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1.
Artigo em Inglês | MEDLINE | ID: mdl-38946145

RESUMO

INTRODUCTION: This is the first systematic review and meta-analysis to investigate the effectiveness of the nasal airflow-inducing maneuver (NAIM) in olfactory rehabilitation for total laryngectomy (TL) patients. METHODS: We conducted a systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria required that patients must have undergone a TL with subsequent NAIM training for at least 2 weeks and olfactory evaluation. The impact of NAIM on olfactory outcomes compared to that at baseline was measured. Olfactory measures included the Sniffin' Sticks Test, Smell Disk Test, Scandinavian Odor Identification Test, and Quick Odor Detection Test. The primary outcome measures were the proportion of patients with normosmia at baseline and after intervention. RESULTS: Seven studies from 2000 to 2023 comprising a total of 290 TL patients met the inclusion criteria. The meta-analysis revealed that prior to intervention, the pooled proportion of patients with normosmia was 0.16 (95% confidence interval [CI]: 0.09‒0.27, p = 0.01). After intervention, the same proportion increased to 0.55 (95% CI: 0.45‒0.68, p = 0.001). Among the included patients, 88.3% were initially anosmic or hyposmic, which was reduced to 48.9% after NAIM practice, with 51.1% achieving normosmia. The percent improvement was not found to be significantly associated with the timing of intervention post-TL (p = 0.18). CONCLUSIONS: NAIM increased the proportion of patients who achieved normosmia in TL patients. NAIM stands out as a safe, easily teachable maneuver with promising results. Further efforts are warranted to provide specific recommendations and guidelines for the use of NAIM in clinical practice.

2.
Cureus ; 15(3): e36539, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37090349

RESUMO

Here, we present a case report on internal carotid artery pseudoaneurysm (ICAP) which highlights a rare but potentially life-threatening complication of transsphenoidal pituitary surgery. A 32-year-old male underwent resection of a pituitary tumor and developed a large cerebrospinal fluid (CSF) leak during surgery, which was reconstructed with a fat graft and nasoseptal flap. Postoperatively, he was recovering well and discharged without complications; however, eight days after surgery he returned with massive epistaxis and hematemesis. This was initially managed with endoscopic exploration, nasal packing, and transfusion of blood products. Imaging revealed a pseudoaneurysm on the right internal carotid artery. The patient was started on aspirin and clopidogrel, and a flow diverter stent was placed without complications. Our case emphasizes the importance of prompt recognition and management of vascular injuries such as an internal carotid pseudoaneurysm after transsphenoidal pituitary surgery to prevent catastrophic outcomes.

4.
Int Forum Allergy Rhinol ; 13(3): 216-229, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35938699

RESUMO

BACKGROUND: Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to assess productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS. METHODS: This investigation was a prospective, multi-institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) questionnaire before surgery and approximately 6 months after the procedure. Factors associated with minimal clinical important differences (MCIDs) for productivity and activity impairment were identified. RESULTS: A total of 279 study participants were screened for inclusion, of whom 176 (63.1%) with postoperative follow-up were included in the final cohort. Preoperative productivity and activity impairment were observed in 63.2% and 69.8% of the patients, respectively. Among these patients, postoperative improvement equaling at least 1 MCID was reported in both productivity (76.1%) and activity (76.4%) impairments. Multivariate regression identified sphenoidotomy (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.03-17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR, 8.45; 95% CI, 2.33-30.68) and migraine (OR, 0.35; 95% CI, 0.12-0.96) were associated with differential odds of activity improvement. CONCLUSION: CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared decision-making regarding surgical management for CRS.


Assuntos
Rinite , Sinusite , Humanos , Estudos Prospectivos , Rinite/cirurgia , Rinite/diagnóstico , Sinusite/cirurgia , Sinusite/diagnóstico , Endoscopia/métodos , Doença Crônica , Qualidade de Vida , Resultado do Tratamento
5.
Microbiol Spectr ; 10(6): e0265522, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36416541

RESUMO

Many mechanisms have been proposed to be involved in the formation of bacterial persister cells. In this study, we investigated the impact of dam encoding DNA methylation on persister cell formation in Acinetobacter. We constructed plasmids overexpressing dam encoding DNA-(adenine N6)-methyltransferase and four genes as possibly involved in persistence and introduced them into three A. baumannii strains. For persister cell formation assays, bacteria were exposed to ciprofloxacin, imipenem, cefotaxime, and rifampin, and the transcription levels of the genes were measured by qRT-PCR. In addition, growth curves of strains were determined. We found that all five genes were upregulated following antibiotic exposure. Dam overexpression increased persister cell formation rates and activated the four persister cell-involved genes. Among the four persister cell-involved genes, only RecC overexpression increase persister cell formation rates. While recC-overexpressing strains showed higher growth rates, dam-overexpressing strains showed decreased growth rates. In this study, we revealed that a DNA methyltransferase may regulate persister cell formation in A. baumannii, while RecC seems to mediate epigenetic regulation of persister cell formation. However, Dam and RecC may act at different persister cell formation states. IMPORTANCE Bacterial persister cells are not killed by high concentration of antibiotics, despite its antibiotic susceptibility. It has been known that they may cause antibiotic treatment failure and contribute to the evolution of antibiotic resistance. Although many mechanisms have been suggested and verified for persister cell formation, many remains to be uncovered. In this study, we report that DNA methyltransferase leads to an increase in persister cell formation, through transcriptional activation of several regulatory genes. Our results suggest that DNA methyltransferases could be target proteins to prevent formation of persister cells.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Metiltransferases/genética , Epigênese Genética , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Metilases de Modificação do DNA/genética
6.
Microorganisms ; 10(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36144429

RESUMO

In this study, we investigate the characteristics of two main clones of carbapenemase-producing Klebsiella pneumoniae isolates from South Korea, ST11 and ST307, including carbapenem-susceptible isolates. Antibiotic susceptibility, serotype or wzi allelic type, the presence of virulence genes, and virulence with respect to serum resistance and macrophage internalization were determined for ST11 and ST307 isolates. ST11 isolates had a wide range of characteristics, including serotype and virulence, compared with those of homogeneous ST307 isolates. The wzi14 or K14 type had higher virulence than that of other serotypes among the ST11 isolates, and the homogeneous ST307 isolates showed similar virulence level as that of the wzi14-type ST11 isolates. Our data suggest that it is necessary to monitor not only the introduction and spread of a specific clone, but also its detailed serotype.

7.
Otolaryngol Head Neck Surg ; 166(4): 669-675, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34311614

RESUMO

OBJECTIVE: To create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures that also provides nanoparticle-level protection to patients. STUDY DESIGN: Prospective feasibility study . SETTING: In-person testing with a novel ACM. METHODS: The mask was designed in Solidworks and 3D printed. Measurements were made on 10 healthy volunteers who wore the ACM while reading the Rainbow Passage repeatedly and performing a forced cough or sneeze at 5-second intervals over 1 minute with an endoscope in place. RESULTS: There was a large variation in the number of aerosol particles generated among the volunteers. Only the sneeze task showed a significant increase compared with normal breathing in the 0.3-µm particle size when compared with a 1-tailed t test (P = .013). Both the 0.5-µm and 2.5-µm particle sizes showed significant increases for all tasks, while the 2 largest particle sizes, 5 and 10 µm, showed no significant increase (both P < .01). With the suction off, 3 of 30 events (2 sneeze events and 1 cough event) had increases in particle counts, both inside and outside the mask. With the suction on, 2 of 30 events had an increase in particle counts outside the mask without a corresponding increase in particle counts inside the mask. Therefore, these fluctuations in particle counts were determined to be due to random fluctuation in room particle levels. CONCLUSION: ACM will accommodate rigid and flexible endoscopes plus instruments and may prevent the leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: 2.


Assuntos
COVID-19 , Aerossóis , COVID-19/prevenção & controle , Endoscopia , Humanos , Equipamento de Proteção Individual , Estudos Prospectivos
8.
Otolaryngol Head Neck Surg ; 166(5): 850-857, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34154484

RESUMO

OBJECTIVE: To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols. STUDY DESIGN: Bench testing. SETTING: Mannequin testing. METHODS: The mask was designed in SolidWorks and 3-dimensional printed. Mannequins were fitted with a nebulizer to generate aerosols. Commercial particle counters were used to measure mask performance. RESULTS: The ACM has 2 ports on either side for instruments and endoscopes, a port for a filter, and a port that can evacuate aerosols contained within the mask via a standard suction pump. The mask contained aerosols on a mannequin with and without facial hair when the suction was set to 18.5 L/min. Other types of masks demonstrated substantial aerosol leakage under similar conditions. In a subsequent experiment, the ACM contained aerosols generated by a nebulizer up to the saturation of the particle detector without measurable leakage with or without suction. CONCLUSION: The ACM will accommodate rigid and flexible endoscopes plus instruments and prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: 2.


Assuntos
COVID-19 , Otolaringologia , Aerossóis , Endoscopia , Humanos , Nebulizadores e Vaporizadores
9.
Antibiotics (Basel) ; 10(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34438961

RESUMO

In this study, we investigated the characteristics of KPC-2-producing Klebsiella pneumoniae (KP-Kp) isolates from a hospital in South Korea. Among the 37 KP-Kp isolates, two main clones were identified-ST11 and ST307. ST11 isolates showed higher minimum inhibitory concentrations for carbapenems than ST307 isolates. All ST307 isolates were resistant to gentamicin and trimethoprim-sulfamethoxazole, but ST11 isolates were not. However, most tigecycline-resistant or colistin-resistant isolates belonged to ST11. The two KP-Kp clones showed different combinations of wzi and K serotypes. Plasmids from ST11 KP-Kp isolates exhibited diverse incompatibility types. Serum resistance and macrophage infection assays indicated that ST11 may be more virulent than ST307. The changes in the main clones of KP-Kp isolates over time as well as the different characteristics of these clones, including virulence, suggest the need for their continuous monitoring.

10.
Otolaryngol Head Neck Surg ; 165(6): 899-904, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33685286

RESUMO

OBJECTIVE: Cauterization prevents hemorrhage and optimizes the surgical field during endoscopic sinus surgery but may cause injury to nearby structures. The objective of this study is to examine thermal conductance from cauterization equipment across the skull base. STUDY DESIGN: Cadaver and animal model. SETTING: Surgical skills laboratory of an academic tertiary medical institution. METHODS: A pilot study was conducted with a deidentified cadaver head and expanded to a goat head animal model. Endoscopic dissection was performed to expose the lamina papyracea, ethmoid roof, sphenoid roof, and frontal sinus. Cautery was applied to the frontal sinus of goat heads, and temperatures were measured via thermocouple sensors placed along the intracranial skull base. Surgical instruments studied included monopolar, bipolar, and endoscopic bipolar devices at various power settings. RESULTS: Temperature increase, as averaged across all cautery powers and measurement positions, was highest for the monopolar cautery (17.55 °C) when compared with the bipolar and endoscopic bipolar devices (<2 °C for bipolar, Endo-Pen, Stammberger, and Wormald; P < .001). Monopolar cautery reached 30.86 °C at high power when averaged over all positions (P < .001) as compared with <3 °C for the other instruments. Temperatures rose as power of cautery was increased from low to medium and high. Temperatures decreased as the distance of the thermocouple sensor probe from the cautery origin increased. CONCLUSION: Thermal conductance across the skull base varies depending on equipment and power of cautery, with monopolar resulting in the largest temperature increase. Choice and implementation of cauterization instruments have implications on inadvertent transmission of thermal energy during endoscopic sinus surgery.


Assuntos
Cauterização/instrumentação , Temperatura Alta , Base do Crânio/cirurgia , Instrumentos Cirúrgicos/efeitos adversos , Condutividade Térmica , Animais , Queimaduras/etiologia , Cadáver , Endoscopia , Seio Frontal/lesões , Cabras , Humanos , Modelos Animais , Projetos Piloto
11.
Laryngoscope ; 131(4): E1035-E1037, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32965695

RESUMO

BACKGROUND: There has been a rapid increase in electric motorized scooter (e-scooter) usage after the introduction of dockless, shareable devices. METHODS: Case series from three tertiary hospitals in Los Angeles between May-September 2019. RESULTS: Five patients had skull base fractures and CSF leaks or pneumocephalus after e-scooter accident, none wore helmets. Two patients were treated with observation alone, two patients were treated with lumbar drain or external ventriculostomy placement, and one patient died of their injuries prior to definitive management. CONCLUSION: Without appropriate safety policies in place, the number of such injuries may increase as the use of e-scooters increase. Laryngoscope, 131:E1035-E1037, 2021.


Assuntos
Acidentes de Trânsito , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/terapia , Adolescente , Adulto , Intoxicação Alcoólica , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Feminino , Humanos , Masculino , Veículos Automotores , Pneumocefalia/diagnóstico por imagem , Pneumocefalia/etiologia , Pneumocefalia/terapia , Fraturas Cranianas/diagnóstico por imagem , Fraturas Cranianas/etiologia , Fraturas Cranianas/terapia
12.
Otolaryngol Head Neck Surg ; 165(1): 69-75, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33228442

RESUMO

OBJECTIVE: Nurse practitioners and physician assistants form a growing advanced practice provider (APP) group. We aim to analyze the trends and types of services provided by APPs in otolaryngology. STUDY DESIGN: Cross-sectional study. SETTING: Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use Files, 2012-2017. METHODS: The Medicare database was searched for 13 commonly used otolaryngology-specific Current Procedural Terminology (CPT) codes, and 10 evaluation and management (E/M) codes were evaluated by provider type. Changes in code utilization were compared between physicians and APPs over time. RESULTS: From 2012 to 2017, there was a 51% increase in the number of otolaryngology APPs, compared to a 2.2% increase in physician providers. APPs increased their share of new and established patient visits from 4% to 7%d 11% to 15%, respectively. There was not a significant difference over time in number of patient visits performed annually per provider according to provider type. The increase in number of APP vs physician providers was significantly greater for every procedure except for balloon sinus dilation and tympanostomy tube placement. CONCLUSION: Due to increasing numbers, APPs are accounting for more patient visits and procedures over time. The physician workforce and the numbers of procedures performed per physician have remained relatively stable from 2012 to 2017. Increasing complexity of patients seen and a broader range of procedures offered by work-experienced or postgraduate-trained APPs may further improve access to health care in the face of possible physician shortages.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Medicare , Profissionais de Enfermagem/estatística & dados numéricos , Otolaringologia/organização & administração , Procedimentos Cirúrgicos Otorrinolaringológicos/estatística & dados numéricos , Assistentes Médicos/estatística & dados numéricos , Estudos Transversais , Utilização de Instalações e Serviços , Humanos , Otolaringologia/estatística & dados numéricos , Estados Unidos
13.
Int Forum Allergy Rhinol ; 10(8): 996-1000, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32407593

RESUMO

BACKGROUND: Mast-cell activation syndrome (MCAS) is increasingly recognized. Sinonasal obstruction is common among these patients. There is a paucity of literature describing the characteristics of MCAS and treatment outcomes. METHODS: Retrospective review of 192 patients with nasal congestion July 2017 to May 2019 among 3 providers (1 allergist, 2 rhinologists) was conducted. Suspected MCAS criteria were as follows: (1) at least 2 recurrent severe symptoms in addition to nasal congestion: flushing, pruritus, urticaria, angioedema, wheezing, throat swelling, headache, hypotension, diarrhea; (2) clinical response to medications that target mast cell mediators. Quality of life (QOL) outcomes were quantified using the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Thirty-two patients with nasal congestion were suspected of MCAS. The median age was 47 years; 24 of 32 were female; 13 of 32 had prior history of sinonasal surgery and 11 of 32 allergen immunotherapy. Out of 32, 19 had history of asthma, 10 drug allergy, 11 food allergy, and 10 anaphylaxis. The median number of medications targeting mast cell activation was 4 (range, 2-7). Eleven patients were offered surgery by a rhinologist after adequate medical management. Three of 32 patients showed elevation of serum tryptase. Fourteen completed pretreatment and posttreatment SNOT-22 (4/14 surgery, 10/14 medical management). Pretreatment score was 59.8 ± 6.2 (mean ± standard error [SEM]) and posttreatment score was 42.8 ± 6.7; the difference was statistically and clinically significant (p = 0.0015). Both groups showed a mean 17-point reduction. CONCLUSION: A multidisciplinary approach to the treatment of sinonasal symptoms using both escalation of medical therapy and surgical approaches may improve QOL of patients with suspected MCAS. Consensus criteria for MCAS, which includes elevation in tryptase over baseline during an episode, may exclude the full spectrum of individuals with MCAS from potentially beneficial treatment.


Assuntos
Mastocitose , Qualidade de Vida , Feminino , Humanos , Mastócitos , Mastocitose/diagnóstico , Mastocitose/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Triptases
14.
Laryngoscope ; 130(12): 2785-2790, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31922610

RESUMO

BACKGROUND: A bioabsorbable nasal valve implant (NVI) was introduced in 2016 as a minimally invasive solution to nasal valve collapse. Historically the introduction of less invasive procedures performable in-office has resulted in an increase in volume. Our objective is to evaluate this trend as it relates to nasal vestibular repair, and its impact on healthcare utilization. METHODS: We interrogated the Medicare Part B national database for nasal vestibular repair (CPT code: 30465), Unlisted nasal procedure (30999) and septoplasty (30520) from 2010 to 2017. Septoplasty was used as a surrogate for overall nasal procedural rate. Linear regression modeling was used to examine the changes in reported vestibular repair rate adjusting for septoplasty rate. RESULTS: In the Medicare population, the rate of septoplasty was stable from 2010 to 2017, increasing from 26,962 to 30,194 at an annual rate of 1.5%. Coding for unlisted nasal procedure increased from 272 to 333 at an adjusted annual rate of 1.1% over this time period. Coding for nasal vestibular repair increased from 2026 to 5331 over this interval at an adjusted annual rate of 0.9% from 2010 to 2016 but significantly increased to 5% between 2016 to 2017 (P < .0001). CONCLUSION: The reported volume of nasal vestibular repair increased significantly in the year following Food and Drug Administration approval of NVIs. In the absence of a corresponding increase in septoplasty, this temporal relationship suggests that the introduction of NVIs impacted the utilization of this procedural code. LEVEL OF EVIDENCE: N/A Laryngoscope, 2020.


Assuntos
Implantes Absorvíveis , Obstrução Nasal/cirurgia , Septo Nasal/cirurgia , Padrões de Prática Médica/tendências , Idoso , Feminino , Humanos , Masculino , Medicare , Estados Unidos
15.
Materials (Basel) ; 12(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671519

RESUMO

We introduce a new tongue prosthetic assist device (TPAD), which shows the first prosthetic application for potential treatment of swallowing difficulty in dysphagia patients. The native tongue has a number of complex movements that are not feasible to mimic using a single mechanical prosthetic device. In order to overcome this challenge, our device has three key features, including (1) a superelastic nitinol structure that transfers the force produced by the jaws during chewing towards the palate, (2) angled composite tubes for guiding the nitinol strips smoothly during the motion, and (3) highly stretchable thin polymeric membrane as a covering sheet in order to secure the food and fluids on top of the TPAD for easy swallowing. A set of mechanical experiments has optimized the size and angle of the guiding tubes for the TPAD. The low-profile TPAD was successfully placed in a cadaver model and its mobility effectively provided a simplistic mimic of the native tongue elevation function by applying vertical chewing motions. This is the first demonstration of a new oral device powered by the jaw motions in order to create a bulge in the middle of the mouth mimicking native tongue behavior.

16.
Otolaryngol Head Neck Surg ; 154(1): 104-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26424747

RESUMO

OBJECTIVE: Identify prognostic factors after salvage surgery for recurrent sinonasal malignancy (SNM). STUDY DESIGN: Case series with chart review. SETTING: University of Pittsburgh Medical Center. SUBJECTS: Forty-two patients who underwent curative surgery for locally recurrent SNM ± adjuvant therapy from June 5, 2000, to December 19, 2012. Patients without follow-up were excluded. METHODS: Chart review with established prognostic indicators for primary malignancies. Statistical analysis included Kaplan-Meier log-rank test, Fisher's exact test, Student's t test, and Cox regression. RESULTS: Forty-two patients met inclusion criteria: 38.5% developed a second recurrence, and 21.4% had metastases following treatment. The average disease-free interval (DFI) was 26.9 months (range, 2-90 months). DFI was significantly affected by ethmoid versus nonethmoid site (P = .049), histology (P = .012), carotid artery involvement (P = .008), perineural extension (P = .006), and clival invasion (P = .015). The overall survival rates at 6 months, 12 months, and 5 years following surgery were 83.3%, 69%, and 47.6%, respectively. Survival was affected by histology (P = .014), stratified grade (P = .042), tumor extension into the orbit (P = .019), carotid artery (P = .001), perineural space (P = .028), and clivus (P = .022). Complications occurred in 28.6% of patients and were associated with histology (P = .04). Length of hospital stay related to treatment was affected by histology (P = .009), grade (P = .013), and postoperative complication (P < .001). The median percentage of time hospitalized was 8%, and 43% of patients who died within 12 months spent >10% of their remaining days in the hospital. CONCLUSION: High-risk histologic subtype (melanoma, sinonasal undifferentiated carcinoma, adenocarcinoma, neuroendocrine cancer, sarcoma, and squamous cell carcinoma), grade, and orbital and skull base involvement negatively affect survival and/or DFI for patients with local recurrence of SNM. Improved stratification of patients can be used to guide decision making for patients with recurrent SNM and to avoid inappropriate surgery.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Nasais/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Nasais/mortalidade , Neoplasias dos Seios Paranasais/mortalidade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida
17.
Radiat Res ; 180(2): 189-204, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23862693

RESUMO

Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSOD(tet)) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSOD(tet/tet) cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of MnSOD(tet/tet) cells increased MnSOD levels and radioresistance from ñ of 2.79 ± 1.04 to 8.69 ± 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSOD(tet/tet) cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-ß, Nrf2 and NF-κB and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSOD(tet/tet) mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation.


Assuntos
Linhagem Celular/efeitos da radiação , Raios gama/efeitos adversos , Tolerância a Radiação/genética , Células Estromais/efeitos da radiação , Superóxido Dismutase/fisiologia , Animais , Medula Óssea , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular/enzimologia , Células Clonais/enzimologia , Células Clonais/efeitos da radiação , Ensaio de Unidades Formadoras de Colônias , Quebras de DNA/efeitos da radiação , Doxiciclina/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/efeitos da radiação , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Mitocôndrias/enzimologia , Mutagênese Sítio-Dirigida , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/biossíntese , NF-kappa B/genética , Plasmídeos/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Células Estromais/enzimologia , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genética , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta/genética
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