RESUMO
Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient's baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616-0.729, P < .001), 0.742 (95% CI 0.690-0.794, P < .001), 0.598 (95% CI 0.537-0.659, P = .002), and 0.875 (95% CI 0.839-0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.
Assuntos
Hemorragia Gastrointestinal , Inibidores da Agregação Plaquetária , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Curva ROC , Medição de Risco , Fatores de RiscoRESUMO
Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.
Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Idoso , Anticoagulantes/uso terapêutico , China/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Varfarina/efeitos adversos , Varfarina/uso terapêuticoRESUMO
Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm of low malignant potential that mainly affects infants and adolescents. The tumor almost exclusively occurs in somatic soft tissue or the retroperitoneum. We report herein two cases of primary KHE occurring in a long bone without cutaneous changes with long-term follow up in young patients. The patients were a 9-year-old girl and 5-year-old boy presenting with lytic lesions of the femur and humerus, respectively, without cutaneous lesions. Histologically, the neoplasms were comprised of nodules of spindle- to oval-shaped cells growing in an infiltrative fashion. The neoplastic cells formed poorly canalized or slit-like blood vessels alternating with solid spindle areas. Immunohistochemical studies showed that the tumor cells expressed CD31, CD34 and Fli1, but not HHV8, LNA-1 or GLUT1. D2-40 stained the neoplastic spindle cells and lymphatic channels adjacent to vascular lobules. The girl remains well with 15 years and 6 months follow up after a second complete excision. The boy has no signs of recurrence or metastasis nearly 5 years after local complete excision. To our best knowledge, this is the first report in the English literature of primary long bone occurrences of KHE without cutaneous changes with long-term follow up.
Assuntos
Neoplasias Ósseas/patologia , Hemangioendotelioma/patologia , Úmero , Síndrome de Kasabach-Merritt/patologia , Recidiva Local de Neoplasia/patologia , Sarcoma de Kaposi/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/ultraestrutura , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/patologia , Neoplasias Femorais/cirurgia , Neoplasias Femorais/ultraestrutura , Seguimentos , Hemangioendotelioma/diagnóstico por imagem , Hemangioendotelioma/cirurgia , Hemangioendotelioma/ultraestrutura , Humanos , Úmero/diagnóstico por imagem , Úmero/patologia , Úmero/ultraestrutura , Síndrome de Kasabach-Merritt/diagnóstico por imagem , Síndrome de Kasabach-Merritt/cirurgia , Síndrome de Kasabach-Merritt/ultraestrutura , Masculino , Recidiva Local de Neoplasia/cirurgia , Sarcoma de Kaposi/diagnóstico por imagem , Sarcoma de Kaposi/cirurgia , Sarcoma de Kaposi/ultraestrutura , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: To study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system (CNS-HB). METHODS: Histopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information. RESULTS: Twenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors (endocrine tumor and microcystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB (34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal cells. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin alpha and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices. CONCLUSIONS: VHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB, which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that, regular clinical inspection is recommended in order to check up the development of any new lesions.
Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Hemangioblastoma/patologia , Doença de von Hippel-Lindau/patologia , Adolescente , Adulto , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/cirurgia , Criança , Receptores ErbB/metabolismo , Feminino , Seguimentos , Proteína Glial Fibrilar Ácida/metabolismo , Hemangioblastoma/metabolismo , Hemangioblastoma/cirurgia , Humanos , Inibinas/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Neoplasias da Retina/cirurgia , Análise de Sobrevida , Vimentina/metabolismo , Adulto Jovem , Doença de von Hippel-Lindau/metabolismo , Doença de von Hippel-Lindau/cirurgiaRESUMO
OBJECTIVE: To explore the effect of prostatectomy on nocturia in patients with benign prostatic hyperplasia (BPH). METHODS: The data of patients who had received prostatectomy for BPH between June 2006 and December 2007 were collected. Nocturia severity was assessed preoperatively and 3 to 6 months after prostatectomy by the number of nocturia events, the time from falling sleep to the first awakening to void (hours of undisturbed sleep, HUS), the score of the nocturia quality of life (N-QOL) questionnaire, the International Prostatic Symptom Score (IPSS) and the quality of life (QOL) score. RESULTS: One hundred and twenty five cases were included. Of them, 73 patients finished the follow-up completely. There were 62 patients whose number of nocturia events before the operation was equal or more than 2. The data from these 62 patients were analyzed. Of them, 56 patients underwent transurethral resection of prostate, the remaining 11 patients suprapubic prostatectomy. Significant improvement (P < 0.01) was noted in all the following parameters after treatment: the number of nocturia events decreased from 4.2 ± 2.4 to 2.2 ± 1.0, HUS increased from (1.8 ± 0.7) h to (3.0 ± 1.4) h, N-QOL score raised from 30 ± 10 to 40 ± 7, IPSS decreased from 23 ± 5 to 8 ± 5, and QOL score fell down from 4.4 ± 0.7 to 1.5 ± 1.0. CONCLUSION: The prostatectomy can markedly improve the symptoms of nocturia, sleep and life quality in the BPH patients who accompanied with nocturia.
Assuntos
Noctúria/cirurgia , Prostatectomia , Hiperplasia Prostática/cirurgia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Noctúria/complicações , Hiperplasia Prostática/complicações , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Sistema Justaglomerular/patologia , Neoplasias Renais/patologia , Actinas/metabolismo , Adulto , Antígenos CD34/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Tumor Glômico/metabolismo , Tumor Glômico/patologia , Hemangiopericitoma/metabolismo , Hemangiopericitoma/patologia , Humanos , Hipertensão/etiologia , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/cirurgia , Sistema Justaglomerular/ultraestrutura , Neoplasias Renais/complicações , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Neoplasias Renais/ultraestrutura , Nefrectomia , Tumor de Wilms/metabolismo , Tumor de Wilms/patologiaRESUMO
Recreational and occupational exposure to seawater (SW), have increased but the effect of SW on skin has not been elucidated. The purpose of present study was to assess the effects of SW immersion on the dorsal skin in hairless mice. Adult hairless mice were individually immersed in SW for 3 h, 6 h and 12 h; then, full-thickness dorsal skin of 2 cm diameter was excised for pathological examination (light microscope), apoptosis detection (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling [TUNEL]) and proliferation index evaluation (immunohistochemistry). Normal and normal saline (NS)-immersed skin were used as controls. Histological examination revealed that there were randomly distributed cell deaths, presenting cell shrinkage, condensation of nuclear chromatin and eosinophilic cytoplasm in the epidermis, and neutrophil infiltration in the dermis, after SW immersion. Moreover, TUNEL showed low levels of apoptosis in normal (9.07 +/- 0.70%) and NS-immersed skin (9.99 +/- 1.22%). There was an apparent increase in the 6-h and 12-h SW immersed groups (29.90 +/- 6.85%, P < 0.01; 45.46 +/- 6.12%, P < 0.01, respectively). Ki-67 antigen was located in the basal layer of the epidermis and hair follicles, the rates of Ki-67-positive cells were 7.90 +/- 1.45% and 7.76 +/- 1.52% in normal and NS-immersed skin, respectively, and in the 12-h SW immersed group, the rate of Ki-67-positive cells reached 23.85 +/- 4.21% (threefold, P < 0.01). In each group, the rate of apoptosis was higher than that of proliferation. We conclude that SW immersion can cause time-dependent apoptosis and proliferation in the epidermis, and the overall effect of SW immersion is injury to the epidermis.
Assuntos
Apoptose/fisiologia , Proliferação de Células , Água do Mar/efeitos adversos , Pele/citologia , Animais , Humanos , Imersão/efeitos adversos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/análise , Camundongos , Camundongos PeladosRESUMO
OBJECTIVE: To study the clinicopathologic features and biologic behavior of renal cell carcinoma (RCC) with rhabdoid features. METHODS: Ten cases of RCC with rhabdoid features collected during the period from 1995 to 2005 were enrolled into the study. The clinical findings were analyzed and the hematoxylin and eosin-stained sections were reviewed. Immunohistochemistry and electron microscopy were also performed. RESULTS: The age of patients ranged from 33 to 69 years (mean age = 52 years). Nine of the patients were males and 1 female. Five patients showed evidence of perinephric invasion. Two patients presented with regional lymph node metastases and 1 patient showed distant metastasis to the lung. Histologically, the rhabdoid foci were characterized by loosely cohesive trabeculae, acini, lobules and clusters of rhabdoid cells in otherwise clear cell RCC (9 cases) or papillary RCC (1 case). The rhabdoid cells were round to polygonal in shape and contained globular eosinophilic inclusion bodies in the cytoplasm, eccentric nuclei, vesicular chromatin pattern and prominent nucleoli. Coagulative tumor necrosis was commonly seen. Immunohistochemical study showed that the rhabdoid cells were diffusely positive for CD10 (10/10), cytokeratin AE1/AE3 (10/10), epithelial membrane antigen (10/10) and vimentin (10/10). Focal staining for neuron-specific enolase and S-100 protein was also noted. They were negative for CK7, CK20 and myogenic markers (including myogenin, smooth muscle actin and muscle-specific actin). The mean Ki-67 labeling index of the rhabdoid component was higher than that of the non-rhabdoid component (P < 0.05). Follow-up information was available in 8 patients. While 6 patients are still alive without recurrence, 2 patients died of the disease 6 and 29 months respectively after the operation. CONCLUSIONS: RCC with rhabdoid elements are mainly observed in clear cell RCC and need to be distinguished from oncocytic renal tumors and malignant rhabdoid tumor of kidney. The higher proliferative activity in the rhabdoid areas may indicate more aggressive biologic behavior.
Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Tumor Rabdoide/patologia , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/cirurgia , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucina-1/metabolismo , Nefrectomia , Neprilisina/metabolismo , Tumor Rabdoide/metabolismo , Tumor Rabdoide/cirurgia , Vimentina/metabolismoRESUMO
BACKGROUND: UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. OBJECTIVE: The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. METHODS: Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. RESULTS: The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. CONCLUSION: The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.
Assuntos
Epiderme/metabolismo , Epiderme/efeitos da radiação , Lipídeos , Raios Ultravioleta , Animais , Fenômenos Biofísicos , Biofísica , Epiderme/ultraestrutura , Masculino , Camundongos , Camundongos Pelados , Microscopia Eletrônica , Permeabilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Água/metabolismoRESUMO
UNLABELLED: OBJECTIVE To study the clinicopathologic features, radiologic findings, treatment modalities and prognosis of dysembryoplastic neuroepithelial tumor (DNT). METHODS: The clinical features, histopathologic findings, immunohistochemistry and electron microscopy of 18 cases of DNT were analyzed. Results Among the 18 cases studied, 14 were males and 4 females. The age of these patients ranged from 3 to 46 (mean age = 22. 8 years). Partial seizure was the main presenting symptom in all patients. The history of epilepsy could be as long as 17 years. On magnetic resonance imaging (MRI) study, the tumor was hypodense on T1 and hyperdense on T2. There was neither edema nor mass effect. All but 2 cases were supratentorial and intracortical in location. Ten cases were treated by complete surgical excision and the remaining 8 tumors were partially excised. In the 14 patients with follow-up data available, 13 survived for 1.4 to 11 years after the operation (with more than 10 years survival observed in 2 patients). The average survival period was 5.5 years. None of the cases showed tumor recurrence after operation. Histologically, all tumors demonstrated a multinodular architecture and were intracortical in location, sometimes with extension into the white matter. The characteristic "glioneuronal constituent" was an essential feature for making the diagnosis of DNT. The tumor was formed by an admixture of oligodendrocyte-like cells, mature neurons and astrocytes, with obvious microcystic changes. These neurons were often dispersed singly in the mucoid matrix. In most cases, the foci of cortical dysplasia were found in adjacent areas. Immunohistochemical study demonstrated positivity for synaptophysin, neurofilament and S-100 protein in the neurons and some oligodendrocyte-like cells. The staining of glial fibrillary acidic protein in the oligodendrocyte-like cells was negative. Electron microscopy showed early neuronal, astrocytic and oligodendroglial differentiation of the oligodendrocyte-like cells. CONCLUSIONS: DNT is a benign tumor (corresponding to WHO grade I) that can be cured by surgical excision, despite sometimes incomplete tumor removal. A correct diagnosis of this entity requires thorough understanding of the clinical, radiologic, histologic and immunohistochemical features.
Assuntos
Neoplasias Encefálicas/patologia , Córtex Cerebral/patologia , Neoplasias Neuroepiteliomatosas/patologia , Oligodendroglia/patologia , Adolescente , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Córtex Cerebral/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/metabolismo , Neoplasias Neuroepiteliomatosas/cirurgia , Proteínas de Neurofilamentos/metabolismo , Oligodendroglia/ultraestrutura , Proteínas S100/metabolismo , Taxa de Sobrevida , Sinaptofisina/metabolismoRESUMO
The present study describes a flexible nanoplatform based on electrostatic assembly of conjugated polyelectrolytes (CPEs) and carboxylated multi-walled carbon nanotubes (cMWNTs). It is demonstrated that the obtained nanocomposites inherit intrinsic optical properties of CPEs and characteristic Raman vibration modes of MWNTs, providing a fluorescence-Raman dual-imaging method for intracellular tracking and locating of MWNTs. We suggest that the cellular internalization of the CPE-cMWNT nanocomposites is a surface charge-dependent process. The strengths of this nanoplatform include satisfying biocompatibility, enhanced protein-repellent property, and ease of implementation, making it available for both in vitro and in vivo applications.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Eletrólitos/química , Nanotubos de Carbono/química , Polímeros/química , Análise Espectral Raman/métodos , Adsorção , Animais , Materiais Biocompatíveis , Carbono/química , Linhagem Celular Tumoral , Citocromos c/química , Sistemas de Liberação de Medicamentos , Hemoglobinas/química , Cavalos , Humanos , Microscopia de Fluorescência , Nanocompostos/química , Nanotecnologia , Óptica e Fotônica , Eletricidade EstáticaRESUMO
OBJECTIVE: Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH. METHODS: Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals. RESULTS: Histopathological analysis showed melanocytes in normal control's skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6. CONCLUSION: Our data add new variants to the repertoire of ABCB6 mutations with DUH.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transtornos da Pigmentação/congênito , Dermatopatias Genéticas/genética , Adulto , Povo Asiático , Feminino , Ligação Genética/genética , Predisposição Genética para Doença , Humanos , Técnicas In Vitro , Masculino , Mutação , Linhagem , Transtornos da Pigmentação/genéticaRESUMO
Renal cell carcinomas (RCCs) with t(6;11)(p21;q12) are extremely rare and characterized by specific chromosome translocation, involving the transcription factor EB (TFEB). Fewer than 30 cases have been described in the literature. We examined 7 additional cases of this rare tumor by clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Four tumors had the typical morphologic features of TFEB RCCs, whereas 3 cases demonstrated uncommon morphologic features, mimicking epithelioid angiomyolipoma, chromophobe cell RCC, and clear cell RCC, respectively. Immunohistochemically, aside from TFEB and cathepsin K, kidney-specific cadherin was another sensitive and relatively specific marker for TFEB RCCs, supporting a distal nephron origin for these renal tumors. We also observed different ultrastructures including mitochondrion with areas of lipofuscin pigment in the smaller cells in these cases. An identical Alpha-TFEB fusion gene, 486 bp, was identified in 2 cases. In addition to the polymerase chain reaction method, we also developed a fluorescence in situ hybridization assay to serve as a cost-effective and time-efficient diagnostic tool. We detected a TFEB gene rearrangement in all 7 cases using the fluorescence in situ hybridization method. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none of the cases developed tumor recurrence, progression, or metastasis.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 6/genética , Neoplasias Renais/genética , Translocação Genética , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , DNA de Neoplasias/análise , Feminino , Fusão Gênica , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente/métodos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Nefrectomia , Resultado do Tratamento , Adulto JovemRESUMO
This paper presents a systematic review of the literature concerning fluoride that was carried out to investigate whether fluoride exposure increases the risk of low intelligence quotient (IQ) in China over the past 20 years. MEDLINE, SCI, and CNKI search were organized for all documents published, in English and Chinese, between 1988 and 2008 using the following keywords: fluorosis, fluoride, intelligence, and IQ. Further search was undertaken in the website www.fluorideresearch.org because this is a professional website concerning research on fluoride. Sixteen case-control studies that assessed the development of low IQ in children who had been exposed to fluoride earlier in their life were included in this review. A qualitative review of the studies found a consistent and strong association between the exposure to fluoride and low IQ. The meta-analyses of the case-control studies estimated that the odds ratio of IQ in endemic fluoride areas compared with nonfluoride areas or slight fluoride areas. The summarized weighted mean difference is -4.97 (95%confidence interval [CI] = -5.58 to -4.36; p < 0.01) using a fixed-effect model and -5.03 (95%CI = -6.51 to 3.55; p < 0.01) using a random-effect model, which means that children who live in a fluorosis area have five times higher odds of developing low IQ than those who live in a nonfluorosis area or a slight fluorosis area.
Assuntos
Fluoretos , Inteligência , Criança , China , Humanos , Metanálise como AssuntoRESUMO
Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation.
Assuntos
Cálcio/metabolismo , Epiderme/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Proliferação de Células/efeitos da radiação , Epiderme/metabolismo , Epiderme/ultraestrutura , Hiperplasia/patologia , Lantânio , Masculino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos BALB C , Queimadura Solar/patologiaRESUMO
1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/prevenção & controle , Indazóis/uso terapêutico , Aldeído Redutase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Glicemia/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa Peroxidase/metabolismo , Hemoglobinas Glicadas/metabolismo , Produtos Finais de Glicação Avançada/sangue , Insulina/sangue , Masculino , Bainha de Mielina/patologia , Dor/prevenção & controle , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo , Nervo Sural/patologiaRESUMO
AIM: To investigate the preventive and protective effects of bendazac lysine (BDL) on experimental early diabetic nephropathy (DN) rats. METHODS: After an early DN model was induced by streptozotocin, rats were administered BDL at doses of 100, 200, and 400 mg/kg for 8 weeks. Blood glucose, microalbuminuria, kidney index, total antioxidative capacity, laminin, advanced glycation end products (AGE), aldose reductase (AR) activity, and the relative quantity of transforming growth factor beta1 (TGF- beta1) mRNA were measured by different methods. The ultrastructural morphology was observed by transmission electron microscope. RESULTS: The physical behaviors of early DN rats were hypopraxia, cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated. Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-beta1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated. CONCLUSION: BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.
Assuntos
Nefropatias Diabéticas/prevenção & controle , Indazóis/uso terapêutico , Rim/patologia , Fator de Crescimento Transformador beta/biossíntese , Aldeído Redutase/sangue , Animais , Nefropatias Diabéticas/metabolismo , Eritrócitos/enzimologia , Mesângio Glomerular/patologia , Produtos Finais de Glicação Avançada/metabolismo , Rim/ultraestrutura , Laminina/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1RESUMO
The epidermal permeability barrier appears to be regulated primarily by the lamellar arrangement of lipid bilayers between coneocytes of the stratum corneum and presents a significant barrier to the transdermal delivery of drugs. The aim of the present study was to investigate the effects of oleic acid on the ultrastructure of stratum corneum lipids in rat skin. Wistar rats were treated topically with 10% oleic acid/propylene glycol for 2 h, the structure of stratum corneum was examined by electron microscopy using osmium tetroxide or ruthenium tetroxide postfixation, and the epidermal barrier function was evaluated in a lanthanum tracer study. Ultrastructural examination revealed that there was a marked alteration in the stratum corneum and the tracer penetrated into the intercellular spaces of the stratum corneum after application of oleic acid. These results suggest that ruthenium tetroxide postfixation is a powerful tool for the study of the stratum corneum lipid structure. Oleic acid might increase the epidermal permeability through a mechanism involving the perturbation of stratum corneum lipid bilayers and lacunae formation to enhance transdermal drug delivery.