Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Environ Res ; 245: 117995, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38145731

RESUMO

BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.


Assuntos
Proteínas de Escherichia coli , Quinolonas , Escherichia coli , China/epidemiologia , Farmacorresistência Bacteriana , Antibacterianos/farmacologia
2.
Pharmaceutics ; 14(12)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36559231

RESUMO

Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.

3.
Front Aging Neurosci ; 14: 965943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262888

RESUMO

Palmitoylation is a dynamic process that regulates the activity of the modified proteins. Retinal pigment epithelial (RPE) cells play pivotal roles in the visual cycle and maintaining healthy photoreceptor cells. Dysfunctional RPE cells are often associated with degenerative retinal diseases. The aim of the study was to identify potentially palmitoylated proteins in human RPE cells. By using the detergent-resistant membrane, we found 312 potentially palmitoylated peptides which corresponded to 192 proteins in RPE cells, including 55 new candidate proteins which were not reported before. Gene enrichment analysis highlighted significant enrichment of palmitoylated proteins in cell-matrix adhesion, cell-cell recognition, protein cellular localization, and translation, among others. We further studied the effect of 3 potential palmitoylation sites (Cys 799, 900, and 816) of Niemann-Pick type C1 protein (NPC1) on cholesterol accumulation. We found that mutation of any single Cys alone had no significant effect on intracellular cholesterol accumulation while simultaneous mutation of Cys799 and 800 caused significant cholesterol accumulation in the late endosome. No further cholesterol accumulation was observed by adding another mutation at Cys 816. However, the mutation did not alter the cellular localization of the protein. Conclusion: PRE cells have an abundant number of palmitoylated proteins which are involved in cellular processes critical to visual function. The palmitoylation at Cys799 and 800 was needed for cholesterol export, but not the intracellular localization of NPC1.

4.
Int J Ophthalmol ; 15(9): 1437-1443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124179

RESUMO

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

5.
Antibiotics (Basel) ; 10(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34943754

RESUMO

Voriconazole is a triazole antifungal agent commonly used for the treatment and prevention of invasive aspergillosis (IA). However, the study of voriconazole's use in children is limited. The present study was performed to explore maintenance dose to optimize voriconazole dosage in children and the factors affecting voriconazole trough concentration. This is a non-interventional retrospective clinical study conducted from 1 January 2016 to 31 December 2020. The study finally included 94 children with 145 voriconazole trough concentrations. The probability of achieving a targeted concentration of 1.0-5.5 µg/mL with empiric dosing increased from 43 (45.3%) to 78 (53.8%) after the TDM-guided adjustment. To achieve targeted concentration, the overall target maintenance dose for the age group of less than 2, 2 to 6, 6 to 12, and 12 to 18 years old was approximately 5.71, 6.67, 5.08 and 3.31 mg·kg-1/12 h, respectively (p < 0.001). Final multivariate analysis found that weight (p = 0.019), dose before sampling (p < 0.001), direct bilirubin (p < 0.001), urea nitrogen (p = 0.038) and phenotypes of CYP2C19 were influencing factors of voriconazole trough concentration. These factors can explain 36.2% of the variability in voriconazole trough concentration. Conclusion: In pediatric patients, voriconazole maintenance doses under the target concentration tend to be lower than the drug label recommended, but this still needs to be further studied. Age, body weight, dose, direct bilirubin, urea nitrogen and phenotypes of CYP2C19 were found to be influencing factors of voriconazole concentration in Chinese children. The influence of these factors should be taken into consideration during voriconazole use.

6.
Mol Vis ; 27: 632-642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34924743

RESUMO

Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal vascular disease genetically heterogeneous with multiple causative genes. The aim of this study is to report five novel copy number variation (CNV) regions in FEVR patients and to investigate the possible contributions of novel CNVs to FEVR. Methods: In this study, 824 FEVR families were collected. All cases were performed using the targeted next generation sequencing (NGS) assay, and families with no definite pathogenic mutations in FEVR genes were screened for CNVs according to the NGS results. Droplet digital polymerase chain reaction (ddPCR) testing was introduced to validate the screened CNV regions. We also reviewed the clinical presentations of the probands and affected family members associated with the novel CNVs and conducted segregation analysis. Results: Five CNVs in five patients were detected in this study: heterozygous deletions of kinesin family member 11 (KIF11) exons 2-4, KIF11 exon 11, KIF11 exons 1-10, tetraspanin-12 (TSPAN12) exons 1-3, and low-density lipoprotein receptor-related protein 5 (LRP5) exons 19-21. Among the five affected families, TSPAN12 exons 1-3 heterozygous deletion and LRP5 exons 19-21 heterozygous deletion originate from the mother and the father of the proband, respectively. No other family members manifested as FEVR except for the probands. The correlation between disease severity and CNV loci seems uncertain. Conclusions: Five novel CNV loci in FEVR patients were uncovered in this study, including one maternally-inherited and one paternally-inherited CNV region. Though there is no evidence of co-segregation between these CNVs and FEVR, our findings suggest novel genetic risk factors for FEVR.


Assuntos
Oftalmopatias Hereditárias , Cinesinas/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Doenças Retinianas , Tetraspaninas , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Oftalmopatias Hereditárias/genética , Vitreorretinopatias Exsudativas Familiares , Humanos , Mutação , Linhagem , Fenótipo , Doenças Retinianas/genética , Tetraspaninas/genética
7.
Oxid Med Cell Longev ; 2021: 6715758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777691

RESUMO

Age-associated decline in retina function is largely responsible for the irreversible vision deterioration in the elderly population. It is also an important risk factor for the development of degenerative and angiogenic diseases. However, the molecular mechanisms involved in the process of aging in the retina remain largely elusive. This study investigated the role of mTORC1 signaling in aging of the retina. We showed that mTORC1 was activated in old-aged retina, particularly in the ganglion cells. The role of mTORC1 activation was further investigated in Chx10-Cre;Tsc1fx/fx mouse (Tsc1-cKO). Activation of mTORC1 was found in bipolar and some of the ganglion and amacrine cells in the adult Tsc1-cKO retina. Bipolar cell hypertrophy and Müller gliosis were observed in Tsc1-cKO since 6 weeks of age. The abnormal endings of bipolar cell dendritic tips at the outer nuclear layer resembled that of the old-aged mice. Microglial cell activation became evident in 6-week-old Tsc1-cKO. At 5 months, the Tsc1-cKO mice exhibited advanced features of old-aged retina, including the expression of p16Ink4a and p21, expression of SA-ß-gal in ganglion cells, decreased photoreceptor cell numbers, decreased electroretinogram responses, increased oxidative stress, microglial cell activation, and increased expression of immune and inflammatory genes. Inhibition of microglial cells by minocycline partially prevented photoreceptor cell loss and restored the electroretinogram responses. Collectively, our study showed that the activation of mTORC1 signaling accelerated aging of the retina by both cell autonomous and nonautonomous mechanisms. Our study also highlighted the role of microglia cells in driving the decline in retina function.


Assuntos
Envelhecimento , Proteínas de Homeodomínio/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Microglia/patologia , Retina/patologia , Degeneração Retiniana/patologia , Fatores de Transcrição/fisiologia , Proteína 1 do Complexo Esclerose Tuberosa/fisiologia , Animais , Modelos Animais de Doenças , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Retina/metabolismo , Degeneração Retiniana/etiologia , Degeneração Retiniana/metabolismo
8.
Int J Ophthalmol ; 13(11): 1713-1719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33215000

RESUMO

AIM: To demonstrate local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for the treatment of partial rhegmatogenous retinal detachment (RRD) with local vitreous traction in patients at high-risk for proliferative vitreoretinopathy (PVR). METHODS: Eleven eyes of 11 patients were retrospectively studied, including 5 retinal dialysis and 6 retinal detachment (RD; 5 eyes with peripheral retinal hole and 1 eye with giant tear). All patients exhibited partial RD and local vitreous traction. Combined local dry vitrectomy without conventional infusion and segmental scleral buckling was performed. Viscoelastic fluid was injected into the vitreous cavity if needed. Demographic information, preoperative and post-operative complications, and outcomes were recorded. RESULTS: The mean age of the patients at presentation was 26.55±13.52y. All 11 patients obtained retinal reattachment after a single surgical intervention. Postoperative visual acuities were improved or remained stable in all patients. None of them developed complications, except for temporary mildly increased intraocular pressure in 3 cases. CONCLUSION: Combined local dry vitrectomy and segmental scleral buckling are effective for patients of RRD with local vitreous traction. The technique avoids many complications associated with regular surgery and was minimally invasive to both the external and internal eye.

9.
Mol Clin Oncol ; 12(1): 15-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814972

RESUMO

The treatment of hepatocellular carcinoma (HCC) is a significant challenge. Although radiofrequency ablation (RFA) has emerged as a popular therapeutic option for patients with resectable HCC, whether it can achieve comparable survival outcomes compared with surgical resection (RES) remains unclear. The aim of the present study was to conduct a meta-analysis to assess the survival outcomes of RFA vs. RES in patients with early resectable HCC tumors. A Medline, Embase, and Cochrane Library search was performed for data published between January 2000 and February 2018. A meta-analysis of the efficacy of RFA compared with RES for HCC was subsequently performed, with particular emphasis on overall survival and disease-free survival (DFS) rates. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. In the present study, a total of 13,147 patients with HCC were included; of which, 6,727 were treated with RFA and 6,420 were treated with RES. The overall survival rates (OR1-year, 0.757, 95% CI, 0.578-0.989; OR3-year, 0.530, 95% CI, 0.401-0.700; OR5-year, 0.566, 95% CI, 0.423-0.758) and the DRS rates (OR1-year, 0.569, 95% CI, 0.456-0.711; OR3-year, 0.418, 95% CI, 0.267-0.653; OR5-year, 0.374, 95% CI, 0.231-0.606) of RES were significantly higher than those of RFA. The results indicate that RES is superior to RFA for promoting the survival of selected patients with resectable HCC. However, future randomized controlled trials are required to investigate the specific relevance of these modalities in the treatment of HCC.

10.
Sci Rep ; 9(1): 13277, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527693

RESUMO

Accurate dosimetry of a specific brain region in rats exposed to an electromagnetic field (EMF) is essential for studies focusing on dose-effect relationship of the region. However, only dosimetry of whole brain or whole body were evaluated in most of previous studies. In this study, a numerical voxel rat model with 10 segmented brain regions was constructed. Then, the effects of frequency, incidence direction, and E-polarization direction of plane wave EMF on brain region averaged specific absorption rate (BRSAR) of rats were investigated. At last, the reliability of using whole-body averaged SAR (WBDSAR) and whole-brain averaged SAR (WBRSAR) as estimations of BRSAR were also evaluated. Our results demonstrated that the BRSAR depended on the frequency, incidence direction, and E-polarization direction of the EMF. Besides, the largest deviation could be up to 13.1 dB between BRSAR and WBDSAR and 9.59 dB between BRSAR and WBRSAR. The results suggested that to establish an accurate dose-effect relationship, the variance of the BRSAR induced by alteration of frequency, incidence direction, and E-polarization direction of EMF should be avoided or carefully evaluated. Furthermore, the use of WBDSAR and WBRSAR as estimations of BRSAR should be restricted to certain conditions such that the deviations are not too large.


Assuntos
Encéfalo/efeitos da radiação , Campos Eletromagnéticos/efeitos adversos , Radiometria/métodos , Animais , Biologia Computacional , Simulação por Computador , Ratos , Tecnologia sem Fio
11.
Invest Ophthalmol Vis Sci ; 59(13): 5368-5381, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452590

RESUMO

Purpose: To identify potentially pathogenic variants (PPVs) in Chinese familial exudative vitreoretinopathy (FEVR) patients in FZD4, LRP5, NDP, TSPAN12, ZNF408, and KIF11 genes. Methods: Blood samples were collected from probands and their parent(s). Genomic DNA was analyzed by next-generation sequencing, and the sequence of selected variants were validated by Sanger sequencing. The potential pathogenicity of a variant was evaluated by in silico analysis and by cosegregation of the variant with disease. Each proband was subjected to comprehensive retinal examinations, and the severity of FEVR was individually graded for each eye. Whenever possible, fundus fluorescein angiography was obtained and analyzed for parent(s) of each proband. Variation in mutation expressivity was analyzed. Results: Three hundred eighty-nine consecutive FEVR patients from 389 families participated in this study. About 74% of the probands were children younger than 7 years old. One hundred one PPVs, 49 variants with unknown significance (VUS), were identified, including 73 novel PPVs and 38 novel VUS. One hundred ten probands carried PPV (28.3%), and 51 probands carried VUS (13.1%). PPVs in FZD4, LRP5, TSPAN12, NDP, ZNF408, and KIF11 were found in 8.48%, 9.00%, 5.91%, 4.63%, 0.77%, and 0.77% of the cohort, respectively. Probands carrying PPVs in NDP and KIF11 had more severe FEVR in general than those carrying PPVs in other genes. Overall, variants in LRP5 and FZD4 showed more significant variation in phenotype than variants in TSPAN12 and NDP genes. Conclusions: Our study expanded the spectrum of PPVs associated with FEVR.


Assuntos
Oftalmopatias Hereditárias/genética , Proteínas do Olho/genética , Variação Genética , Doenças Retinianas/genética , Adolescente , Povo Asiático/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Vitreorretinopatias Exsudativas Familiares , Feminino , Angiofluoresceinografia , Receptores Frizzled/genética , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Cinesinas/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Mutação , Proteínas do Tecido Nervoso/genética , Fenótipo , Reação em Cadeia da Polimerase , Tetraspaninas/genética , Fatores de Transcrição/genética , Adulto Jovem
12.
Int J Ophthalmol ; 11(2): 196-200, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487806

RESUMO

AIM: To reveal age-related aqueous cytokine changes in human aqueous humor. METHODS: Aqueous humor was collected from 12 young children (3-6.5 years old) and 71 healthy adults (22-106 years old) with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor (VEGF) were measured and analyzed. RESULTS: The following proteins showed significant increase from childhood to adult: interferon-gamma (IFN-γ), interleukin (IL)-13, IL-6, IL-12(p70), IL-10, CCL2, CCL3, CCL4, CXCL8, CXCL9, CXCL10, IFN-α2 and VEGF (all P<0.05). IFN-γ, IL-13, IL-12(p70), IL-10, CCL3, CXCL9 and VEGF also showed moderate strength age-related increase in the adult group (r>0.5). The strength of correlation between aging and CCL4 were fair (r=0.398). The concentrations of IL-2, IL-4, IL-5, IL-1ß and TNF-α were low in both groups. CONCLUSION: From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.

13.
Invest Ophthalmol Vis Sci ; 58(3): 1719-1725, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28324112

RESUMO

Purpose: To investigate timing and risk factors of recurrent retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) monotherapy. Methods: Fifty eyes (the more severe eye) of 50 infants treated with IVR monotherapy for type 1 ROP were studied retrospectively. The mean follow-up time was 31 weeks after IVR. Recurrent ROP (recurrence of extraretinal fibrovascular proliferation [EFP]) was determined by RetCam wide-angle fundus imaging and binocular indirect ophthalmoscopy. Risk time of recurrence was estimated by Kaplan-Meier survival analysis with recurrence as the endpoint. Time-varying recurrence hazard rate was determined using the hazard function of life-table analysis. The risk factors of recurrence were explored by logistic regression analysis. Results: Recurrence of ROP occurred in 32 (64%) of 50 eyes at 7.9 ± 2.7 weeks after IVR. Most of recurrence (94%) occurred in 2.5 to 12.0 weeks following IVR treatment. The recurrence hazard rate reached its maximum at 8 weeks. Recurrence affecting the initial site of EFP occurred significantly earlier than recurrence only at the new vascular advancing edge (4.5 ± 1.4 weeks versus 9.1 ± 2.0 weeks after IVR, P < 0.001). The independent risk factors of recurrence included extensive retinal neovascularization (P = 0.005) and oxygen requirement after IVR (P = 0.016). Conclusions: Recurrence of type 1 ROP should be carefully watched in a long-term follow-up after IVR monotherapy, particularly in the first 12 weeks after IVR and for those with extensive retinal neovascularization or prolonged oxygen therapy.


Assuntos
Ranibizumab/administração & dosagem , Retina/patologia , Retinopatia da Prematuridade/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Recém-Nascido , Injeções Intravítreas , Masculino , Oftalmoscopia , Prognóstico , Recidiva , Retinopatia da Prematuridade/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
14.
BMC Mol Biol ; 17(1): 12, 2016 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-27159997

RESUMO

BACKGROUND: Cells respond to DNA damage by activating the phosphatidylinositol-3 kinase-related kinases, p53 and other pathways to promote cell cycle arrest, apoptosis, and/or DNA repair. Here we report that protein palmitoylation, a modification carried out by protein acyltransferases with zinc-finger and Asp-His-His-Cys domains (zDHHC), is required for proper DNA damage responses. RESULTS: Inhibition of protein palmitoylation compromised DNA damage-induced activation of Atm, induction and activation of p53, cell cycle arrest at G2/M phase, and DNA damage foci assembly/disassembly in primary mouse embryonic fibroblasts. Furthermore, knockout of zDHHC16, a palmitoyltransferase gene identified as an interacting protein for c-Abl, a non-receptor tyrosine kinase involved in DNA damage response, reproduced most of the defects in DNA damage responses produced by the inhibition of protein palmitoylation. CONCLUSIONS: Our results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation.


Assuntos
Proteínas de Transporte/metabolismo , Dano ao DNA , Reparo do DNA , Aciltransferases , Animais , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Transporte/genética , Pontos de Checagem do Ciclo Celular , Células Cultivadas , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Deleção de Genes , Técnicas de Inativação de Genes , Lipoilação , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteína Supressora de Tumor p53/metabolismo
15.
Sci Rep ; 6: 26564, 2016 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-27212378

RESUMO

KIF11 gene mutations cause a rare autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR). Recently, such mutations were also found to be associated with familial exudative vitreoretinopathy (FEVR). Here, we report 7 novel KIF11 mutations identified by targeted gene capture in a cohort of 142 probands with FEVR who were diagnosed in our clinic between March 2015 and November 2015. These mutations were: p.L171V, c.790-2A>C, p.Q525*, p.Q842*, p.S936*, p.L983fs and p.R1025G. Phenotypic analysis revealed that all of the affected probands had advanced FEVR (stage 4 or above). Three had microcephaly, and one had chorioretinopathy, which indicated a phenotypic overlap with MCLMR. Two mutations were also found in the families of the affected probands. One parent with a p.R1025G mutation had an avascular peripheral retina and abnormal looping vessels. However, one parent with p.L983fs had normal retina, which indicated incomplete penetration of the genotype. Our results further confirmed that KIF11 is causative of FEVR in an autosomal dominant manner. We also suggest the examination of MCLMR-like features, such as microcephaly, chorioretinopathy, for patients with FEVR and wide-field fundus photography for patients with MCLMR in future practice.


Assuntos
Cinesinas/genética , Mutação , Doenças Retinianas/genética , Doenças Retinianas/patologia , Criança , Pré-Escolar , Oftalmopatias Hereditárias , Vitreorretinopatias Exsudativas Familiares , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Análise de Sequência de DNA
16.
Acta Ophthalmol ; 94(4): 365-72, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26855122

RESUMO

PURPOSE: Four-port bimanual vitrectomy is a surgical technique that facilitates removal of epiretinal membranes in severe proliferative diabetic retinopathy (PDR). As the illumination is held by the assistant through the fourth scleral incision, fibrovascular membranes are removed by bimanual manipulation techniques. The objective of this study was to evaluate the safety and efficacy of four-port bimanual 23-gauge vitrectomy for patients with tractional retinal detachment (TRD) in severe PDR. DESIGN: Retrospective, comparative, consecutive, interventional case series. METHODS: Sixty-six eyes of 58 consecutive patients who underwent primary vitrectomy for severe diabetic TRD. Thirty-six eyes of 31 cases that were treated with four-port 23-gauge vitrectomy were compared with 30 eyes of 27 cases that were treated with 23-gauge pars plana vitrectomy (PPV). Main outcome measures were best-corrected visual acuity (BCVA), retinal status, intraocular pressure, and incidence of intraoperative and postoperative complications with at least 6 months of follow-up. RESULTS: The primary and ultimate anatomic success rates (94.4% versus 93.3%, and 100% in both groups, respectively) and the mean BCVA changes did not differ significantly between groups. The whole surgical time and the membrane removal time were significantly (p < 0.001, respectively) shorter in the four-port 23-gauge group than in the 23-gauge group. There was no difference in the incidence of intraoperative and postoperative complications in both groups. CONCLUSIONS: Four-port bimanual 23-gauge vitrectomy offers comparable anatomic success and shortens the surgical time compared with conventional 23-gauge PPV in patients with TRD resulting from severe PDR.


Assuntos
Retinopatia Diabética/cirurgia , Descolamento Retiniano/cirurgia , Vitrectomia/métodos , Adulto , Idoso , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Pressão Intraocular/fisiologia , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Descolamento Retiniano/etiologia , Descolamento Retiniano/fisiopatologia , Estudos Retrospectivos , Acuidade Visual/fisiologia
18.
Zhonghua Yan Ke Za Zhi ; 47(6): 564-7, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21914273

RESUMO

Retinopathy of prematurity (ROP) is a proliferative disease that affects prematurely born babies. Despite the progress in management and treatment obtained previously, ROP remains a major cause of childhood blindness in both developed and developing countries. The etiology and pathogenesis of ROP is still unclear despite the fact that some progresses have been obtained. Some factors, such as low birth-weight and short gestational age have been consistently shown to be associated with ROP. Recently, numerous studies indicated that ROP shows genetic susceptibility, which includes sex, ethnicity, gene polymorphisms and gene mutations. Genetic susceptibility will play an important role in the screening and treatment of advanced ROP in the future.


Assuntos
Predisposição Genética para Doença , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/genética , Humanos , Recém-Nascido
19.
AJR Am J Roentgenol ; 190(1): 105-10, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18094300

RESUMO

OBJECTIVE: The objective of our study was to evaluate the feasibility and effectiveness of percutaneous chemical ablation of primary and metastatic adrenal neoplasms under CT guidance. MATERIALS AND METHODS: Thirty-seven patients with 46 adrenal tumors underwent CT-guided percutaneous chemical ablation. The average (+/- SD) tumor diameter was 4.2 +/- 2.0 cm. Acetic acid was injected in lesions with a diameter of more than 3 cm, and ethanol was injected in lesions with a diameter of less than 3 cm. Eleven adrenal lesions were nonfunctional adenomas, six lesions were corticosteroid adenomas (bilateral lesions in one patient), nine lesions were aldosteronomas (bilateral lesions in two patients), and 20 were metastases (bilateral metastases in six patients). RESULTS: Tumor volume decreased gradually during the first 2 years after the procedure. For primary tumors, a complete response (CR) rate of 92.3% (24/26) and a partial response (PR) rate of 7.7% (2/26) were obtained, but for metastasis, a CR rate of 30% (6/20) and PR rate of 70% (14/20) were obtained 24 months after therapy. The level of corticosteroid in five patients (six tumors) with Cushing's syndrome was in the normal range 3 months after the procedure. Seven patients (nine tumors) with Conn's syndrome began receiving oral antihypertensive medications during the first month after the procedure to maintain normal blood pressure and the dose was gradually decreased after 1 month. No severe complications were encountered. CONCLUSION: CT-guided percutaneous chemical ablation of adrenal tumors is an effective, minimally invasive, and easily performed procedure.


Assuntos
Ácido Acético/administração & dosagem , Adenoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Carcinoma/tratamento farmacológico , Etanol/administração & dosagem , Segunda Neoplasia Primária/tratamento farmacológico , Adenoma/diagnóstico por imagem , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Idoso , Biópsia por Agulha , Carcinoma/secundário , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...