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Objective: To classify the eyelid divided nevi using a new classification method, and to observe the distribution characteristics and surgical effects of these nevi. Methods: It was a retrospective case series study. Thirty-nine cases (39 eyes) of eyelid divided nevus treated at Beijing Tongren Hospital affiliated to Capital Medical University were collected between October 2015 and January 2020. A new classification method, namely traditional classification combined with aesthetic unit classification, was used to classify eyelid divided nevi. According to different classifications, the corresponding surgical treatment methods were adopted. The distribution characteristics of different types of eyelid divided nevi were summarized, as well as the effects of plastic surgery. Results: Thirty-nine patients were affected unilaterally, including 26 females (67%) and 13 males (33%), aged (31.1±17.8) years. There were 5 cases (13%) of localized, 6 cases (15%) of a moderate range and 2 cases (5%) of a large range medial eyelid divided nevus respectively. There were 6 cases (15%) of localized and 3 cases (8%) of a moderate range central eyelid divided nevus, respectively. There were 4 cases (10%) of localized and 6 cases (15%) of a moderate range lateral eyelid divided nevus, respectively. There were 2 cases (5%) of a moderate range and 5 cases (13%) of a large range total eyelid divided nevus, respectively. Pathological results revealed 20 cases of intradermal nevus (51%), 18 cases of compound nevus (46%) and 1 case of boundary nevus (3%). After 6 months to 2 years of observation, the patients' appearance was satisfactory. The treatment results were excellent in 36 cases (92%) and good in 3 cases (8%). Even though the pigmented nevus at the eyelid margin recurred in two cases (5%), there was no recurrence after reoperation. Conclusions: Medial and moderate-range eyelid divided nevi are more common, and the traditional classification combined with aesthetic unit classification is more accurate for the classification of eyelid divided nevi. Different types of eyelid divided nevi can be treated by corresponding surgical methods with satisfactory results.
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Neoplasias de los Párpados , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Cirugía Plástica , Neoplasias de los Párpados/patología , Neoplasias de los Párpados/cirugía , Párpados/cirugía , Femenino , Humanos , Masculino , Nevo/patología , Nevo/cirugía , Nevo Pigmentado/patología , Nevo Pigmentado/cirugía , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
Objective: To discuss the ultrasonic manifestations of blind microphthalmia, and to explore the correlation between axis length and complicity of intraocular structure of blind microphthalmia. Methods: Retrospective case series study. The data of ultrasonic imaging and axis length of 162 patients (162 eyes) with blind microphthalmia diagnosed in Tongren Eye Center, Beijing Tongren Hospital from July 2013 to July 2018 were collected. According to the degree of internal structure disorder, all affected eyes were divided into groups of the normal, the abnormal and the indistinguishable. The binocular axial length in these patients were compared. The relationship between the axial length and the age of the patients, and the structural changes of the blind microphthalmia with a basic structure were analyzed. Statistical methods were mainly performed by paired t-test, one-way linear regression analysis and one-way analysis of variance. Results: The disease was unilateral in all the 162 patients. The age ranged from 1 month to 58 years old. And 139 cases (85.80%) were under 12 years old. There were 90 males and 72 females. The mean axial length of the affected eyes (162 eyes) was (13.17±3.77) mm, while the mean axial length of the control eyes (162 eyes) was (21.85±2.01) mm. There was significantly statistical difference in the ocular size between them (t=-27.369; P<0.01). There was no significant correlation between the axial length of the affected eye and age in patients with unilateral blind microphthalmia (r=0.027; P>0.05), while there was a significant correlation between the axial length of the control eye and age (r=0.590; P<0.01). The axial length of the groups of the normal (14 eyes), the abnormal (91 eyes) and the indistinguishable (57 eyes) was (17.80±2.19) mm, (14.81±2.92) mm and (10.05±2.46) mm, respectively, and the difference was statistically significant (F=72.800; P<0.01), and there was also significant difference between the two groups (all P<0.01). Ocular ultrasonic imaging showed that 105 eyes (64.81%) had a basic ocular structure, 83 eyes (51.23%) had retinal detachment, 15 eyes (9.26%) had bulbar ossification, and 10 eyes (6.17%) had optic disc abnormality. Conclusions: Blind microphthalmia mostly has a basic ocular structure and is often associated with retinal detachment. The axial length of the affected eye is correlated with the degree of intraocular structural disorder. (Chin J Ophthalmol, 2021, 57: 825-829).
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Microftalmía , Niño , Ojo , Femenino , Humanos , Lactante , Masculino , Microftalmía/diagnóstico por imagen , Estudios Retrospectivos , Ultrasonido , UltrasonografíaRESUMEN
Objective: To report the clinical and pathological features and surgical treatment of the linear nevus sebaceous syndrome. Methods: It was a retrospective case series study. The clinical records of 11 patients (14 eyes) who were diagnosed as linear nevus sebaceous syndrome between April 2009 and February 2018 at Beijing Tongren Hospital were analyzed. Data collected included sex, age, clinical manifestations, disease site, pathological features, surgical treatment and therapeutic effects. Results: There were six males and five females, aged 6 months to 7 years (mean, 2.8 years). The nevus sebaceous was located at the head (9 patients), face (5 patients) and neck (3 patients). The most common ocular manifestations were blepharocoloboma (13 eyes) and external ocular mass (9 eyes). Surgical treatment was performed in 9 patients (11 eyes), including lid reconstruction in all these eyes, corneal and conjunctival mass resection in four patients (4 eyes), eyelid tumor resection in 5 patients (5 eyes), and symblepharon separation and conjunctival sac reconstruction in 3 patients (5 eyes). Pathological examinations of the external ocular, corneal and conjunctival masses (6 eyes) confirmed the diagnosis of complex choristoma. All operated patients had improved appearance. Conclusions: Linear nevus sebaceous syndrome has characteristic cutaneous lesions and ocular manifestations. Histopathologically, all epibulbar lesions prove to be complex choristomas. The appearance of patients with linear nevus sebaceous syndrome can be significantly improved by oculoplastic surgery. (Chin J Ophthalmol, 2020, 56: 846-852).
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Coristoma , Nevo Pigmentado , Neoplasias Cutáneas , Conjuntiva , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: Osteogenic differentiation of bone marrow stromal stem cells (BMSCs) is beneficial to the treatment of osteoarthritis (OA). Lnc-RNA BLACAT1 involves in occurrence and development of various diseases. However, the role of Lnc-RNA BLACAT1 in BMSCs differentiation under inflammation remains unclear. MATERIALS AND METHODS: Rat BMSCs were isolated and randomly divided into control group and inflammation group (addition of IL-6). The inflammation group was further divided into BLACAT1 siRNA group and BLACAT1 siRNA+miR-142-5p inhibitor group, followed by analysis of Lnc-RNA BLACAT1 expression by real time PCR, BMSCs proliferation, Caspase 3 activity, ALP activity, expression of Runx2, OC and PPARγ2 by real time PCR, and secretion of TNF-α and IL-1ß by enzyme-linked immunosorbent assay (ELISA). The bioinformatics software and the Luciferase reporter system analyze the targeted relationship between BLACAT1 and miR-142-5p. RESULTS: In inflammation group, Lnc-BLACAT1 expression was increased, along with inhibited BMSCs proliferation, increased Caspase 3 activity, decreased ALP activity, and expression of Runx2 and OC, increased PPARγ2 expression and secretion of TNF-α and IL-1ß. The difference was statistically significant compared with control group (p<0.05). MiR-142-5p is the target miRNA of Lnc-RNA BLACAT1. BLACAT1 siRNA down-regulated BLACAT1 expression, promoted cell proliferation, inhibited Caspase 3 activity, increased ALP activity and Runx2 and OC expression, decreased PPARγ2 expression and TNF-α and IL-1ß secretion. Compared with inflammation group, the difference was statistically significant (p<0.05). Of note, BLACAT1 siRNA+miR-142-5p inhibitor group reversed the effect of siRNA-mediated knockdown of BLACAT1. CONCLUSIONS: Lnc-RNA BLACAT1 expression was increased in inflammatory BMSCs, and knockdown of BLACAT1 promoted proliferation and osteogenic differentiation of BMSCs targeting miR-142-5p.
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Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Osteoartritis/genética , ARN Largo no Codificante/genética , Animales , Células Cultivadas , Femenino , Células Madre Mesenquimatosas/citología , Osteoartritis/metabolismo , Osteoartritis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Objective: To report the clinical features and surgical treatment of orbitotemporal neurofibromatosis. Methods: It was a retrospective case series study. The clinical records of 24 patients who were treated for orbitotemporal neurofibromatosis between April 2007 and July 2017 at Beijing Tongren Hospital, Capital Medical University were analyzed. Data collected included sex, age, laterality, periorbital deformities, surgical treatment, follow-up time, complication and recurrence. Results: Sixteen males and 8 females were included. Age at surgery was (15±7) years (4-30 years). All patients were unilaterally involved. Twenty-three patients (96%) had upper lid involvement and ptosis. Nine patients (38%) had lower lid involvement. Fourteen patients (58%) had lateral canthal disinsertion. Three patients (13%) had brow involvement, 10 patients (42%) had conjunctival involvement and 2 patients (8%) had lacrimal gland infiltration. All patients had tumor debulking procedure. Twenty-two patients (92%) had correction of ptosis. Fourteen patients (58%) required lid reconstruction and lateral canthus reattachment surgery. Three patients (13%) had correction of brow ptosis.One patient (4%) had skull and orbit reconstruction. The median follow-up time was 3.5 (1.0-10.0) years. All patients had improved appearance. Ptosis recurred in 6 patients, but were corrected with surgery. On the last follow-up, 7 patients were free of ptosis. In 14 patients, mild ptosis was noted, but the upper lid did not cover the pupil. In 2 patients the pupil was half covered. Only in 1 patient who had not received ptosis correction surgery the pupil was covered completely. Conclusions: The periorbital deformities of orbitotemporal neurofibromatosis include upper eyelid infiltration with ptosis, lateral canthal disinsertion and infiltration of lower eyelid, brow, conjunctiva and lacrimal gland. The appearance of patients with orbitotemporal neurofibromatosis can be significantly improved through oculoplastic surgery. (Chin J Ophthalmol, 2019, 55: 828-833).
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Neurofibromatosis/diagnóstico , Neurofibromatosis/cirugía , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/cirugía , Adolescente , Adulto , Blefaroplastia , Blefaroptosis/cirugía , Niño , Preescolar , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective: To assess the effectiveness of osseointegrated implant supported prostheses in the rehabilitation of severe orbital deformity. Methods: Retrospective case series. The study collected 6 patients (6 eyes) with severe orbital deformity, who were treated with osseointegrated implant supported prostheses between 2010 and 2016 in Beijing Tongren Eye Center, Beijing Tongren Hospital. Data included demographic characteristics, causes of the deformity, the history of radiotherapy, the site, number and survival of implants, and the ability to wear prostheses. Results: Among the 6 patients, 4 were males, and 2 were females, with a mean age of 27 (16-44) years. The deformity resulted from evisceration or enucleation and radiotherapy for malignancies in 4 patients, from evisceration because of inflammatory pseudotumor in 1 patient, and from enucleation and debridement because of explosion injury and secondary infection in 1 patient. Each patient received 3 implants at the first operation. A total of 18 implants were installed, including 9 placed into the lateral aspect of the supraorbital rim, 6 into the lateral aspect of the infraorbital rim, 1 into the medial aspect of the supraorbital rim, and 2 into the medial aspect of the infraorbital rim. One superior lateral implant failed half a year after implantation, and an additional implant was implanted into the medial aspect of the inferior medial orbital rim for prostheses retention. All the patients were followed up for more than 2 years. No other failures were observed. The soft tissue reaction was acceptable in all patients. All of them were able to wear prostheses with satisfying appearance. Conclusions: Osseointegrated implants provid excellent retention for orbital prostheses. This technique could be used in patients with severe orbital deformity to improve their life quality. (Chin J Ophthalmol, 2019, 55: 665-669).
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Prótesis Anclada al Hueso , Implantes Orbitales , Oseointegración , Implantación de Prótesis , Adolescente , Adulto , Femenino , Humanos , Masculino , Prótesis e Implantes , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective: To evaluate the outcome of autogenic facia lata suspension in the treatment of paralytic ectropion. Methods: It was a retrospective case series study. The clinical records of 21 patients (21 eyes) who were treated for paralytic ectropion with autogenic facia lata suspension between January 2015 and September 2017 at Beijing Tongren Hospital were analyzed. In the 21 patients, 7 were male and 14 were female. The range of age was 20-74 years and the mean age was (61±14) years. All of the participants received facia lata suspension for the correction of ectropion. Some of the patients also received associated wedge resection of the tarsus or lateral tarsal strip procedure. The anterior lamella was reconstructed with local flaps in some patients. The preoperative and postoperative degree of ectropion was measured. Paired sample t test was used to compare the preoperative and postoperative data. Results: Postoperative follow up for patient was conducted for 6-38 months. Residual lagophthalmos of 3 mm or more were present in 3 cases. Mild lower eyelid ectropion recurred in 1 patient one year after surgery. The rest cases achieved satisfactory aesthetic outcomes. No complication in the donor site was observed. The preoperative scleral show was (3.02±1.31) mm, and the postoperative data was (-0.05±0.72) mm. The preoperative margin reflex distance 2(MRD2) was (8.83±1.77) mm, and the postoperative MRD2 was (5.43±0.78) mm. The preoperative lagophthalmos was (6.17±1.91) mm, and the postoperative data was (1.98±1.09) mm. The differences between the preoperative and postoperative data were significant (t=13.530, P=0.000;t=11.913, P=0.000; t=11.882, P=0.000). Conclusion: Autogenic facia lata suspension is an effective method for the correction of paralytic ectropion, with good aesthetic outcome, low recurrence rate and few complications. (Chin J Ophthalmol, 2018, 54: 496-501).
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Ectropión , Párpados , Anciano , Ectropión/cirugía , Párpados/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Colgajos QuirúrgicosRESUMEN
Objective: To observe computed tomography (CT) imaging parameters of congenitally blind microphthalmia in Chinese patients and to provide clinical reference data for the Chinese population. Methods: It was a retrospective study for a consecutive case series of congenitally blind microphthalmia from July 2011 to July 2013. All of the patients were diagnosed in the Ocular Plastic Department, Tongren Eye Center, Beijing Tongren Hospital. We employed multi-section helical CT imaging with a computer-aided design system to observe and measure the imaging features in 82 Chinese patients (85 eyes). The paired T-test was applied for comparing the axial lengths, transverse diameters, and vertical diameters between the both sides in patients with congenital microphthalmia. The Pearson correlation was used for analyzing the relationship between the axial length and the age of the patients. Results: In the 82 patients, the age ranged from 1 month to 40 years old. Forty-one patients were male and 41 were female. The disease was unilateral in 96.34% of the patients. The orbital cysts were observed in 12.94% of them, and 76.47% of them presented basic structures on the CT scan. The abnormalities of the lens (62.35% of the eyes) and vitreous (82.35% of the eyes) were observed. The mean maximum axial length of the affected eyes (85 eyes) was (14.52±0.56) mm and the mean axial length of the unaffected eyes (79 eyes) was (22.79±0.36) mm. There was significantly statistical difference in the ocular size between the affected and unaffected eyes (t= 1.156, P<0.001) . Conclusions: Congenitally blind microphthalmia is usually complicated with the abnormalities of the lens and vitreous. The ocular size decreases significantly. The results of the present study provide a clinical reference for evaluating congenitally blind microphthalmia.(Chin J Ophthalmol, 2018, 54: 199-204).
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Microftalmía , Tomografía Computarizada Espiral , Preescolar , Femenino , Humanos , Lactante , Masculino , Microftalmía/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24- fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.
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Neoplasias de la Mama/patología , MicroARNs/genética , Células Madre Neoplásicas/patología , Proteínas Proto-Oncogénicas c-myc/genética , ARN Mensajero/genética , Proteína Sequestosoma-1/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ratones , Persona de Mediana Edad , Trasplante de Neoplasias , Células Madre Neoplásicas/metabolismo , Pronóstico , Estabilidad del ARN , ARN Mensajero/química , Proteína Sequestosoma-1/genética , Regulación hacia ArribaRESUMEN
BACKGROUND AND PURPOSE: Previous studies of geometric and morphologic parameters of intracranial aneurysms have been conducted to determine rupture risk, which remains incompletely defined due to patient-specific risk factors, such as sex, hypertension, and age. To this end, we compared characteristics of ruptured and unruptured aneurysms in the same patients with symmetric bilateral intracranial aneurysms. MATERIALS AND METHODS: Between January 2008 and March 2014, 2361 patients with 2674 aneurysms were diagnosed by CT angiography or surgical findings at 4 medical centers. Geometric and morphologic parameters examined for symmetric bilateral intracranial aneurysms comprised aneurysm wall regularity, size, neck width, aspect ratio, size ratio, neck-to-parent artery ratio, and area ratio. Univariate and multivariate statistical analyses were performed to determine independent risk factors for rupture. RESULTS: Sixty-three patients (48 women, 15 men; mean age, 62.5 ± 9.8 years) with symmetric bilateral aneurysms were eligible for the study and were included. The most frequent aneurysm location was the posterior communicating artery. Univariate analysis disclosed that aneurysm size, aspect ratio, size ratio, area ratio, and irregular wall differed between patients with ruptured and unruptured aneurysms. Multivariate analysis indicated that aspect ratio of ≥1.6 (adjusted OR, 9.521; 95% CI, 2.182-41.535), area ratio of ≥1.5 (adjusted OR, 4.089; 95% CI, 1.247-13.406), and irregular shape (adjusted OR, 10.443; 95% CI 3.394-32.135) were significant predictive factors for aneurysm rupture after adjustment for aneurysm size. CONCLUSIONS: An aspect ratio of ≥1.6, area ratio of ≥1.5, and irregular wall are associated with aneurysm rupture independent of aneurysm size and patient characteristics. These characteristics alone can help in distinguishing ruptured bilateral intracranial aneurysms from unruptured ones.
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Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/patología , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: One purpose of this study was to examine the feasibility of conducting epidemiological survey on suicidal thoughts and behaviors (hereafter "suicidal thoughts/behaviors"; i.e., any suicidal ideation, serious ideation, planning, and attempts) among older adults in rural China. Another purpose was to investigate among older people in rural China the prevalence of suicidal thoughts/behaviors, as well as their sociodemographic and clinical correlates. METHODS: A randomly selected sample of 263 subjects, 50 years or older, was recruited in a remote rural area of Southwestern China (Mianyang Region, Sichuan Province) and interviewed using structured instruments. Basic sociodemographic and clinical data were collected. RESULTS: There was no refusal among approached subjects, and subjects were willing to answer questions on suicidal thoughts/behaviors. The lifetime prevalence of suicidal ideation, serious ideation, planning, and attempt was 28.9% (23.4%-34.4%), 19.7% (14.9%-24.6%), 11.4% (7.5%-15.3%), and 5.3% (2.6%-8.1%), respectively. The corresponding 12-month prevalence was 8.8% (5.3%-12.2%), 5.3% (2.6%-8.1%), 2.7% (0.7%-4.6%), and 0%, respectively. The 2-week prevalence was 3.4% (1.2%-5.6%), 2.3% (0.5%-4.1%), 2.3% (0.5%-4.1%), and 0%, respectively. Correlates of suicidal thoughts/behaviors of this group are similar to findings from other community studies, such as female gender, unmarried status, major medical conditions, insomnia, financial difficulties and lower education, depressive symptoms, recent stressful life events, greater life dissatisfaction. CONCLUSIONS: Our findings suggest that larger scale epidemiological survey of suicidal thoughts/behaviors on older adults in rural China would be feasible. Suicidal thoughts/behaviors are common among older people in rural China, as seen in this preliminary study, which points to the need for further larger scale investigations.
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Ideación Suicida , Intento de Suicidio/estadística & datos numéricos , Anciano , China/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Población Rural , Intento de Suicidio/psicologíaRESUMEN
BACKGROUND: The distinctive epidemiologic profile of suicide in China, with notably high rates among rural young adult females, invites examination of possible underlying risk factors. Although there are accumulating data regarding the epidemiology of suicide among youth and young adults in China, there are meager data on suicidal ideation and attempts despite its importance. METHODS: Our study in 2005-06 sought to identify all potentially suitable rural participants, aged 16-34 years, from 10 representative villages in rural Sichuan Province. We conducted structured interviews regarding a range of socio-demographic characteristics and suicidal morbidity. RESULTS: 1654 of a potential 3008 participants participated; lifetime and one-year prevalence were: suicidal ideation (18.8% and 5.2%), serious ideation (8.6% and 2.3%), planning (5.8% and 1.5%), and attempt (2.7% and 0.5%). Comparisons among strata of socio-demographic characteristics showed more prevalent suicidal ideation associated with: female gender, lower education, poorer financial perception, greater rurality of residence, and marital status of "never married" or "others". Suicidal attempt was associated with: female gender and a marital status of "others". LIMITATIONS: The study was carried out in one province and caution is required when considering other rural regions of China. There were a substantial number of unapproachable subjects because of their migrant work at distant sites. CONCLUSIONS: Our results revealed an apparently higher prevalence for suicide ideation and planning compared with residents of other countries, but a lower prevalence for attempts. These data suggests that the relatively high rate of suicide in rural China reflects an elevated case fatality ratio due to chosen methods. The results also revealed unique patterns for correlates with the occurrence of ideation and attempts.
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Ideación Suicida , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , China/epidemiología , Femenino , Humanos , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Factores Sexuales , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
ATP7B, the Wilson disease-associated Cu(I)-transporter, and ZntA from Escherichia coli are soft metal P1-type ATPases with mutually exclusive metal ion substrates. P1-type ATPases have a distinctive amino-terminal domain containing the conserved metal-binding motif GXXCXXC. ZntA has one copy of this motif while ATP7B has six copies. The effect of interchanging the amino-terminal domains of ATP7B and ZntA was investigated. Chimeric proteins were constructed in which either the entire amino-terminal domain of ATP7B or only its sixth metal-binding motif replaced the amino-terminal domain of ZntA. Both chimeras conferred resistance to lead, zinc, and cadmium salts but not to copper salts. The purified chimeras displayed activity with lead, cadmium, zinc, and mercury, which are substrates of ZntA. There was no activity with copper or silver, which are substrates of ATP7B. The chimeras were 2-3-fold less active than ZntA. Thus, the amino-terminal domain of P1-type ATPases cannot alter the metal specificity determined by the transmembrane segment. Also, these results suggest that this domain interacts with the rest of the transporter in a metal ion-specific manner; the amino-terminal domain of ATP7B cannot replace that of ZntA in restoring full catalytic activity.
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Adenosina Trifosfatasas/metabolismo , Proteínas de Transporte de Catión/metabolismo , Escherichia coli/enzimología , Degeneración Hepatolenticular/enzimología , Proteínas Recombinantes de Fusión/metabolismo , Adenosina Trifosfatasas/genética , Secuencia de Bases , Proteínas de Transporte de Catión/genética , Cobre/farmacología , ATPasas Transportadoras de Cobre , Cartilla de ADN , Plomo/farmacología , Mutagénesis Sitio-Dirigida , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Zinc/metabolismo , Zinc/farmacologíaRESUMEN
AIM: To study 3,6-dimethamidodibenzopyriodonium gluconate (I-93) antagonistic effects on lipid peroxidation in cerebral cortical neuronal cultures and rat brains during focal cerebral ischemia-reperfusion. METHODS: Cerebral cortical neurons were cultured and rat focal cerebral ischemia-reperfusion model was established by reversible middle cerebral artery occlusion (MCAO) without craniectomy. The efflux of lactate dehydrogenase (LDH) from neurons, content of malondialdehyde (MDA) in neurons and brain homogenate, activity of superoxide dismutase (SOD) in brain homogenate, and index of cerebral edema as well as brain morphology were investigated. RESULTS: I-93 10-40 mumol.L-1 concentration-dependently inhibited efflux of LDH and elevated levels of MDA induced by addition of H2O2(10 mumol.L-1) in vitro. I-93 0.5 mg.kg-1 improved the cerebral morphology, reduced brain edema, decreased MDA content, and enhanced SOD activity in brain homogenate. CONCLUSION: I-93 protects neurons from H2O2-induced neurotoxicity and ischemia-reperfusion mediated damage by increasing the activity of antioxidant enzymes and suppressing the generation of lipid peroxides.
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Antioxidantes/farmacología , Gluconatos/farmacología , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/metabolismo , Animales , Encéfalo/metabolismo , Edema Encefálico/etiología , Isquemia Encefálica/etiología , Células Cultivadas , Corteza Cerebral/citología , Femenino , Infarto de la Arteria Cerebral Media/complicaciones , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/etiología , Superóxido Dismutasa/metabolismoRESUMEN
The incorporations of [3H] thymidine, [3H]uridine and [3H]leucine into DNA, RNA and protein synthesis in leukemia 7712 cells were inhibited by the complex of 3,6-di-(dimethylamino)-dibenzopyriodonium with praseodymium (Pr, rare earth element) dicitrite 34 micrograms/ml for 3-24 h. The degree of inhibition increased in proportion to the incubation time. After being treated with [C17H20N2I]3[Pr(C6H5O7)2] 34 micrograms/ml for 3, 6, 12 and 24 h, the incorporation of [32P]Na2HPO4 into the nucleoprotein of leukemia 7712 cells was inhibited by 49, 57, 65 and 85%, while those into ATP were inhibited by 43, 59, 65 and 83%, respectively. The ID50 of [C17H20N2I]3[Pr(C6H5O7)2] on DNA synthesis in leukemia 7712 cells at 24 h was 22 micrograms/ml. After the complex was removed from the medium entirely, the rate of DNA synthesis decreased with time over 3-12 h. This result indicated that the inhibition mechanism was likely due to damage to the DNA template.