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1.
Mol Biol Evol ; 40(1)2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36585846

RESUMO

Escherichia coli have served as important model organisms for over a century-used to elucidate key aspects of genetics, evolution, molecular biology, and pathogenesis. However, defining which strains actually belong to this species is erratic and unstable due to shifts in the characters and criteria used to distinguish bacterial species. Additionally, many isolates designated as E. coli are genetically more closely related to strains of Shigella than to other E. coli, creating a situation in which the entire genus of Shigella and its four species are encompassed within the single species E. coli. We evaluated all complete genomes assigned to E. coli and its closest relatives according to the biological species concept (BSC), using evidence of reproductive isolation and gene flow (i.e., homologous recombination in the case of asexual bacteria) to ascertain species boundaries. The BSC establishes a uniform, consistent, and objective principle that allows species-level classification across all domains of life and does not rely on either phenotypic or genotypic similarity to a defined type-specimen for species membership. Analyzing a total of 1,887 sequenced genomes and comparing our results to other genome-based classification methods, we found few barriers to gene flow among the strains, clades, phylogroups, or species within E. coli and Shigella. Due to the utility in recognizing which strains constitute a true biological species, we designate genomes that form a genetic cohesive group as members of E. coliBIO.


Assuntos
Escherichia coli , Shigella , Escherichia coli/genética , Filogenia , Shigella/genética , Genoma , Sequência de Bases , Genoma Bacteriano
2.
Medicina (Kaunas) ; 60(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38541136

RESUMO

Background and Objectives: The purpose of this study to investigate if the early variations in the hematological profile could be a useful tool in the prediction and evaluation of intraventricular hemorrhage. Materials and Methods: It is a retrospective study conducted between 1 January 2017 and 31 December 2022, in a tertiary academic center. In-born infants ≤ 28 weeks of gestation (n = 134) were enrolled. The study group of infants with all grades of IVH was further divided into mild IVH subgroups (grades 1 and 2) and severe IVH subgroups (grades 3 and 4); the control group included infants without IVH. Results: The prevalence of IVH was 35.8% (n = 48 of 134 infants-study group). We identified significantly lower median values of HGB (p = 0.0312) and HCT (p = 0.0172) in all grades of the IVH group at birth as compared with control, followed by a significantly higher drop in MCV (p = 0.0146) and MCH (p = 0.0002) in the fourth day of life. Conclusions: Extremely preterm infants with IVH may have lower HTC and HGB values at birth, together with a decrease in MCH and MCHC and increase in MPV. The predictive model based on logistic regression analysis could predict the probability of the occurrence of IVH according to their values.


Assuntos
Hemorragia Cerebral , Lactente Extremamente Prematuro , Lactente , Recém-Nascido , Humanos , Estudos Retrospectivos , Idade Gestacional , Fatores de Risco , Hemorragia Cerebral/epidemiologia
3.
BMC Genomics ; 20(1): 960, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823721

RESUMO

BACKGROUND: Metagenomes can be analysed using different approaches and tools. One of the most important distinctions is the way to perform taxonomic and functional assignment, choosing between the use of assembly algorithms or the direct analysis of raw sequence reads instead by homology searching, k-mer analysys, or detection of marker genes. Many instances of each approach can be found in the literature, but to the best of our knowledge no evaluation of their different performances has been carried on, and we question if their results are comparable. RESULTS: We have analysed several real and mock metagenomes using different methodologies and tools, and compared the resulting taxonomic and functional profiles. Our results show that database completeness (the representation of diverse organisms and taxa in it) is the main factor determining the performance of the methods relying on direct read assignment either by homology, k-mer composition or similarity to marker genes, while methods relying on assembly and assignment of predicted genes are most influenced by metagenomic size, that in turn determines the completeness of the assembly (the percentage of read that were assembled). CONCLUSIONS: Although differences exist, taxonomic profiles are rather similar between raw read assignment and assembly assignment methods, while they are more divergent for methods based on k-mers and marker genes. Regarding functional annotation, analysis of raw reads retrieves more functions, but it also makes a substantial number of over-predictions. Assembly methods are more advantageous as the size of the metagenome grows bigger.


Assuntos
Biologia Computacional/métodos , Metagenoma/genética , Anotação de Sequência Molecular/métodos , Algoritmos , Análise por Conglomerados , Metagenômica , Análise de Sequência de DNA
4.
BMC Genomics ; 18(1): 499, 2017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28662636

RESUMO

BACKGROUND: Despite the important role that microorganisms play in environmental processes, the low percentage of cultured microbes (5%) has limited, until now, our knowledge of their ecological strategies. However, the development of high-throughput sequencing has generated a huge amount of genomic and metagenomic data without the need of culturing that can be used to study ecological questions. This study aims to estimate the functional capabilities, genomic sizes and 16S copy number of different taxa in relation to their ubiquity and their environmental preferences. RESULTS: To achieve this goal, we compiled data regarding the presence of each prokaryotic genera in diverse environments. Then, genomic characteristics such as genome size, 16S rRNA gene copy number, and functional content of the genomes were related to their ubiquity and different environmental preferences of the corresponding taxa. The results showed clear correlations between genomic characteristics and environmental conditions. CONCLUSIONS: Ubiquity and adaptation were linked to genome size, while 16S copy number was not directly related to ubiquity. We observed that different combinations of these two characteristics delineate the different environments. Besides, the analysis of functional classes showed some clear signatures linked to particular environments.


Assuntos
Meio Ambiente , Genômica , Microbiologia , Bases de Dados Genéticas
5.
PLoS Biol ; 12(2): e1001799, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24586114

RESUMO

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk.


Assuntos
Tamanho Corporal/genética , Proteína Adaptadora GRB10/genética , Animais , Feminino , Proteína Adaptadora GRB10/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , Carioferinas/fisiologia , Lactação/genética , Camundongos , Camundongos Knockout , Receptores Citoplasmáticos e Nucleares/fisiologia , Fator de Transcrição STAT5/fisiologia , Proteína Exportina 1
6.
Mol Phylogenet Evol ; 97: 155-169, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26785110

RESUMO

Southern Iberian freshwater ecosystems located at the border between the European and African plates represent a tectonically complex region spanning several geological ages, from the uplifting of the Betic Mountains in the Serravalian-Tortonian periods to the present. This area has also been subjected to the influence of changing climate conditions since the Middle-Upper Pliocene when seasonal weather patterns were established. Consequently, the ichthyofauna of southern Iberia is an interesting model system for analyzing the influence of Cenozoic tectonic and climatic events on its evolutionary history. The cyprinids Squalius malacitanus and Squalius pyrenaicus are allopatrically distributed in southern Iberia and their evolutionary history may have been defined by Cenozoic tectonic and climatic events. We analyzed MT-CYB (510 specimens) and RAG1 (140 specimens) genes of both species to reconstruct phylogenetic relationships and to estimate divergence times and ancestral distribution ranges of the species and their populations. We also assessed their levels of genetic structure and diversity as well as the amount of gene flow between populations. To investigate recent paleogeographical and climatic factors in southern Iberia, we modeled changes-through-time in sea level from the LGM to the present. Phylogenetic, geographic and population structure analyses revealed two well-supported species (S. malacitanus and S. pyrenaicus) in southern Iberia and two subclades (Atlantic and Mediterranean) within S. malacitanus. The origin of S. malacitanus and the separation of its Atlantic and Mediterranean populations occurred during the Serravalian-Tortonian and Miocene-Pliocene periods, respectively. These divergence events occurred in the Middle Pliocene and Pleistocene in S. pyrenaicus. In both species, Atlantic basins possessed populations with higher genetic diversity than Mediterranean, which may be explained by the Janda Lagoon. The isolation of S. malacitanus was earlier and related to the rising of the Betic Mountains. Divergence of its Atlantic and Mediterranean populations was associated with the creation of the freshwater systems of southern Iberia close to the Gibraltar Strait. The presence of S. pyrenaicus in southern Iberia may be the result of recent colonization associated with river capture, as demonstrated our biogeographic reconstruction.


Assuntos
Clima , Cyprinidae/genética , Ecossistema , Água Doce , Filogenia , Animais , Oceano Atlântico , Evolução Molecular , Fluxo Gênico/genética , Genes Mitocondriais/genética , Variação Genética , História Antiga , Mar Mediterrâneo , Filogeografia , Rios , Espanha
7.
BMC Biol ; 12: 771, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25551289

RESUMO

BACKGROUND: Despite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that the insulin-like growth factor (IGF) pathway has a central role in growth regulation, probably in all animals. The involvement of imprinted genes has also attracted much attention, not least because two of the earliest discovered were shown to be oppositely imprinted and antagonistic in their regulation of growth. The Igf2 gene encodes a paternally expressed ligand that promotes growth, while maternally expressed Igf2r encodes a cell surface receptor that restricts growth by sequestering Igf2 and targeting it for lysosomal degradation. There are now over 150 imprinted genes known in mammals, but no other clear examples of antagonistic gene pairs have been identified. The delta-like 1 gene (Dlk1) encodes a putative ligand that promotes fetal growth and in adults restricts adipose deposition. Conversely, Grb10 encodes an intracellular signalling adaptor protein that, when expressed from the maternal allele, acts to restrict fetal growth and is permissive for adipose deposition in adulthood. RESULTS: Here, using knockout mice, we present genetic and physiological evidence that these two factors exert their opposite effects on growth and physiology through a common signalling pathway. The major effects are on body size (particularly growth during early life), lean:adipose proportions, glucose regulated metabolism and lipid storage in the liver. A biochemical pathway linking the two cell signalling factors remains to be defined. CONCLUSIONS: We propose that Dlk1 and Grb10 define a mammalian growth axis that is separate from the IGF pathway, yet also features an antagonistic imprinted gene pair.


Assuntos
Desenvolvimento Fetal/genética , Proteína Adaptadora GRB10/genética , Impressão Genômica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Absorciometria de Fóton , Tecido Adiposo/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Proliferação de Células , Feminino , Fibroblastos/metabolismo , Fase G2 , Proteína Adaptadora GRB10/metabolismo , Teste de Tolerância a Glucose , História Antiga , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tamanho do Órgão , Fase S , Triglicerídeos/sangue
8.
J Clin Med ; 13(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38398420

RESUMO

BACKGROUND: Adequate perinatal management is essential in caring for extremely preterm (EP) infants. We aimed to evaluate and compare the impact of different protocols on short-term outcomes. METHODS: A retrospective study was conducted on EP infants in a Romanian perinatal tertiary center during 2008-2012 and 2018-2022. RESULTS: Data on 270 EP infants (121 in period I, 149 in period II) were analyzed collectively and stratified into two subgroups by gestational age. Initial FiO2 administration (100% vs. 40%% p < 0.001), lung recruitment at birth (19.0% vs. 55.7% p < 0.001), early rescue surfactant administration (34.7% vs. 65.8%; p < 0.001), and the mechanical ventilation rate (98.3% vs. 58.4%; p < 0.001) were significantly improved during period II. Survival rates of EP infants significantly improved from 41.3% to 72.5%, particularly in the 26-28 weeks subgroup (63.8% to 83%). Compared to period I, the overall frequency of severe IVH decreased in period II from 30.6% to 14.1%; also, BPD rates were lower (36.6% vs. 23.4%; p = 0.045) in the 26-28 weeks subgroup. Despite improvements, there were no significant differences in the frequencies of NEC, sepsis, PVL, ROP, or PDA. CONCLUSIONS: Implementing evidence-based clinical guidelines can improve short-term outcomes.

9.
Biomedicines ; 12(6)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38927343

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤ 32 weeks of gestational age (GA) within 24 h of birth. MATERIALS AND METHODS: It is a prospective study conducted from 1 March 2022 to 31 December 2023 in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n = 44) and non-surfactant (n = 44) subgroups. RESULTS: A total of 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler score at 24 h of life (1 - RR = 1 - 0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p = 0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p = 0.0178), pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p = 0.0210), and post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p = 0.0336). There were no significant changes in ductus arteriosus parameters at 24 h of life. CONCLUSIONS: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤ 32 weeks of gestational age at 24 h of life.

10.
Biomedicines ; 12(9)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39335532

RESUMO

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO2 and crSO2.

11.
J Crit Care Med (Targu Mures) ; 10(1): 19-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39108797

RESUMO

Introduction: This study is part of a European survey on delivery room practices endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Romanian Association of Neonatology (ANR). The aim of our study was to evaluate the current neonatal resuscitation practices in Romanian maternity hospitals and to compare the results between level III and level II centers. Material and Methods: The questionnaire was distributed through ANR by email link to heads of neonatal departments of 53 Romanian maternity hospitals with more than one thousand of births per year between October 2019 and September 2020, having 2018 as the reference year for data collection. Results: The overall response rate to the questionnaire was 62.26% (33/53), 83.33% (15/18) for level-III centers and 51.43% (18/35) for level-II centers. Of the responding centers, 18 (54,54%) were academic hospitals, 15 (83,33%) were level III and 3 (16,67%) level II hospitals. In 2018, responding centers reported 81.139 births representing 42.66% of all Romanian births (190.170). There were significant differences between level-III and level-II maternity hospitals regarding the number of births in 2018 (3028.73±1258.38 vs 1983.78±769.99; P=0.006), lowest GA of routinely assisted infants in delivery room (25.07±3.03 weeks vs 30.44±3.28, P<0.001), inborn infants with BW<1500 admitted to neonatal intensive care unit (NICU) in 2018 (66.86±39.14 g vs 22.87±31.50 g; P=0.002), and antenatal counseling of parents before the delivery of a very preterm infant or an infant with expected problems (60% vs 22.2%; P=0.027). There were no significant differences of thermal and umbilical cord management, positive pressure delivery, heart rate assessment between responding centers. Conclusion: The adherence to new guidelines was high among responding centers regarding thermal and umbilical cord management, initial FiO2, but aspects like antenatal counseling, EKG monitoring, laryngeal mask, and heated/humidified gases availability and administration, and simulation-based training require further implementation.

12.
Healthcare (Basel) ; 11(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36767013

RESUMO

BACKGROUND: It is currently considered that early initiation of nasal continuous positive airway pressure, using a less invasive exogenous surfactant administration and avoiding mechanical ventilation as much as possible to minimize lung damage, may reduce mortality and/or the risk of morbidities in preterm infants. The aim of our study was to quantify our experience and compare different strategies of surfactant administration, to investigate which method is associated with less morbidity. MATERIALS AND METHODS: A total of 135 preterm infants with early rescue surfactant administration for respiratory distress syndrome were included in the study. The infants were treated in an academic, Level III Neonatal Intensive Care Unit over a 3-year period between 1 December 2018 and 1 December 2021. Patients were separated into three groups: those with standard surfactant administration; those with Less Invasive Surfactant Administration-LISA; and those with Intubation Surfactant Administration Extubation-INSURE. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 h, while the secondary outcomes were major neonatal morbidities and death before discharge. RESULTS: The surfactant administration method was significantly associated with the need for mechanical ventilation within 72 h after the procedure (p < 0.001). LISA group infants needed less MV (OR = 0.538, p = 0.019) than INSURE group infants. We found less morbidities (OR = 0.492, p = 0.015) and deaths before discharge (OR = 0.640, p = 0.035) in the LISA group compared with the INSURE group. The analysis of morbidities found in infants who were given the surfactant by the LISA method compared with the INSURE method showed lower incidence of pneumothorax (3.9% vs. 8.8%), intraventricular hemorrhage (17.3% vs. 23.5%), intraventricular hemorrhage grade 3 and 4 (3.9% vs. 5.9%), sepsis/probable sepsis (11.5% vs. 17.7%) retinopathy of prematurity (16.7% vs. 26.7%) and deaths (3.9% vs. 5.9%). There were no significant differences between groups in frequencies of bronchopulmonary dysplasia, necrotizing enterocolitis and patent ductus arteriosus. CONCLUSIONS: Less invasive surfactant administration methods seem to have advantages regarding early need for mechanical ventilation, decreasing morbidities and death rate. In our opinion, the LISA procedure may be a good choice in spontaneously breathing infants regardless of gestational age.

13.
mSystems ; 8(4): e0029223, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37486130

RESUMO

The genus Salmonella comprises two species, Salmonella bongori and Salmonella enterica, which are infectious to a wide variety of animal hosts. The diversity within S. enterica has been further partitioned into 6-10 subspecies based on such features as host range, geography, and most recently, genetic relatedness and phylogenetic affiliation. Although Salmonella pathogenicity is attributable to large numbers of acquired virulence factors, the extent of homologous exchange in the species at large is apparently constrained such that the species and subspecies form distinct clusters of strains. To explore the extent of gene flow within and among subspecies, and to ultimately define true biological species, we evaluated patterns of recombination in over 1,000 genomes currently assigned to the genus. Those Salmonella subspecies containing sufficient numbers of sequenced genomes to allow meaningful analysis-i.e., subsp. enterica and diarizonae-were found to be reproductively isolated from one another and from all other subspecies. Based on the configuration of genomic sequence divergence among subspecies, it is expected that each of the other Salmonella subspecies will also represent a biological species. Our findings argue against the application of prescribed nucleotide-identity thresholds to delineate bacterial species and contend that the Biological Species Concept should not be disregarded for bacteria, even those, like Salmonella, that demonstrate complex patterns of species and subspecies divergence. IMPORTANCE The Biological Species Concept (BSC), which defines species boundaries based on the capacity for gene exchange, is widely used to classify sexually reproducing eukaryotes but is generally thought to be inapplicable to bacteria due to their completely asexual mode of reproduction. We show that the genus Salmonella, whose thousands of described serovars were formerly considered to be strictly clonal, undergoes sufficient levels of homologous recombination to be assigned to species according to the BSC. Aside from the two recognized species, Salmonella enterica and Salmonella bongori, several (and likely all) of the subspecies within S. enterica are reproductively isolated from one another and should each be considered a separate biological species. These findings demonstrate that species barriers in bacteria can form despite high levels of nucleotide identity and that commonly applied thresholds of genomic sequence identity are not reliable indicators of bacterial species status.


Assuntos
Fluxo Gênico , Salmonella enterica , Animais , Filogenia , Salmonella/genética , Salmonella enterica/genética , Nucleotídeos
14.
Pharmaceutics ; 15(2)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36839731

RESUMO

(1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was the bioequivalent for Cmax, AUC0-t and AUC0-inf, in the single-dose study; (2) Methods: a cross-over study was performed in 36 subjects receiving desvenlafaxine 100 mg prolonged-release tablets. Conventional (Cmax, AUC0-t and AUC0-inf) and additional (Cτ, pAUCs and HVD) PK metrics were considered after single-dose conditions. Predicted PK metrics at steady state (AUC0-τ, Cmax,ss, and Cτ,ss) were derived using a population PK model approach; (3) Results: the existing differences in the shape of the concentration-time curves precluded to show equivalence for Cτ,ss in the simulated study at steady state. This failure to show equivalence at steady state was predicted by Cτ, pAUCs and HVD in the single-dose study. Cτ was the most sensitive metric for detecting the different shape, with a lower intra-subject variability than HVD; (4) Conclusions: conventional PK metrics for single-dose studies (Cmax, AUC0-t and AUC0-inf) are not enough to guarantee bioequivalence at steady state for prolonged-release products.

15.
Eur J Clin Pharmacol ; 68(7): 1043-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22294059

RESUMO

PURPOSE: The aim of this study was to compare the systemic exposure of lercanidipine (Zanidip) after oral administration in the fasted state and 15 min before food intake (meals) to investigate if the recommendations in the Summary of Product Characteristics (SPC) with respect to the intake of meals are adequate. METHODS: The results of three pilot bioequivalence studies performed to develop a lercanidipine generic product, where Zanidip was administered consistently as reference product in the fasted state or 15 min before a standard breakfast, were compared to estimate the drug­food interaction and the similarity of the methods of administration defined in the SPC. RESULTS: The ingestion of a standard (non-high-fat, non-high-calorie) meal 15 min after drug intake increased the area under the concentration­time curve (AUC(0-t)) of S-lercanidipine by 1.78-fold [90% confidence interval (CI) 1.48­2.15, P<0.0001] and the maximum concentration (Cmax) of Slercanidipine by 1.82-fold (90% CI 1.46­2.28, P<0.0001). These values are close to the twofold increase that has been described when Zanidip was taken immediately after a carbohydrate-rich meal. Higher levels would be expected with a high-fat, high-calorie meal. CONCLUSIONS: As intake with a carbohydrate-rich meal is not recommended in the SPC of Zanidip because a twofold difference was considered to be clinically relevant, the intake of lercanidipine only 15 min before food intake does not seem to be consistent with this recommendation. The Marketing Authorisation Holder should clarify the dosing instructions in relation to meals and identify a sufficient time-lapse to ensure an exposure similar to that obtained in phase III clinical efficacy studies.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacocinética , Di-Hidropiridinas/administração & dosagem , Di-Hidropiridinas/farmacocinética , Rotulagem de Medicamentos , Interações Alimento-Droga , Área Sob a Curva , Bloqueadores dos Canais de Cálcio/sangue , Bloqueadores dos Canais de Cálcio/química , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Interpretação Estatística de Dados , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Di-Hidropiridinas/sangue , Di-Hidropiridinas/química , Esquema de Medicação , Ingestão de Alimentos , Jejum , Feminino , Humanos , Masculino , Projetos Piloto , Estereoisomerismo , Equivalência Terapêutica , Fatores de Tempo
16.
Toxics ; 9(8)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34437503

RESUMO

Studies that evaluate the impact of microplastic particles (MPs) often apply particles of pristine material. However, MPs are affected by various abiotic and biotic processes in the environment that possibly modify their physical and chemical characteristics, which might then result in their altered toxic effect. This study evaluated the consequence of weathering on the release of toxic leachates from microplastics. MPs derived from six marine antifouling paints, end-of-life tires, and unplasticised PVC were exposed to UV-C radiation to simulate weathering. Non-weathered and weathered MPs were leached in algae growth medium for 72 h to demonstrate additive release under freshwater conditions. The model organism, green algae Raphidocelis subcapitata, was exposed to the resulting leachates of both non-weathered and weathered MPs. The results of the growth inhibition tests showed that the leachates of weathered microparticles were more toxic than of the non-weathered material, which was reflected in their lower median effect concentration (EC50) values. Chemical analysis of the leachates revealed that the concentration of heavy metals was several times higher in the leachates of the weathered MPs compared to the non-weathered ones, which likely contributed to the increased toxicity. Our findings suggest including weathered microplastic particles in exposure studies due to their probably differing impact on biota from MPs of pristine materials.

17.
Chemosphere ; 274: 129749, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33540312

RESUMO

Microplastics prepared from commercial marine antifouling paints were weathered by UV-C irradiation representing between 25 and 101 days of real-time, outdoor exposure. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy of the degraded paint particles showed that weathering induced chemical changes in the material, including the release of volatile components and the formation of hydrophilic groups. The chemical changes and increased reactivity of the paint binder were associated with alterations in their physical properties and increased leaching of metals in freshwater conditions. Changes in the spectra obtained from weathered paint samples reduced their match with spectra of unaged materials, resulting in a poorer similarity index, the Score when using automatic identification tools for microplastics. The results suggest that spectra of weathered, as well as pristine paint microplastics, should be consulted when applying analytical pipelines to identify microplastics extracted from natural matrices.


Assuntos
Microplásticos , Poluentes Químicos da Água , Pintura , Plásticos , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
18.
Front Cell Dev Biol ; 9: 676543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239874

RESUMO

Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.

19.
Ideggyogy Sz ; 63(5-6): 193-6, 2010 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-20648784

RESUMO

Aspergillus infection of the central nervous system is a rare disease, occasionally seen among immunocompromised patients. The most frequent pathway is hematogenic dissemination. Less known is the direct propagation from the paranasal sinuses, which is usually observed in immunocompetent patients. We report a patient who developed cavernous sinus syndrome due to an invasive intracranial aspergilloma after longlasting chemo- and steroid therapy for chronic lymphoid leukemia and immunhemolytic anemia. The characteristic features seen on radiological images--brain CT and MRI--suggested the possibility of invasive aspergilloma. Postoperative histology defined the diagnosis. Our case review highlights the importance of considering the possibility of an invasive opportunistic infection of the CNS in an immunocompromised patient presenting a new neurological sign.


Assuntos
Seio Cavernoso , Hospedeiro Imunocomprometido , Neuroaspergilose/diagnóstico por imagem , Neuroaspergilose/patologia , Idoso , Seio Cavernoso/parasitologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Neuroaspergilose/cirurgia , Síndrome , Tomografia Computadorizada por Raios X
20.
Appl Spectrosc ; 74(9): 1127-1138, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32193948

RESUMO

Microplastics (MP) are ubiquitous within the environment, but the approaches to analysis of this contaminant are currently quite diverse, with a number of analytical methods available. The comparability of results is hindered as even for a single analytical method such as Fourier transform infrared spectroscopy (FT-IR) the different instruments currently available do not allow a harmonized analysis. To overcome this limitation, a new free of charge software tool, allowing the systematic identification of MP in the environment (siMPle) was developed. This software tool allows a rapid and harmonized analysis of MP across FT-IR systems from different manufacturers (Bruker Hyperion 3000, Agilent Cary 620/670, PerkinElmer Spotlight 400, and Thermo Fischer Scientific Nicolet iN10). Using the same database and the automated analysis pipeline in siMPle, MP were identified in samples that were analyzed with instruments with different detector systems as well as optical resolutions and the results discussed.


Assuntos
Monitoramento Ambiental/métodos , Microplásticos/análise , Software , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise
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