RESUMO
Radiation exposure is an undeniable health threat encountered in various occupations and procedures. High energy waves in ionizing radiation cause DNA damage and induce reactive oxygen species (ROS) production, which further exacerbate DNA, protein, and lipid damage, increasing risk of mutations. Although endogenous antioxidants such as superoxide dismutase have evolved to upregulate and neutralize ROS, exogenous dietary antioxidants also have the potential to combat ionizing radiation (IR)-induced ROS production. We evaluated a cocktail of ingredients (AOX) purported to have antioxidant and mitochondrial protective properties on the acute effects of IR. We show that IR stimulates DNA damage through phosphorylation of DNA repair proteins in the heart, brain, and liver of mice. AOX showed partial protection in brain and liver, through a lack of significant activation in given repair proteins. In addition, AOX attenuated the IR-induced increase in NF-kß mRNA and protein expression in brain and liver. Lastly, cytochrome c oxidase complex transcripts were significantly higher in heart and brain following radiation, which was also diminished by prior ingestion of AOX. Together, our findings suggest that a multi-ingredient AOX supplement may attenuate the IR-induced cellular damage response and represents a feasible and cost-effective preventative supplement for at-risk populations of radiation exposure.
Assuntos
Antioxidantes , Radiação Ionizante , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Dano ao DNA , Suplementos NutricionaisRESUMO
BACKGROUND CONTEXT: Low back pain with or without radicular leg pain is an extremely common health condition significantly impacting patient's activities and quality of life. When conservative management fails, epidural injections providing only temporary relief, are frequently utilized. Intradiscal oxygen-ozone may offer an alternative to epidural injections and further reduce the need for microdiscectomy. PURPOSE: To compare the non-inferiority treatment status and clinical outcomes of intradiscal oxygen-ozone with microdiscectomy in patients with refractory radicular leg pain due to single-level contained lumbar disc herniations. STUDY DESIGN / SETTING: Multicenter pilot prospective non-inferiority blocked randomized control trial conducted in three European hospital spine centers. PATIENT SAMPLE: Forty-nine patients (mean 40 years of age, 17 females/32 males) with a single-level contained lumbar disc herniation, radicular leg pain for more than six weeks, and resistant to medical management were randomized, 25 to intradiscal oxygen-ozone and 24 to microdiscectomy. 88% (43 of 49) received their assigned treatment and constituted the AS-Treated (AT) population. OUTCOME MEASURES: Primary outcome was overall 6-month improvement over baseline in leg pain. Other validated clinical outcomes, including back numerical rating pain scores (NRS), Roland Morris Disability Index (RMDI) and EQ-5D, were collected at baseline, 1 week, 1-, 3-, and 6-months. Procedural technical outcomes were recorded and adverse events were evaluated at all follow-up intervals. METHODS: Oxygen-ozone treatment performed as outpatient day surgeries, included a one-time intradiscal injection delivered at a concentration of 35±3 µg/cc of oxygen-ozone by a calibrated delivery system. Discectomies performed as open microdiscectomy inpatient surgeries, were without spinal instrumentation, and not as subtotal microdiscectomies. Primary analyses with a non-inferiority margin of -1.94-point difference in 6-month cumulative weighted mean leg pain NRS scores were conducted using As-Treated (AT) and Intent-to-Treat (ITT) populations. In post hoc analyses, differences between treatment groups in improvement over baseline were compared at each follow-up visit, using baseline leg pain as a covariate. RESULTS: In the primary analysis, the overall 6-month difference between treatment groups in leg pain improvement using the AT population was -0.31 (SE, 0.84) points in favor of microdiscectomy and using the ITT population, the difference was 0.32 (SE, 0.88) points in favor of oxygen-ozone. The difference between oxygen-ozone and microdiscectomy did not exceed the non-inferiority 95% confidence lower limit of treatment difference in either the AT (95% lower limit, -1.72) or ITT (95% lower limit, -1.13) populations. Both treatments resulted in rapid and statistically significant improvements over baseline in leg pain, back pain, RMDI, and EQ-5D that persisted in follow-up. Between group differences were not significant for any outcomes. During 6-month follow-up, 71% (17 of 24) of patients receiving oxygen-ozone, avoided microdiscectomy. The mean procedure time for oxygen-ozone was significantly faster than microdiscectomy by 58 minutes (p<.0010) and the mean discharge time from procedure was significantly shorter for the oxygen-ozone procedure (4.3±2.9 hours vs. 44.2±29.9 hours, p<.001). No major adverse events occurred in either treatment group. CONCLUSIONS: Intradiscal oxygen-ozone chemonucleolysis for single-level lumbar disc herniations unresponsive to medical management, met the non-inferiority criteria to microdiscectomy on 6-month mean leg pain improvement. Both treatment groups achieved similar rapid significant clinical improvements that persisted and overall, 71% undergoing intradiscal oxygen-ozone were able to avoid surgery.
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Quimiólise do Disco Intervertebral , Deslocamento do Disco Intervertebral , Dor Lombar , Ozônio , Radiculopatia , Adolescente , Dor nas Costas/cirurgia , Discotomia , Feminino , Humanos , Quimiólise do Disco Intervertebral/métodos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/tratamento farmacológico , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Masculino , Oxigênio/uso terapêutico , Ozônio/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Radiculopatia/cirurgia , Resultado do TratamentoRESUMO
Lung cancer has the highest mortality rate worldwide and is often diagnosed at late stages, requiring genotoxic chemotherapy with significant side effects. Cancer prevention has become a major focus, including the use of dietary and supplemental antioxidants. Thus, we investigated the ability of an antioxidant formulation (AOX1) to reduce DNA damage in human bronchial epithelial cells (BEAS-2B) with and without the combination of apple peel flavonoid fraction (AF4), or its major constituent quercetin (Q), or Q-3-O-d-glucoside (Q3G) in vitro. To model smoke-related genotoxicity, we used cigarette-smoke hydrocarbon 4-[(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc) as well as methotrexate (MTX) to induce DNA damage in BEAS-2B cells. DNA fragmentation, γ-H2AX immunofluorescence, and comet assays were used as indicators of DNA damage. Pre-exposure to AOX1 alone or in combination with AF4, Q, or Q3G before challenging with NNKOAc and MTX significantly reduced intracellular reactive oxygen species (ROS) levels and DNA damage in BEAS-2B cells. Although NNKOAc-induced DNA damage activated ATM-Rad3-related (ATR) and Chk1 kinase in BEAS-2B cells, pre-exposure of the cells with tested antioxidants prior to carcinogen challenge significantly reduced their activation and levels of γ-H2AX (p ≤ 0.05). Therefore, AOX1 alone or combined with flavonoids holds promise as a chemoprotectant by reducing ROS and DNA damage to attenuate activation of ATR kinase following carcinogen exposure.
RESUMO
Research into antibody-mediated disease, in response to immune dysfunction or to tumour development, has rapidly expanded in recent years. Antibodies binding to neuroreceptors can cause psychiatric features, including psychosis, in a minority of patients as well as neurological features. The responsiveness of some of these cases to immunotherapy supports the hypothesis that antibody-associated mechanisms play a role in the pathogenesis of psychotic diseases. The purpose of this chapter is to review autoantibodies that are most likely to be relevant for patients with psychotic symptoms. Herein, we describe receptor structure and mechanism of action, clinical and psychiatric features for the growing number of neuronal surface antibodies, including those to the N-methyl-D-aspartate (NMDA) receptor. The identification of a subgroup of patients with psychiatric features having antibody-mediated disease highlights the importance of considering the diagnosis, particularly in those patients presenting with a first episode of psychosis.
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Autoanticorpos , Transtornos Psicóticos , Humanos , Neurônios/imunologia , Transtornos Psicóticos/imunologia , Receptores de N-Metil-D-Aspartato/imunologiaAssuntos
Riso , Transtornos do Humor/diagnóstico , Doença de Parkinson/diagnóstico , Adulto , Antiparkinsonianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Diagnóstico Diferencial , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Hipocinesia/diagnóstico , Hipocinesia/tratamento farmacológico , Hipocinesia/metabolismo , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Cintilografia , Resultado do Tratamento , Tremor/diagnóstico , Tremor/tratamento farmacológico , Tremor/metabolismoRESUMO
PURPOSE: To determine statistically significant effects of oxygen/ozone treatment of herniated discs with respect to pain, function, and complication rate. MATERIALS AND METHODS: Random-effects metaanalyses were used to estimate outcomes for oxygen/ozone treatment of herniated discs. A literature search provided relevant studies that were weighted by a study quality score. Separate metaanalyses were performed for visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcome scales, as well as for complication rate. Institutional review board approval was not required for this retrospective analysis. RESULTS: Twelve studies were included in the metaanalyses. The inclusion/exclusion criteria, patient demographics, clinical trial rankings, treatment procedures, outcome measures, and complications are summarized. Metaanalyses were performed on the oxygen/ozone treatment results for almost 8,000 patients from multiple centers. The mean improvement was 3.9 for VAS and 25.7 for ODI. The likelihood of showing improvement on the modified MacNab scale was 79.7%. The means for the VAS and ODI outcomes are well above the minimum clinically important difference and the minimum (significant) detectable change. The likelihood of complications was 0.064%. CONCLUSIONS: Oxygen/ozone treatment of herniated discs is an effective and extremely safe procedure. The estimated improvement in pain and function is impressive in view of the broad inclusion criteria, which included patients ranging in age from 13 to 94 years with all types of disc herniations. Pain and function outcomes are similar to the outcomes for lumbar discs treated with surgical discectomy, but the complication rate is much lower (<0.1%) and the recovery time is significantly shorter.
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Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/epidemiologia , Dor Lombar/epidemiologia , Dor Lombar/prevenção & controle , Ozônio/uso terapêutico , Qualidade de Vida , Comorbidade , Humanos , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
Patients with recurrent head and neck cancer have poor quality of life and suffer dismally from debilitating symptoms. Ablative techniques offer patients an alternative, minimally invasive treatment option. As a palliative treatment, they improve quality of life with decreased pain, improved function and appearance. In addition, there is a reduction in tumor bulk and analgesia requirements. Advantages include a reduction in procedural cost, avoidance of complex repetitive surgeries, and an ability to visualize the treated area at the time of the procedure. Ablation therapies are an evolving and exciting treatment option in the head and neck, but a consensus on appropriate indications is currently unclear.
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Embolização Terapêutica/tendências , Neoplasias de Cabeça e Pescoço/terapia , Hipertermia Induzida/métodos , Hipertermia Induzida/tendências , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Radiologia Intervencionista/tendências , Cirurgia Assistida por Computador/tendências , Humanos , Cirurgia Assistida por Computador/métodosRESUMO
A 28-year-old man with long-standing right proptosis presented with an extensive multilobulated partially cystic orbital mass thought to be a lymphangioma. Because of concern that excision or debulking of the lesion was likely to be complicated by excessive bleeding, the lesion was injected with a mixture of ethiodized oil (Ethiodol) and cyanoacrylate glue under direct observation. The mixture caused the injected lobules to assume a firm, rubbery texture, allowing them to be excised without bleeding.