RESUMO
OBJECTIVE: To determine the advantages and complication rate of capsulotomy performed with femtosecond laser in white complex cataract cases. STUDY DESIGN: Retrospective case series. PARTICIPANTS: Sixteen eyes of 16 patients. METHODS: This was a single-center retrospective review of white cataract surgery cases in which the femtosecond laser (LenSx, Alcon Laboratories, Fortworth, Texas, USA) was used between May 2019 and February 2021. Outcome measures included an assessment of the capsulotomy, identification of tags, surgical time, cumulative dispersed energy (CDE) and postoperative management. RESULTS: Sixteen eyes of 16 patients were included in this study; capsule tags occurred in six patients (37.5%). In 2 patients, the capsule presented small adhesions that were identified and removed. One patient presented a very significant contraction of the anterior capsule with an incomplete cut zone of 2 to 4hours. In a patient with nystagmus, the capsulotomy was performed without complications under peribulbar anesthesia. CONCLUSIONS: The femtosecond laser permitted capsulotomies of better shape, size and regularity in complex cases of white cataract and in combination with conditions such as nystagmus and prior corneal transplantation. The microadhesions and untreated areas were identified with trypan blue, which is essential to use in these cases to avoid associated complications.
Assuntos
Extração de Catarata , Catarata , Terapia a Laser , Facoemulsificação , Humanos , Estudos Retrospectivos , Terapia a Laser/efeitos adversos , Extração de Catarata/efeitos adversos , Catarata/complicações , LasersRESUMO
This study presents the analysis of the natural long-term aging of both the intact tablets and the active pharmaceutical ingredient. No forced aging conditions were applied to the samples. It is shown that the near infrared spectroscopy of the intact tablets packed in plastic blisters, supported by chemometrics, is a reliable method for detection of even slight deviations of the medicine from its regular state. Independent components analysis helps to extract source signals from spectra of the composite object "a coated tablet sealed in polyvinylchloride blister". Further analysis of the near infrared and attenuated total reflectance infrared spectra of the pure substance confirmed that the aging process detected by the analysis of the intact tablets is directly related to the degradation of the active pharmaceutical ingredient.
Assuntos
Análise de Dados , Diclofenaco , Quimiometria , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Comprimidos/químicaRESUMO
BACKGROUND AND PURPOSE: The transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO-1 cis-dimers in the regulation of its biological activity. EXPERIMENTAL APPROACH: LINGO-1 homodimers were identified in both HEK293 and SH-SY5Y cells using co-immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis-driven screen for identification of small-molecule protein-protein interaction modulators of LINGO-1 using a BRET-based assay, adapted for screening. The compound identified was further assessed for effects on LINGO-1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology. KEY RESULTS: LINGO-1 was present as homodimers in primary neuronal cultures. LINGO-1 interacted homotypically in cis-orientation and LINGO-1 cis-dimers were formed early during LINGO-1 biosynthesis. A BRET-based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO-1 dimers. In HEK-293 cells, phenoxybenzamine was a positive modulator of LINGO-1 function, increasing the LINGO-1-mediated inhibition of EGF receptor signalling and Erk phosphorylation. CONCLUSIONS AND IMPLICATIONS: Our data suggest that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery.
Assuntos
Proteínas de Membrana/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Fenoxibenzamina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Dimerização , Células HEK293 , Humanos , Proteínas de Membrana/metabolismo , Estrutura Molecular , Peso Molecular , Proteínas do Tecido Nervoso/metabolismo , Fenoxibenzamina/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
We have performed a phylogenetic analysis of 59 mariner elements in 14 Drosophilidae species that are related to the active Drosophila mauritiana Mos1 element. This includes 38 previously described sequences and 21 new sequences amplified by PCR from 10 species. Most of the elements detected are nonfunctional due to several frameshifts and deletions. They have been subdivided into four groups according to specific signatures in the nucleotidic and amino acid sequences. The mean nucleotide diversity is 4.8 +/- 0.1% and reflects mainly the divergence of inactive elements over different periods. Although this probably gives rise to occasional homoplasies between distantly related taxa, the elements of each species remain grouped together. Horizontal transfer, reported previously between D. mauritiana and Zaprionus tuberculatus, can be extended to Z. verruca, while the Mos1-like element of Z. indianus belongs to another group. Interpretation of the phylogeny leads to a comparison of the influence of common ancestral sequences and putative horizontal transfers.
Assuntos
Elementos de DNA Transponíveis/genética , Drosophila/genética , Drosophilidae/genética , Evolução Molecular , Filogenia , Animais , Clonagem Molecular , Sequência Consenso/genética , Proteínas de Ligação a DNA , Variação Genética/genética , Mutação/genética , Polimorfismo Genético/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , TransposasesRESUMO
The distribution of the mariner transposable element among Drosophilidae species was investigated using three different techniques, i.e. squash blots, Southern blots and PCR amplification, using two sets of primers (one corresponding to the Inverted Terminal Repeats and the other to two conserved regions of the putative transposase). Our results and those of others show that the distribution of mariner is not uniform and does not follow the phylogeny of the host species. An analysis of geographical distribution, based on endemic species, shows that mariner is mainly present in Asia and Africa. At least two hypotheses may be proposed to explain the specific and geographical distributions of this element. Firstly, they may be the results of several horizontal transmissions between Drosophila species and/or between Drosophila species and one or several donor species outside the Drosophilidae family. Secondly, these particular distributions may correspond to the evolution of the mariner element from an ancestral copy which was present in the ancestor of the Drosophilidae family.
Assuntos
Elementos de DNA Transponíveis , Drosophilidae/genética , Animais , Sequência de Bases , Southern Blotting , Drosophila/genética , Immunoblotting , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Distribuição AleatóriaRESUMO
The mariner transposable elements of several natural populations of Drosophila teissieri, a rainforest species endemic to tropical Africa, were studied. Natural populations trapped along a transect from Zimbabwe to the Ivory Coast were analyzed by Southern blotting, in situ hybridization, cloning, and sequencing of PCR products. The Brazzaville population had some full-length elements, while the remaining populations had mainly deleted elements. The main class of deleted elements lacked a 500-bp segment. A mechanism is proposed that could generate such elements rapidly. In situ hybridizations showed that there are no mariner elements in pericentromeric heterochromatin. Finally, the phylogeny of the Mos1-like mariner full-length elements is consistent with vertical transmission from the ancestor of the melanogaster subgroup.