to increasing the initiator concentration above that level. At higher camphorquinone concentrations, light transmission and photosensitizer consumption becomes impaired, which could lead to decreased depth of cure and yellowing of the restoration.


Assuntos
Aminas/análise , Cânfora/análogos & derivados , Metacrilatos/química , Cânfora/química , Teste de Materiais , Espectrofotometria Ultravioleta
13.
J Fish Biol ; 85(2): 246-63, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24919949

RESUMO

The diets of six shark species, Sphyrna lewini, Sphyrna zygaena, Carcharhinus obscurus, Carcharhinus limbatus, Rhizoprionodon lalandii and Galeocerdo cuvier, were investigated in a subtropical coastal ecosystem of southern Brazil. Stomach content data were obtained to assess foraging niche segregation and ontogenetic shifts in the diets of these sharks. Five of the shark species off the Paraná coast were ichthyophagous, with the exception of S. zygaena, which was teutophagous. With the exception of G. cuvier, which had a generalist diet, the other five species displayed specialization in their feeding. Ontogenetic shifts were observed in C. obscurus and S. lewini with large individuals consuming elasmobranchs. Owing to the diet overlap between C. obscurus and S. lewini, C. obscurus and C. limbatus and R. lalandii and C. limbatus, future studies on the spatial and temporal distributions of these species are needed to understand the extent of competitive interactions.


Assuntos
Dieta , Cadeia Alimentar , Tubarões , Animais , Brasil , Ecossistema , Comportamento Predatório , Tubarões/classificação , Especificidade da Espécie
14.
Genet Mol Res ; 13(2): 3656-66, 2014 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-24854445

RESUMO

Geographical genetics allows the evaluation of evolutionary processes underlying genetic variation within and among local populations and forms the basis for establishing more effective strategies for biodiversity conservation at the population level. In this study, we used explicit spatial analyses to investigate molecular genetic variation (estimated using 7 microsatellite markers) of Pseudoplatystoma punctifer, by using samples obtained from 15 localities along the Madeira River and Solimões, Amazon Basin. A high genetic diversity was observed associated with a relatively low FST (0.057; P < 0.001), but pairwise FST values ranged from zero up to 0.21 when some pairs of populations were compared. These FST values have a relatively low correlation with geographic distances (r = 0.343; P = 0.074 by Mantel test), but a Mantel correlogram revealed that close populations (up to 80 km) tended to be more similar than expected by chance (r = 0.360; P = 0.015). The correlogram also showed a exponential-like decrease of genetic similarity with distance, with a patch-size of around 200 km, compatible with isolation-by-distance and analogous processes related to local constraints of dispersal and spatially structured levels of gene flow. The pattern revealed herein has important implications for establishing strategies to maintain genetic diversity in the species, especially considering the threats due to human impacts caused by building large dams in this river system.


Assuntos
Evolução Biológica , Peixes-Gato/genética , Conservação dos Recursos Naturais , Filogeografia , Animais , Variação Genética , Genética Populacional , Humanos , Rios
15.
Ann Bot ; 113(3): 555-63, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24284818

RESUMO

BACKGROUND AND AIMS: Shining a laser onto biological material produces light speckles termed biospeckles. Patterns of biospeckle activity reflect changes in cell biochemistry, developmental processes and responses to the environment. The aim of this work was to develop methods to investigate the biospeckle activity in roots and to characterize the distribution of its intensity and response to thigmostimuli. METHODS: Biospeckle activity in roots of Zea mays, and also Jatropha curcas and Citrus limonia, was imaged live and in situ using a portable laser and a digital microscope with a spatial resolution of 10 µm per pixel and the ability to capture images every 0.080 s. A procedure incorporating a Fujii algorithm, image restoration using median and Gaussian filters, image segmentation using maximum-entropy threshold methods and the extraction of features using a tracing algorithm followed by spline fitting were developed to obtain quantitative information from images of biospeckle activity. A wavelet transform algorithm was used for spectral decomposition of biospeckle activity and generalized additive models were used to attribute statistical significance to changes in patterns of biospeckle activity. KEY RESULTS: The intensity of biospeckle activity was greatest close to the root apex. Higher frequencies (3-6 Hz) contributed most to the total intensity of biospeckle activity. When a root encountered an obstacle, the intensity of biospeckle activity decreased abruptly throughout the root system. The response became attenuated with repeated thigmostimuli. CONCLUSIONS: The data suggest that at least one component of root biospeckle activity resulted from a biological process, which is located in the zone of cell division and responds to thigmostimuli. However, neither individual cell division events nor root elongation is likely to be responsible for the patterns of biospeckle activity.


Assuntos
Citrus/citologia , Processamento de Imagem Assistida por Computador/métodos , Jatropha/citologia , Lasers , Zea mays/citologia , Algoritmos , Citrus/metabolismo , Citrus/efeitos da radiação , Jatropha/metabolismo , Jatropha/efeitos da radiação , Microscopia , Raízes de Plantas/citologia , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos da radiação , Espalhamento de Radiação , Zea mays/metabolismo , Zea mays/efeitos da radiação
16.
Mini Rev Med Chem ; 12(6): 573-82, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22587770

RESUMO

In modern drug discovery process, ADME/Tox properties should be determined as early as possible in the test cascade to allow a timely assessment of their property profiles. To help medicinal chemists in designing new compounds with improved pharmacokinetics, the knowledge of the soft spot position or the site of metabolism (SOM) is needed. In recent years, large number of in silico approaches for metabolism prediction have been developed and reported. Among these methods, QSAR models and combined quantum mechanics/molecular mechanics (QM/MM) methods for predicting drug metabolism have undergone significant advances. This review provides a perspective of the utility of QSAR and QM/MM approaches on drug metabolism prediction, highlighting the present challenges, limitations, and future perspectives in medicinal chemistry.


Assuntos
Preparações Farmacêuticas/metabolismo , Relação Quantitativa Estrutura-Atividade , Teoria Quântica , Farmacocinética
17.
Eur J Pharm Biopharm ; 79(1): 189-96, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21352915

RESUMO

Topotecan is an important cytotoxic drug that has gained broad acceptance in clinical use for the treatment of refractory ovarian and small-cell lung cancer. The lactone active form of topotecan can be hydrolyzed in vivo, decreasing the drug's therapeutic efficacy. Lipid encapsulation may promote in vivo stabilization by removing topotecan from aqueous media. Earlier reports of topotecan lipid nanoencapsulation have focused on liposomal encapsulation; however, the higher stability and cost-effectiveness of solid lipid nanoparticles (SLN) highlight the potential of these nanoparticles as an advantageous carrier for topotecan. The initial motivation for this work was to develop, for the first time, solid lipid nanoparticles and nanostructured lipid carriers (NLC) with a high drug loading for topotecan. A microemulsion technique was employed to prepare SLNs and NLCs and produced homogeneous, small size, negatively charged lipid nanoparticles with high entrapment efficiency and satisfactory drug loading. However, low recovery of topotecan was observed when the microemulsion temperature was high and in order to obtain high quality nanoparticles, and precise control of the microemulsion temperature is critical. Nanoencapsulation sustained topotecan release and improved its chemical stability and cytotoxicity. Surprisingly, there were no significant differences between the NLCs and SLNs, and both are potential carriers for topotecan delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Inibidores da Topoisomerase I/química , Topotecan/química , Sobrevivência Celular/fisiologia , Preparações de Ação Retardada , Portadores de Fármacos/química , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Emulsões/química , Liofilização , Humanos , Células K562 , Lipídeos/química , Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Nanoestruturas/análise , Nanoestruturas/química , Nanoestruturas/toxicidade , Tamanho da Partícula , Solubilidade , Propriedades de Superfície , Temperatura , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/toxicidade , Topotecan/administração & dosagem , Topotecan/metabolismo , Topotecan/toxicidade , Azul Tripano
18.
J Dent Res ; 90(3): 365-70, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21098474

RESUMO

The literature shows contradictory results regarding the role of composite shrinkage and elastic modulus as determinants of polymerization stress. The present study aimed at a better understanding of the test mechanics that could explain such divergences among studies. The hypothesis was that the effects of composite shrinkage and elastic modulus on stress depend upon the compliance of the testing system. A commonly used test apparatus was simulated by finite element analysis, with different compliance levels defined by the bonding substrate (steel, glass, composite, or acrylic). Composites with moduli between 1 and 12 GPa and shrinkage values between 0.5% and 6% were modeled. Shrinkage was simulated by thermal analogy. The hypothesis was confirmed. When shrinkage and modulus increased simultaneously, stress increased regardless of the substrate. However, if shrinkage and modulus were inversely related, their magnitudes and interaction with rod material determined the stress response.


Assuntos
Resinas Compostas/química , Análise do Estresse Dentário/métodos , Teste de Materiais/métodos , Complacência (Medida de Distensibilidade) , Análise do Estresse Dentário/instrumentação , Módulo de Elasticidade , Análise de Elementos Finitos , Teste de Materiais/instrumentação , Estresse Mecânico , Temperatura de Transição
19.
J Dent Res ; 89(12): 1499-504, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20940353

RESUMO

The long-term effectiveness of chlorhexidine as a matrix metalloproteinase (MMP) inhibitor may be compromised when water is incompletely removed during dentin bonding. This study challenged this anti-bond degradation strategy by testing the null hypothesis that wet-bonding with water or ethanol has no effect on the effectiveness of chlorhexidine in preventing hybrid layer degradation over an 18-month period. Acid-etched dentin was bonded under pulpal pressure simulation with Scotchbond MP and Single Bond 2, with water wet-bonding or with a hydrophobic adhesive with ethanol wet-bonding, with or without pre-treatment with chlorhexidine diacetate (CHD). Resin-dentin beams were prepared for bond strength and TEM evaluation after 24 hrs and after aging in artificial saliva for 9 and 18 mos. Bonds made to ethanol-saturated dentin did not change over time with preservation of hybrid layer integrity. Bonds made to CHD pre-treated acid-etched dentin with commercial adhesives with water wet-bonding were preserved after 9 mos but not after 18 mos, with severe hybrid layer degradation. The results led to rejection of the null hypothesis and highlight the concept of biomimetic water replacement from the collagen intrafibrillar compartments as the ultimate goal in extending the longevity of resin-dentin bonds.


Assuntos
Colagem Dentária/métodos , Adesivos Dentinários/química , Etanol/química , Solventes/química , Condicionamento Ácido do Dente , Bis-Fenol A-Glicidil Metacrilato/química , Clorexidina/química , Clorexidina/farmacologia , Colágeno/ultraestrutura , Resinas Compostas/química , Materiais Dentários/química , Análise do Estresse Dentário/instrumentação , Dentina/ultraestrutura , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Inibidores de Metaloproteinases de Matriz , Microscopia Eletrônica de Transmissão , Cimentos de Resina/química , Saliva Artificial/química , Estresse Mecânico , Fatores de Tempo , Água/química
20.
Dent Mater ; 26(7): 704-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20378161

RESUMO

OBJECTIVES: The role of inorganic content on physical properties of resin composites is well known. However, its influence on polymerization stress development has not been established. The aim of this investigation was to evaluate the influence of inorganic fraction on polymerization stress and its determinants, namely, volumetric shrinkage, elastic modulus and degree of conversion. METHODS: Eight experimental composites containing 1:1 BisGMA (bisphenylglycidyl dimethacrylate):TEGDMA (triethylene glycol dimethacrylate) (in mol) and barium glass at increasing concentrations from 25 to 60 vol.% (5% increments) were tested. Stress was determined in a universal test machine using acrylic as bonding substrate. Nominal polymerization stress was obtained diving the maximum load by the cross-surface area. Shrinkage was measured using a water picnometer. Elastic modulus was obtained by three-point flexural test. Degree of conversion was determined by FT-Raman spectroscopy. RESULTS: Polymerization stress and shrinkage showed inverse relationships with filler content (R(2)=0.965 and R(2)=0.966, respectively). Elastic modulus presented a direct correlation with inorganic content (R(2)=0.984). Degree of conversion did not vary significantly. Polymerization stress showed a strong direct correlation with shrinkage (R(2)=0.982) and inverse with elastic modulus (R(2)=0.966). SIGNIFICANCE: High inorganic contents were associated with low polymerization stress values, which can be explained by the reduced volumetric shrinkage presented by heavily filled composites.


Assuntos
Resinas Compostas/química , Adaptação Marginal Dentária , Análise de Variância , Compostos de Bário , Bis-Fenol A-Glicidil Metacrilato , Resinas Compostas/efeitos da radiação , Análise do Estresse Dentário , Módulo de Elasticidade , Dureza , Compostos Inorgânicos , Cura Luminosa de Adesivos Dentários , Teste de Materiais , Tamanho da Partícula , Transição de Fase , Maleabilidade , Polietilenoglicóis , Ácidos Polimetacrílicos , Análise de Regressão , Dióxido de Silício , Espectroscopia de Infravermelho com Transformada de Fourier
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