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1.
J Craniofac Surg ; 34(8): e781-e785, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37643112

RESUMO

PURPOSE: The purpose of this study was to analyze the patients clinically who underwent reoperation after certain Orthognathic procedures, and to assess the reoperation rate. Furthermore, the authors also evaluated the incidence of intraoperative and postoperative complications that led to the need for reoperation. METHODS: Total 526 patients were selected who underwent Orthognathic surgery between July 2008 and February 2022 at the Department of Oral and Maxillofacial Surgery in Pusan National University Dental Hospital by single surgeon. All the patients information were extracted from electronic database of our university. Demographic, radiologic, intraoperative, and postoperative data were recorded and compiled. RESULTS: Out of 526 patients, 265 (50.3%) were males and 261 (49.6%) were females. The total number of patients who showed complication is 89 (16.9%) and the patients who underwent reoperation are 17 (3.2%). The common complications that occurred were postoperative sensory disturbance (31; 5.8%), unwanted fractures (17; 3.2%), intraoperative nerve injury (11; 2%), wound dehiscence (11; 2%), infection (10; 1.9%), tooth injury (2; 0.3%), and others (18; 3.4%). The serious complications that led to reoperation include severe bleeding (6; 1.1%), unesthetic results (5; 0.9%), non-union of maxilla (4; 0.7%), and failed osteosynthesis (2; 0.3%). After 2018, all the orthognathic surgeries were performed with the help of virtual surgical planning. After application of virtual surgical planning, the number of patients with complications statistically decreased. CONCLUSION: The present study showed that the reoperation rate after orthognathic surgery was low, this rate was more decreased after applying 3-dimensional virtual surgery and 3-dimensional printed plate, especially in unesthetic cases.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Masculino , Feminino , Humanos , Estudos Retrospectivos , Procedimentos Cirúrgicos Ortognáticos/métodos , Reoperação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
J Craniofac Surg ; 34(1): 358-361, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36100976

RESUMO

PURPOSE: To determine the accuracy of planned maxillary positioning by virtual surgery by comparing planned and actual postoperative outcomes. MATERIALS AND METHODS: Twenty patients who underwent 2-jaw orthognathic surgery performed by a single surgeon from May 2017 to December 2020 were the subjects of this retrospective study. The coordinates of reference points in horizontal, sagittal, and coronal planes as determined by virtual surgery were compared with those of actual surgical outcomes. The reference points used were as follows: #16 mesiobuccal cusp tip (#16), #26 mesiobuccal cusp tip (#26), and #11 mesial tip (U1); anterior nasal spine; and posterior nasal spine. Three-dimensional linear distances between the reference point on which virtual surgery was performed and the reference point after the actual operation was calculated. RESULTS: Of the 20 patients, there were 11 males and 9 females of average age 20.65±2.41 years. Three-dimensional printed wafers had high accuracy with a maximum difference of 0.3 mm. No significant difference was observed in horizontal or coronal planes for any reference point, but a significant difference was observed in the sagittal plane. However, positional differences between planned and actual reference points were all <1 mm. CONCLUSIONS: Virtual surgical planning and 3-dimensional printed wafer achieved excellent maxillary positioning accuracies after orthognathic surgery.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Cirurgia Assistida por Computador , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Imageamento Tridimensional , Procedimentos Cirúrgicos Ortognáticos/métodos , Maxila/diagnóstico por imagem , Maxila/cirurgia , Internet , Cirurgia Assistida por Computador/métodos
3.
Int J Med Sci ; 19(12): 1732-1742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313226

RESUMO

Background: This experimental research aimed to determine whether No-ozone Cold Plasma (NCP) has regenerative effect on crushed injured sensory nerves in a rat model (Wistar A) and to evaluate whether NCP can be used as an alternative treatment method for sensory nerve injury in the oral-maxillofacial region. Methods: A total of 10 Wistar A rats were used for this experiment. They were divided into three groups according to whether the mental nerve of the left mandible was injured and NCP was applied or not: group 1 (n=3) (non-mental nerve damage, non-MD) - the left mental nerve was exposed and non-damaged; group 2 (n=3) (mental nerve damage, MD) - the left mental nerve was exposed and damaged, NCP was not applied; and group 3 (n=4) (mental nerve damage and NCP, MD-NCP) - the left mental nerve was exposed and damaged, NCP was applied with regular intervals (three times a week). Results: For the behavior analysis, von Frey test was used. Furthermore, the nerve tissues were examined with hematoxylin and eosin (H&E) staining, and the extent of neurorecovery was evaluated with the immunofluorescence staining of certain markers. The behavioral analysis showed that the function recovery sensory nerve was faster in group 3 (MD-NCP). In the histomorphologic and immunofluorescence analyses, the expression of the factors involved in neurorecovery was much higher in group 3 than in group 2 (MD). Conclusions: The expeditious recovery of sensory nerve function as well as the higher expression of the factors indicating nerve function recovery in the NCP-treated group suggest that NCP has a positive effect on regeneration after sensory nerve crushing injury. Therefore, in the case of sensory impairment of the oral-maxillofacial region, no-ozone cold plasma can be applied for therapeutic effect.


Assuntos
Lesões por Esmagamento , Traumatismos do Nervo Mandibular , Ozônio , Traumatismos dos Nervos Periféricos , Gases em Plasma , Ratos , Animais , Nervo Isquiático/lesões , Regeneração Nervosa , Gases em Plasma/uso terapêutico , Ozônio/farmacologia , Ozônio/uso terapêutico , Ratos Wistar , Traumatismos dos Nervos Periféricos/tratamento farmacológico
4.
J Craniofac Surg ; 33(5): 1529-1532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35119401

RESUMO

BACKGROUND: During bimaxillary surgery, manipulation of the pterygoid plate is required to facilitate movement of the maxilla. This study examined the complications that occurred after handling the pterygoid plate during a Le Fort I osteotomy. PATIENTS AND METHODS: This study compared and analyzed complications according to the pterygoid plate handling method in 80 patients who underwent bimaxillary surgery at Pusan National University Dental Hospital from December 2015 to July 2020. The pterygoid plate was fractured or removed intentionally only if it interfered with the maxilla. Otherwise, it was not treated. The complications during surgery and the follow-up period were investigated. RESULTS: Fourteen patients experienced complications, of which excessive bleeding, hearing problems, and nonunion were encountered in 10, 2, and 2 patients, respectively. Of the 10 patients with excessive bleeding patients, the pterygoid plate was manipulated in 8 patients, which was controlled during surgery. Two patients complained of hearing loss with ear congestion immediately after surgery; both patients improved spontaneously within 1 month. Two nonunion patients underwent plate refixation at least 6 months postoperatively, and normal healing was achieved afterward. CONCLUSIONS: Fracture and removal of the pterygoid plate during orthognathic surgery did not significantly affect the occurrence of complications during and after surgery.


Assuntos
Procedimentos Cirúrgicos Ortognáticos , Osteotomia de Le Fort , Osso Esfenoide , Placas Ósseas , Humanos , Maxila/anatomia & histologia , Maxila/cirurgia , Doenças Maxilares/cirurgia , Osteotomia de Le Fort/efeitos adversos , Osteotomia de Le Fort/métodos , Osso Esfenoide/anatomia & histologia , Osso Esfenoide/cirurgia
5.
J Craniofac Surg ; 33(6): e546-e550, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35142736

RESUMO

PURPOSE: The aim of this study was to review retrospectively the functional recoveries of subcondylar fracture patients that underwent open reduction surgery using an extraoral approach or an intraoral approach using a trans-buccal trocar and involving ramus buccal decortication. MATERIALS AND METHODS: Of 47 patients with mandibular condyle fracture who visited Pusan National University Dental Hospital Department of Oral and Maxillofacial Surgery between May 2015 and November 2020, 38 patients underwent open reduction and were classified according to the surgical method used. Preauricular, submandibular, and retro-mandibular approaches were all classified as extraoral approaches condyle fractures were classified as described by Spiessl and Schroll (1972). Distances between bone fragments on panorama radiographs before and after surgery were measured. RESULTS: Thirty-eight patients were included in this study, 9 patients received subcondylar fracture surgery. Open reduction surgery using an extraoral approach had a greater mean operation time than the intraoral approach using a trocar. Of the 17 patients treated with an intraoral approach, the average distance between bone fragments right after surgery was 1.27 ± 1.41mm, which was significantly greater than that of the extraoral approach (0.72 ± 0.35 mm). CONCLUSIONS: Favorable results can be obtained by mandibular condylar fracture surgery through an intraoral approach using a trans-buccal trocar with ramus buccal decortication. This technique minimizes scarring, secures accessibility using a trocar, and sufficiently secures the field of view through buccal cortical bone reduction.


Assuntos
Fixação Interna de Fraturas , Fraturas Mandibulares , Fixação Interna de Fraturas/métodos , Humanos , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Estudos Retrospectivos , Instrumentos Cirúrgicos
6.
Morphologie ; 105(351): 267-274, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33309198

RESUMO

OBJECTIVE: Colorectal carcinoma (CRC) is the third most common cancer in the world and fifth most common cancer in India. To understand the extent of perineural invasion (PNI) in CRC it is essential to study the morphology of enteric glial cells (EGCs). The aim of the study was to analyze the numerical density of EGCs and area of myenteric ganglia (MG) in the colonic tissue samples collected from CRC patients. MATERIAL AND METHODS: Fifteen intraoperative tissue specimens were collected from the tumor site and 2cm proximal to the upper extent of tumor. The samples were divided into four groups: group 1 (n=15): proximal tumor free colonic tissue; group 2 (n=3): well-differentiated; group 3 (n=8): moderately differentiated; group 4 (n=4): poorly differentiated adenocarcinoma. After processing the tissues were subjected to hematoxylin and eosin staining. The anti-S100ß and anti-GFAP antibodies were used to observe the EGCs. RESULTS: In the H&E stained sections the number of myenteric ganglia appeared to be decreasing with increasing grade of adenocarcinoma. Immunostaining showed significant decreasing pattern in the numerical density of EGCs per myenteric ganglion and mean area of myenteric ganglia in relation to the thickness of circular muscle, corresponding to the increasing grades of adenocarcinoma. The morphology of the EGCs remained unaltered in the colonic tissue adjacent to the tumor site. CONCLUSION: Significant loss of EGCs and neurodegeneration corresponded with the grade of tumor emphasizing on its prognostic value. The PNI was not seen in the clear margin proximal to the tumor site.


Assuntos
Neoplasias Colorretais , Plexo Mientérico , Humanos , Índia , Neuroglia
7.
Annu Rev Genet ; 46: 371-96, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22974305

RESUMO

The fruit fly, Drosophila melanogaster, is an excellent organism for the study of the genetic and molecular basis of metazoan development. Drosophila provides numerous tools and reagents to unravel the molecular and cellular functions of genes that cause human disease, and the past decade has witnessed a significant expansion of the study of neurodegenerative disease mechanisms in flies. Here we review the interplay between oxidative stress and neuronal toxicity. We cover some of the studies that show how proteasome degradation of protein aggregates, autophagy, mitophagy, and lysosomal function affect the quality control mechanisms required for neuronal survival. We discuss how forward genetic screens in flies have led to the isolation of a few loci that cause neurodegeneration, paving the way for large-scale systematic screens to identify such loci in flies as well as promoting gene discovery in humans.


Assuntos
Drosophila melanogaster/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo , Ubiquitina/metabolismo , Animais , Autofagia , Modelos Animais de Doenças , Drosophila melanogaster/genética , Humanos , Longevidade/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transmissão Sináptica , Ubiquitina/genética
8.
Transfus Med ; 24(1): 45-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25121159

RESUMO

BACKGROUND: Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects. MATERIALS AND METHODS: Within a 19-month period, baseline and weekly samples from 15 CPDA-1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin. RESULTS: One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0·50, P < 0·01) of storage; four units increase at 2 weeks (r2 = 0·64, P < 0·001) and 3 weeks (r2 = 0·51, P < 0·01) of storage; six units at 4 weeks (r2 = 0·53, P < 0·01) of storage. Baseline whole blood haemoglobin showed a moderate association with baseline potassium (r2 = 0·36, P < 0·05) and 2-week potassium (r2 = 0·35, P < 0·05) values. CONCLUSION: For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the 'first-in-first-out' (FIFO) policy with 'early release of blood-bags with high initial potassium' might be helpful in improving the release of suitable blood units from blood-banks.


Assuntos
Armazenamento de Sangue/métodos , Preservação de Sangue/métodos , Potássio/sangue , Preservação de Sangue/instrumentação , Feminino , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/prevenção & controle , Masculino , Fatores de Tempo , Reação Transfusional
9.
Maxillofac Plast Reconstr Surg ; 46(1): 20, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861059

RESUMO

BACKGROUND: Odontogenic maxillary sinusitis (OMS) is widely acknowledged in both the dentistry and otolaryngology fields. Recently, iatrogenic odontogenic maxillary sinusitis cases can be encountered frequently. The purpose of this study was to evaluate the effect of intraoral sinus irrigation using the small lateral window approach in patients with odontogenic maxillary sinusitis by comparing pre- and postoperative volumetric measurement of CBCT and symptoms. We surveyed 21 patients who visited the Oral and Maxillofacial Surgery Department at PNUDH from 2016 to 2022. All the patients' information was extracted from an electronic database. The patients with a follow-up period of 2 months or more were included. The three-dimensional volumetric measurement was performed using the ImageJ program (National Institute of Health, University of Wisconsin). RESULTS: Among 21 patients, 16 (76.1%) were male, and 5 (23%) were female. The most common type of surgery was general anesthesia (16 cases) in which oroantral fistula was present in 7 cases. In the causes of maxillary sinusitis, there were seven implant-related patients, five patients of tooth extraction, seven patients of bone grafting, and two patients in other groups. Radiographic opacity decreased by 40.15% after sinus irrigation especially in bone graft and tooth extraction cases. Clinically, symptoms improved in 17 patients (80.9%). CONCLUSION: By this study, it can be concluded that maxillary sinus irrigation using the small lateral window approach is a clinically and radiologically effective treatment method for odontogenic maxillary sinusitis.

10.
BMC Complement Med Ther ; 24(1): 46, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245726

RESUMO

BACKGROUND: This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis. METHODS: Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected. RESULTS: NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells. CONCLUSION: These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.


Assuntos
Neuroblastoma , Ozônio , Gases em Plasma , Humanos , Espécies Reativas de Oxigênio/metabolismo , Caspase 3/metabolismo , Gases em Plasma/farmacologia , Gases em Plasma/uso terapêutico , Ozônio/farmacologia , Ozônio/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Linhagem Celular Tumoral , Apoptose , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico
11.
Kathmandu Univ Med J (KUMJ) ; 10(39): 56-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23434964

RESUMO

BACKGROUND: Psychological stress is common in medical school and associated with depression. Medical education is grooming in Nepal, but only few studies are done concerning mental health of medical students. OBJECTIVE: To assess the prevalence of depression among medical students at different levels of education and find about their stressors. METHODS: A cross sectional, questionnaire-based survey was carried out among the undergraduate medical students of B.P.Koirala Institute of Health Sciences, Nepal. 50 students each from Bachelor of Medicine and Bachelor of Surgery (MBBS) first and third year were enrolled in the study conducted between November 2008 to January 2009. The depression levels were assessed using Zung depression scale. Students were asked to complete the questionnaire and then the depression levels calculated .The stress inducing factors during their course of medical education were also assessed. RESULTS: The overall prevalence of depression among the students was 29.78 percent. The prevalence of depression in first and third year was 36.74and 22.22 percent respectively. The prevalence of depression was 32.43 percent among female students versus 28.07 percent in male students. Both first and third year students gave high ratings to academic stress and hectic lifestyle as the main stress inducing factors. CONCLUSION: The prevalence of depression is seen especially in the first year medical students. So, attempts should be made to alleviate the stressors right from the time they join medical school. Since academic stress proved to be one of the major factors, measures to make the academic curriculum more student-friendly are suggested.


Assuntos
Depressão/epidemiologia , Educação de Graduação em Medicina/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Estudantes de Medicina/psicologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Nepal/epidemiologia , Prevalência , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Adulto Jovem
12.
Sci Rep ; 12(1): 15868, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151253

RESUMO

Among the various methods, Non Thermal Plasma (NTP) has been recently introduced and is being studied to recover the damaged nerve. In the recent years, several studies have suggested that NTP accelerates nerve cell regeneration, but the mechanism remains unknown. This study evaluated the effect of NTP on neuronal proliferation in SH-SY5Y (Human neuroblastoma cells) cells differentiated by retinoic acid (RA) and investigated the mechanism by which NTP promotes cell proliferation. We analyzed the morphology of differentiated SH-SY5Y cells, and performed western blot analysis and reverse transcription polymerase chain reaction (RT-PCR). Immunofluorescence analysis was performed in an in vivo study by categorizing Wistar A rats into three groups: non-nerve damage (Non-ND), nerve damage (ND), and nerve damage + NTP treatment (ND + NTP). The cell morphology analysis revealed that the number of cells increased and axonal elongation progressed after NTP treatment. In addition, western blots indicated that tau expression increased significantly after NTP treatment. The RT-PCR results revealed that the expression of tau, wnt3a, and ß-catenin increased after NTP treatment. The in vivo immunofluorescence assay showed that NTP increased the markers for tau and S100B while regulating the over-expression of MAP2 and GAP43. NTP treatment accelerated cell proliferation and regeneration of damaged neurons in differentiated SH-SY5Y cells. These results establish the fact of NTP as a noninvasive and effective treatment for nerve injury.


Assuntos
Neuroblastoma , Gases em Plasma , Animais , Axônios/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neuroblastoma/metabolismo , Neurônios/metabolismo , Gases em Plasma/farmacologia , Ratos , Ratos Wistar , Tretinoína/metabolismo , Tretinoína/farmacologia , beta Catenina/metabolismo
13.
Phys Rev Lett ; 107(4): 047206, 2011 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-21867039

RESUMO

We report on the first systematic study of spin transport in bilayer graphene (BLG) as a function of mobility, minimum conductivity, charge density, and temperature. The spin-relaxation time τ(s) scales inversely with the mobility µ of BLG samples both at room temperature (RT) and at low temperature (LT). This indicates the importance of D'yakonov-Perel' spin scattering in BLG. Spin-relaxation times of up to 2 ns at RT are observed in samples with the lowest mobility. These times are an order of magnitude longer than any values previously reported for single-layer graphene (SLG). We discuss the role of intrinsic and extrinsic factors that could lead to the dominance of D'yakonov-Perel' spin scattering in BLG. In comparison to SLG, significant changes in the carrier density dependence of τ(s) are observed as a function of temperature.

14.
Cancer Res ; 61(17): 6388-93, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11522631

RESUMO

NO-mediated inhibition of base excision DNA repair may potentiate oxidativeDNA damage in cells and could be relevant to carcinogenesis associated with chronic inflammation. Because 8-oxoguanine, a ubiquitous oxidative DNA lesion, is repaired predominantly by human 8-oxoguanine glycosylase (hOgg1), our aim was to determine whether NO directly inhibits its repair activity. Neither induction of NO-generating enzyme inducible NO synthase nor treatment with S-nitroso-N-acetyl-D-L-pencillamine altered expression of hOgg1 in a human cholangiocarcinoma cell line (KMBC). In contrast, both treatments completely inhibited activity of hOgg1 immunoprecipitated from KMBC cells overexpressing hOgg1 and in a cell-free system. Both NO and peroxynitrite were capable of inhibiting hOgg1 activity. Inhibition of hOgg1 protein was characterized by formation of S-nitrosothiol adducts and loss/ejection of zinc ions. Our data indicate that NO, an inflammatory mediator, directly inhibits a key base excision repair enzyme (hOgg1) responsible for base excision repair of 8-oxoguanine. These data support the concept that NO-mediated inhibition of DNA contributes to the mutagenic environment of chronic inflammation.


Assuntos
Reparo do DNA/efeitos dos fármacos , Guanina/análogos & derivados , N-Glicosil Hidrolases/antagonistas & inibidores , Óxido Nítrico/farmacologia , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Dano ao DNA , Reparo do DNA/fisiologia , DNA Complementar/genética , DNA-Formamidopirimidina Glicosilase , Expressão Gênica , Guanina/metabolismo , Humanos , N-Glicosil Hidrolases/genética , N-Glicosil Hidrolases/metabolismo , Nitratos/metabolismo , Nitratos/farmacologia , Nitrosação/efeitos dos fármacos , Oxidantes/farmacologia , Oxirredução , Testes de Precipitina , Transfecção , Células Tumorais Cultivadas , Zinco/metabolismo
15.
Cancer Res ; 60(1): 184-90, 2000 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-10646872

RESUMO

Chronic infection and inflammation are risk factors for the development of cholangiocarcinoma, a highly malignant, generally fatal adenocarcinoma originating from biliary epithelia. However, the link between inflammation and carcinogenesis in these disorders is obscure. Because nitric oxide (NO) is generated in inflamed tissues by inducible nitric oxide synthase (iNOS) and because DNA repair proteins are potentially susceptible to NO-mediated nitrosylation, we formulated the hypothesis that inflammatory cytokines induce iNOS and sufficient NO to inhibit DNA repair enzymes leading to the development and progression of cholangiocarcinoma. iNOS and nitrotyrosine were demonstrated in 18/18 cholangiocarcinoma specimens. Furthermore, iNOS and NO generation could be induced in vitro by inflammatory cytokines (mixture of interleukin-1beta, IFN-gamma, and tumor necrosis factor alpha) in three human cholangiocarcinoma cell lines. NO-dependent DNA damage as assessed by the comet assay was demonstrated during exposure of the three cholangiocarcinoma cell lines to cytokines. Moreover, global DNA repair activity was inhibited by 70% by a NO-dependent process after exposure of cells to cytokines. Our data indicate that activation of iNOS and excess production of NO in response to inflammatory cytokines cause DNA damage and inhibit DNA repair proteins. NO inactivation of DNA repair enzymes may provide a link between inflammation and the initiation, promotion, and/or progression of cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/metabolismo , Dano ao DNA , Reparo do DNA , Proteínas de Neoplasias/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Animais , Colangiocarcinoma/genética , Colangite/metabolismo , Indução Enzimática , Humanos , Interferon gama/farmacologia , Interleucina-1/farmacologia , Óxido Nítrico Sintase Tipo II , Ratos , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia
16.
Oncogene ; 35(8): 1058-65, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-25961933

RESUMO

In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma as well as vesicular membranes and critically influences metastatic behavior. The soluble, cleaved N-terminal domain of V-ATPase a2 isoform is associated with in vitro induction of tumorigenic characteristics in macrophages. This activity led us to further investigate its in vivo role in cancer progression by inhibition of a2 isoform (a2V) in tumor cells and the concomitant effect on tumor microenvironment in the mouse 4T-1 breast cancer model. Results showed that macrophages cocultivated with a2V knockdown (sh-a2) 4T-1 cells produce lower amounts of tumorigenic factors in vitro and have reduced ability to suppress T-cell activation and proliferation compared with control 4T-1 cells. Data analysis showed a delayed mammary tumor growth in Balb/c mice inoculated with sh-a2 4T-1 cells compared with control. The purified CD11b(+) macrophages from sh-a2 tumors showed a reduced expression of mannose receptor-1 (CD206), interleukin-10, transforming growth factor-ß, arginase-1, matrix metalloproteinase and vascular endothelial growth factor. Flow cytometric analysis of tumor-infiltrated macrophages showed a significantly low number of F4/80(+)CD11c(+)CD206(+) macrophages in sh-a2 tumors compared with control. In sh-a2 tumors, most of the macrophages were F4/80(+)CD11c(+) (antitumor M1 macrophages) suggesting it to be the reason behind delayed tumor growth. Additionally, tumor-infiltrating macrophages from sh-a2 tumors showed a reduced expression of CD206 compared with control whereas CD11c expression was unaffected. These findings demonstrate that in the absence of a2V in tumor cells, the resident macrophage population in the tumor microenvironment is altered which affects in vivo tumor growth. We suggest that by involving the host immune system, tumor growth can be controlled through targeting of a2V on tumor cells.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/imunologia , Macrófagos , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Feminino , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células Tumorais Cultivadas , Microambiente Tumoral , ATPases Vacuolares Próton-Translocadoras/metabolismo
17.
Mutat Res ; 412(2): 195-205, 1998 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-9539974

RESUMO

Precancerous lesions of cervix, commonly known as dysplasia, present a complex problem because of their biological behavior. Increased genetic instability, either inherent or induced by some external mutagen, is considered as a primary event or a predisposing factor to neoplastic transformation. The relationship between genetic instability and susceptibility towards cervical cancer was evaluated with the comet or single cell gel electrophoresis (SCGE) assay. Among precancerous individuals, genomic instability was observed in cervical epithelial cells and peripheral blood leukocytes. The mean basal DNA damage and mean susceptibility to DNA damage by the mutagen (MNNG) treatment increased whereas repair capacity decreased with progression of the disease in a stepwise manner. Inter and intra individual variability was maximum in cancerous group. Risk was estimated by giving a predictive value for each precancerous individual. In combination with morphological, biochemical, and cytogenetic parameters, the SCGE assay may serve as a novel tool to predict the fate of cervical dysplasia.


Assuntos
Dano ao DNA , Testes de Mutagenicidade , Lesões Pré-Cancerosas/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Metilnitronitrosoguanidina , Pessoa de Meia-Idade , Mutagênicos , Lesões Pré-Cancerosas/sangue , Prognóstico , Medição de Risco , Displasia do Colo do Útero/sangue
18.
Oncogene ; 33(49): 5649-54, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-24362525

RESUMO

Macrophage polarization contributes to distinct human pathologies. In tumors, a polarized M2 phenotype called tumor-associated macrophages (TAMs) are associated with promotion of invasion and angiogenesis. In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma/vesicular membranes and critically influences the metastatic behavior. In addition, the soluble, cleaved N-terminal domain of a2 isoform of V-ATPase (a2NTD) is associated with in vitro induction of pro-tumorigenic properties in monocytes. This activity of a2 isoform of V-ATPase (a2V) caused us to investigate its role in cancer progression through the evaluation of the immunomodulatory properties of a2NTD. Here, we present direct evidence that surface expression of V-ATPase is associated with macrophage polarization in tumor tissue. Macrophages from BALB/c mice (peritoneal/bone marrow derived) were stimulated with recombinant a2NTD in both ex vivo and in vivo systems and evaluated for TAM characteristics. a2V was highly expressed in tumor tissues (breast and skin) as well as on the surface of tumor cell lines. The a2NTD-stimulated macrophages (a2MΦ) acquired TAM phenotype, which was characterized by elevated expression of mannose receptor-1, Arginase-1, interleukin-10 and transforming growth factor-ß. a2MΦ also exhibited increased production of other tumorigenic factors including matrix metalloproteinase-9 and vascular endothelial growth factor. Further, a2MΦ were cocultured with mouse B-16F0 melanoma cells for their functional characterization. The coculture of these a2MΦ subsequently increased the invasion and angiogenesis of less invasive B-16F0 cells. When cocultured with naive T cells, a2MΦ significantly inhibited T-cell activation. The present data establish the role of V-ATPase in modulating a macrophage phenotype towards TAMs through the action of a2NTD, suggesting it to be a potential therapeutic target in cancer.


Assuntos
Regulação Enzimológica da Expressão Gênica , Macrófagos/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Ativação Linfocitária , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/metabolismo , Invasividade Neoplásica , Neoplasias/imunologia , Neoplasias/metabolismo , Neovascularização Patológica , Fenótipo , Estrutura Terciária de Proteína , Proteínas Recombinantes/metabolismo , Linfócitos T/citologia
19.
J Dev Orig Health Dis ; 3(3): 166-72, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23050071

RESUMO

Little is known about the relationship between low birth weight (BW), as a marker of under-nutrition in utero, and childhood body mass index (BMI) and adiposity parameters, including skinfold thickness, abdominal subcutaneous (SAT) and visceral adipose tissues (VAT) and intramyocellular accumulation of lipids (IMCL). The EPOCH Study (Exploring Perinatal Outcomes among Children) explored the association between BW and markers of adiposity in contemporary, multi-ethnic children from Colorado. A total of 442 youth age 6-13 years (50% male, mean age 10.5 years) had anthropometric measurements, abdominal SAT and VAT measured by magnetic resonance imaging and IMCL deposition in the soleus muscle measured by nuclear magnetic resonance spectroscopy. BW and gestational age were ascertained from an electronic perinatal database. A weak positive association between BW and current BMI (P=0.05) was seen, independent of demographic, perinatal, socio-economic and current lifestyle factors. When adjusted for current BMI, every one standard deviation decrease in BW (~500 g), was associated with a 8.8 cm(2) increase in SAT, independent of potential confounders. In conclusion, in a contemporary cohort of youth, BW was positively, but weakly, associated with BMI and inversely, though weakly, associated with SAT, independent of current BMI. There were no significant associations between BW and waist circumference, skinfolds, VAT and IMCL. Our results provide some support to the hypothesis that under-nutrition in utero, as reflected by lower BW, is associated with lower overall childhood body size, but an increased propensity for abdominal adiposity, reflected in this young age-group, predominantly as subcutaneous fat.

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