RESUMO
The Food and Drug Administration (FDA) can regulate the introduction of new tobacco products and some changes to existing products. Cigarette packs have been used as a marketing tool to target specific groups and priority populations. Research has shown that sexual and gender minority (SGM) adults are substantially more likely to use tobacco products than their straight and cisgender counterparts. However, research to inform the FDA's regulatory decisions regarding cigarette packs targeting priority populations is nascent. To fill this gap, we conducted an online experiment in 2018, randomizing U.S. adults who reported current smoking (N = 954, 52% were SGM) to view one of three cigarette packs. A graphic designer developed "Glacier" branded packs with three levels of SGM imagery: (1) no targeting, (2) subtle targeting, and (3) a rainbow "pride edition." Participants viewed and rated the pack using cognitive, affective, and behavioral measures informed by theory. We used a linear model framework to compare the two SGM-targeted packs with the not targeted version and tested interactions between pack and SGM identity for the dependent variables. We stratified results by SGM status. SGM status was a significant moderator of the relationship between the pack and ratings of appeal, positive affect, feeling shocked, and intent to try with a coupon. Findings from this study revealed that packs designed for SGM populations can disproportionately change cognitive, affective, and behavioral intention responses for SGM smokers. Products entering the market should be assessed by FDA for the appeal of their packs to vulnerable populations.
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Sistemas Eletrônicos de Liberação de Nicotina/economia , Marketing/métodos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Produtos do Tabaco/economia , Vaping/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Grupos Minoritários/estatística & dados numéricos , Medição de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Pessoas Transgênero , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Globally, the tobacco industry is promoting heated tobacco products. These products may represent a strategy to promote dual use of tobacco products. One product, IQOS from Philip Morris International, is being proposed in the USA for marketing as a less harmful product. The visual design of tobacco products can influence consumers by implying product characteristics. Thus, we sought to test the impact of IQOS packaging designs on cognitive, affective and behavioural intention responses. METHODS: From existing IQOS packages used globally, we developed three IQOS packages that decreasingly linked the product to the Marlboro brand. In September to October 2018, we assigned participants randomly to one package in an online experiment. All participants (n=954) were US adults reporting current smoking and no colour blindness. The experiment used quota sampling to ensure diversity by gender, sexual orientation, race, ethnicity and education. Measures were informed by the Context of Consumption Framework. To assess differences in ratings, we conducted non-parametric Kruskal-Wallis tests with post hoc comparisons using Dunn's test. RESULTS: We found significant differences in cognitive indicators including appeal (H=6.87, p=0.03), uniqueness (H=15.68, p<0.01), brand equity-quality (H=122.35, p<0.01) and perceived safety compared with other tobacco products (H=14.27, p<0.01). Participants rated packages similarly on affective and behavioural intention measures. All were rated low for talking to others about the product and high for interest in trying with a coupon. CONCLUSION: Linking or separating IQOS products with a well-established cigarette brand changes how adult smokers respond to the product. Regulators should consider the visual design of packaging.
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Afeto , Cognição , Intenção , Embalagem de Produtos/métodos , Fumantes/psicologia , Produtos do Tabaco , Adulto , Feminino , Humanos , Masculino , Distribuição AleatóriaRESUMO
BACKGROUND AND AIM: Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population. METHODS: Fifty (29 ± 7 yr) men (n = 19) and women (n = 31) classified as overweight (26.4 ± 1.8 kg/m2) participated in this observational study. Blood pressure and blood metabolites were measured after an overnight fast. Lactate was also measured before and after a three-day eucaloric high-fat (70 %) diet. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Visceral adipose tissue mass was determined via dual X-ray absorptiometry. RESULTS: Triglycerides (r = 0.55, p=<0.0001), HOMA-IR (r = 0.53, p=<0.0001), and systolic and diastolic (both, r = 0.36, p = 0.01) blood pressures associated with fasting plasma lactate. No differences in visceral adipose tissue existed between the sexes (p = 0.41); however, the relationship between visceral adipose tissue and lactate existed only in females (r = 0.59, p = 0.02) but not in males (p = 0.53). Fasting lactate and HOMA-IR increased in males (p = 0.01 and p = 0.02, respectively), but not females, following a three-day high-fat diet. CONCLUSION: Indices of the metabolic syndrome associated with fasting plasma lactates in young relatively healthy individuals. Fasting lactate also increased in a sex-specific manner after a three-day high fat diet. Thus, lactate could become a clinical marker for metabolic disease risk.
Assuntos
Resistência à Insulina , Síndrome Metabólica , Feminino , Humanos , Masculino , Biomarcadores , Jejum , Insulina , Ácido Láctico , Obesidade/complicações , Adulto Jovem , AdultoRESUMO
INTRODUCTION: While plain packaging of tobacco products has emerged as a policy intervention to reduce smoking, regulators in the US have limited ability to implement plain packaging. We sought to identify the impact of subtle changes to cigarette packaging (Study 1) and how packaging design influenced participant choices based on appeal, harm, and style (Study 2). METHODS: We conducted two discrete-choice experiments with US adult smokers online in 2018. In Study 1 (n=285), we assessed participants' selections based on subtle changes to pack design features (dimensions, color saturation, logo size). In Study 2 (n=284), we assessed three choices in which participants selected packs based on appeal, harmfulness, and best match to their personal style. Study 2 packs varied by color hue, design with different levels of organic labeling and natural imagery, and color saturation. RESULTS: Pack designs influenced smokers' choices. In Study 1, pack dimensions and color saturation emerged as the most important features, and, in Study 2, design and color hue were the most influential characteristics. CONCLUSIONS: Regulators should consider how the design of cigarette packages may influence consumers' perceptions and choices.
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BACKGROUND: This prospective multicenter sentinel lymph node (SLN) trial investigated whether molecular analysis would improve the detection of SLN metastases and their prognostic value. We report mammaglobin quantitative real-time polymerase chain reaction (qRT-PCR) results and clinical outcome for 547 patients (mean follow-up 7 years). METHODS: Breast cancer patients (excluding stage IV disease or palpable nodes) were enrolled from 1996 to 2005 at 16 institutional review board-approved sites. Alternate 2-mm serial sections of each SLN were examined by hematoxylin and eosin staining with or without immunohistochemistry at multiple levels or blinded and assayed by Taqman qRT-PCR according to previously established thresholds. RESULTS: Mammaglobin remains a highly specific (99%), sensitive (97% primary tumor; 82% N1 SLN) marker for breast cancer. Mammaglobin SLN expression was associated with other prognostic factors, was detected in most patients with distant recurrence (48 of 79; 61%), and was associated with decreased recurrence-free survival (log rank P < 0.0001). Molecular analysis upstaged 13% (52 of 394) node-negative (N0) patients who exhibited a significantly lower distant recurrence-free survival compared to node-negative, PCR-negative patients (80 vs. 91%; P < 0.04). N0 patients with PCR-positive SLN were 3.4 times more likely to experience relapse than PCR-negative patients (odds ratio 3.4; 95% confidence interval 1.6-7.1; P = 0.001). However, molecular staging failed to predict most of the N0 patient recurrences (25 of 34) and was not a statistically significant independent predictor of distant recurrence. CONCLUSIONS: To our knowledge, these data are the first to prospectively compare PCR detection of SLN metastases with long-term outcome in breast cancer patients. Molecular staging of SLN detected clinically significant disease missed by standard pathology. Further refinement and optimization of molecular staging is indicated to improve clinical utility.
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Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Lobular/diagnóstico , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/diagnóstico , Biópsia de Linfonodo Sentinela , Uteroglobina/genética , Axila , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Mamoglobina A , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Uteroglobina/metabolismoRESUMO
We recently established that the SOD1-G93A transgenic mouse is a suitable model for oral-stage dysphagia in amyotrophic lateral sclerosis (ALS). The purpose of the present study was to determine whether it could serve as a model for pharyngeal-stage dysphagia as well. Electrophysiological and histological experiments were conducted on end-stage SOD1-G93A transgenic mice (n = 9) and age-matched wild-type (WT) littermates (n = 12). Transgenic mice required a twofold higher stimulus frequency (40 Hz) applied to the superior laryngeal nerve (SLN) to evoke swallowing compared with WT controls (20 Hz); transgenic females required a significantly higher (P < 0.05) stimulus frequency applied to the SLN to evoke swallowing compared with transgenic males. Thus, both sexes demonstrated electrophysiological evidence of pharyngeal dysphagia but symptoms were more severe for females. Histological evidence of neurodegeneration (vacuoles) was identified throughout representative motor (nucleus ambiguus) and sensory (nucleus tractus solitarius) components of the pharyngeal stage of swallowing, suggesting that pharyngeal dysphagia in ALS may be attributed to both motor and sensory pathologies. Moreover, the results of this investigation suggest that sensory stimulation approaches may facilitate swallowing function in ALS.
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Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/etiologia , Faringe/patologia , Análise de Variância , Animais , Transtornos de Deglutição/patologia , Modelos Animais de Doenças , Eletromiografia , Feminino , Humanos , Masculino , Camundongos , Superóxido Dismutase/genéticaRESUMO
Relatively little is known about the underlying neuropathology of dysphagia in amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive. Tremendous progress toward understanding and treating dysphagia in ALS may be possible through the use of an animal model of dysphagia in ALS research; however, no such animal model currently exists. The most logical candidate to consider is the SOD1-G93A transgenic mouse, the most widely investigated animal model of ALS. To investigate whether this animal model develops dysphagia, oral behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were evaluated at three time points based on hind limb motor function: asymptomatic (60 days), disease onset (approximately 110 days), and disease end-stage (approximately 140 days). Age-matched nontransgenic littermates (n = 30) served as controls. At each time point, lick and mastication rates were significantly lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal and hypoglossal nuclei, two key motor components involved in mastication and licking behaviors. These results demonstrate a clinicopathologic correlation of oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A transgenic mouse as a bona fide animal model of oral dysphagia in ALS.
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Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/etiologia , Mastigação , Animais , Índice de Massa Corporal , Progressão da Doença , Comportamento Alimentar , Camundongos , Modelos Animais , Superóxido DismutaseRESUMO
To explore the radioprotective effect of a standardized North American ginseng extract (NAGE) on human peripheral blood lymphocytes (PBL), a micronuclei (MN) assay was conducted in PBL obtained from 12 volunteers. NAGE (50-1000 microg/mL) and WR-1065 (1 mM and 3 mM) were applied to PBL cultures at 0 h and 90 min post-irradiation. It was found that (1) the baseline MN yield of PBL ranged from 14.4 +/- 1.5 to 15.9 +/- 1.5 per 1000 binucleated cells (p > 0.05); after irradiation (1 Gy and 2 Gy), the MN yield increased sharply; (2) MN yields declined with increasing concentrations of NAGE and WR-1065. Even at 90 min post-irradiation of 1 Gy, the maximum level of MN reduction rate caused by NAGE and WR-1065 was 53.8% and 59.2%, respectively; after 2 Gy irradiation, it was 37.3% and 42%, respectively; (3) the MN distribution in PBL followed a non-Poisson distribution in all cases; and (4) both NAGE and WR-1065 showed no significant effect on the proliferation index of lymphocytes. The results indicate that NAGE is a relatively non-toxic natural product, which can be administered as a dietary supplement and has the potential to be a radiation countermeasure.
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Linfócitos/efeitos dos fármacos , Mercaptoetilaminas/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Protetores contra Radiação/farmacologia , Adulto , Células Cultivadas , Césio/toxicidade , Cloretos/toxicidade , Relação Dose-Resposta a Droga , Ginsenosídeos/farmacologia , Humanos , Linfócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Testes para Micronúcleos , Pessoa de Meia-Idade , Radiação IonizanteRESUMO
BACKGROUND: This study sought to better define the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in treating prostate cancer. MATERIALS AND METHODS: Subjects selected (n = 37) were stage I-II prostate cancer patients meeting the eligibility requirements for RTOG protocols 94-08 or 94-13. Flow cytometric monitoring of circulating T helper (Th), T suppressor/cytotoxic (Ts), natural killer (NK) and B lymphocytes was performed weekly. RESULTS: Significant reduction of all lymphocyte subsets occurred as a result of xRT. Comparison between treatment groups demonstrated that the B lymphocyte and NK lymphocyte radioresponse was not influenced by TAS, but the Th and Ts lymphocyte response was, with addition of TAS leading to less radiation-induced decline. CONCLUSION: The basis for this T cell response is unclear, but may involve a TAS-induced reduction of testosterone's immunomodulation of T cell proliferation and apoptosis and/or a direct, TAS-induced thymic stimulation. Our data suggest that addition of TAS to xRT appears to have no detrimental effects on lymphocyte subsets, and, indeed, may have favorable effects on T cells.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Linfócitos T/imunologia , Idoso , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Flutamida/administração & dosagem , Gosserrelina/administração & dosagem , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Linfócitos T/efeitos dos fármacos , Linfócitos T/efeitos da radiaçãoRESUMO
BACKGROUND: An increased lung to heart ratio (LHR) on thallium-201 (Tl-201) stress myocardial perfusion imaging (MPI) is a predictor of adverse cardiac events and identifies people with extensive coronary artery disease (CAD). The implications of increased LHR in patients undergoing stress technetium-99m (tc-99m) sestamibi are developing. Our aim is to evaluate the relationship between increased LHR and extent of CAD in patients undergoing tc-99m sestamibi MPI. METHODS: We reviewed the records and images of 530 consecutive subjects who underwent exercise or adenosine tc-99 m sestamibi MPI. One hundred thirty-two had transient or partially reversible myocardial perfusion defects and 79 (exercise=34, adenosine=45, male=43, female=36, mean age=61 years) of these underwent coronary angiography (study population). The average LHR of these 79 subjects was compared to 79 patients (control population) with normal scans (exercise=50, adenosine=29, male=34, female=45, mean age=60 years). RESULTS: The mean LHR (+/-SE) in subjects with normal scans was 0.30+/-0.01. The mean LHR for those with abnormal scans and single vessel CAD who underwent exercise was 0.32+/-0.01 and pharmacological stress was 0.31+/-0.01. There was no statistically significant difference between the LHR of those with a normal scan and those with single vessel disease and an abnormal scan. However, there was a statistically significant association between the elevated LHR and multi-vessel CAD. The mean LHR for subjects with multi-vessel CAD with exercise was 0.39+/-0.01 (p=0.000) and for adenosine was 0.39+/-0.02 (p=0.000). CONCLUSION: An elevated LHR in patients undergoing exercise or pharmacological tc-99m MPI correlates with multi-vessel CAD.
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Doença da Artéria Coronariana/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio Tc 99m Sestamibi/farmacocinética , Adenosina , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária/fisiologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Estudos Retrospectivos , Índice de Gravidade de Doença , VasodilatadoresRESUMO
PURPOSE: To test the hypothesis that, before treatment, prostate cancer patients who demonstrate a high yield of ex vivo radiation-induced micronucleus (MN) in G(0) lymphocytes represent a patient population with a greater-than-average risk of developing radiotherapy (RT)-related morbidity. METHODS AND MATERIALS: We prospectively conducted the cytokinesis-block MN assay of peripheral blood lymphocytes (PBLs) in 38 prostate cancer patients. Before the initiation of RT, PBLs from each patient were irradiated (1-4 Gy). The mean patient age +/- SEM was 68.7 +/- 1.0 years. The clinical stage was T1 in 17, T2 in 15, and T3 in 6. The preoperative prostate-specific antigen level was < or =4 ng/mL in 5, 4-10 ng/mL in 18, and >10 ng/mL in 15. All patients underwent standardized pelvic external beam radiotherapy (range 41.4-50.4 Gy) and boost (range 16-26 Gy). The mean follow-up +/- SEM was 32.8 +/- 4.6 months. At the end of follow-up, a radiation oncologist scored the GI or GU morbidity according to the Radiation Therapy Oncology Group criteria without knowledge of the MN data. RESULTS: We found that between the average reactors (n = 25; i.e., patients who had Grade 1 or less RT-related morbidity) and over reactors (n = 13; i.e., patients who developed Grade 2 or greater RT-related morbidity), the differences in the ex vivo radiation dose-response relationship of MN yield in PBLs were highly significant, especially at doses of > or =2 Gy. Also, the development of RT-related morbidity correlated with the radiation dose-response relationship of MN yield in PBLs before treatment, but did not correlate with any of the patients' clinical variables. CONCLUSION: Our findings suggest that the pre-RT ex vivo radiation dose-response relationship of MN yield in PBLs may be a significant predictive factor for the development of GI or GU morbidity in prostate cancer patients after pelvic RT.
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Gastroenteropatias/etiologia , Linfócitos/efeitos da radiação , Doenças Urogenitais Masculinas/etiologia , Neoplasias da Próstata/radioterapia , Radioterapia/efeitos adversos , Idoso , Relação Dose-Resposta à Radiação , Humanos , Linfócitos/sangue , Linfócitos/patologia , Masculino , Morbidade , Pelve/efeitos da radiação , Tolerância a Radiação , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Estados UnidosRESUMO
To verify the applicability of the micronucleus (MN) yield in peripheral blood lymphocytes (PBLs) as a quantitative biodosimeter for monitoring in vivo ionizing radiation damage, we applied the cytokinesis-blocked micronucleus assay in PBLs of cancer patients treated with partial-body radiotherapy. Dosimetric information on these 13 patients represented a wide range in the number of fractions, cumulative tumor dose, total integral dose, and equivalent total-body absorbed dose. We found in PBLs of these patients that (1) the MN yield increased linearly with the equivalent total-body absorbed dose (r = 0.8, P = 0.002), (2) the distributions of the MN yields deviated significantly from Poisson, and (3) there was a general decline in MN yields with increasing length of follow-up, but with considerable variation between individuals. The average rate of decline was found to be linear and was correlated with the equivalent total-body absorbed dose (r = 0.7, P = 0.007). Further, at 19-75 months of follow-up time, seven patients showed higher MN yields than their respective levels before radiotherapy, indicating the persistence of radiation-induced residual cytogenetic damage. Our findings suggest that the MN yield in human PBLs offers a reliable acute and perhaps chronic biodosimeter for in vivo radiation dose estimation. After the completion of radiotherapy, the persistence of elevated MN yield in PBLs is a reflection of the surviving population of radiation-induced genetically aberrant cells.
Assuntos
Linfócitos/patologia , Linfócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Radioterapia/efeitos adversos , Idoso , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Masculino , Micronúcleos com Defeito Cromossômico/patologia , Pessoa de Meia-Idade , Fatores de TempoRESUMO
To assess the effect of Chinese ginseng in modifying the radiation-induced micronuclei (MN) yield in human G(o) peripheral blood lymphocytes (PBL), we conducted the cytokinesis-blocked (CB) MN assay in blood samples obtained from healthy volunteers (n=4). Before (137)Cs ex vivo irradiation, mononuclear cell cultures from each sample were incubated 24 h with different concentrations (0-2000 microg ml(-1)) of crude water extract of ginseng dry root. We found that (1) at 0 Gy and without the presence of ginseng, MN yield (mean+/-S.E.M.) was 11.7+/-2.7 per 1000 binucleated (BN) cells. Different concentrations of ginseng crude water extract did not affect the MN yields and the proliferative activity of PBL; (2) after 1 and 2 Gy exposure, radiation alone sharply increased the MN yields, respectively, to 119.6+/-17.4 and 340.5+/-20.9 per 1000 BN cells. However, treatment with ginseng for 24 h before radiation exposure, resulted in a significant linear decline of MN yields as ginseng concentration increases. Compared to radiation alone, the extent to which ginseng water extract reduced the MN yields induced by 1 Gy exposure was 46.0% at 1500 microg ml(-1) and 61.5% at 2000 microg ml(-1), and with 2 Gy exposure, it was 38.6% at 1500 microg ml(-1) and 46.5% at 2000 microg ml(-1); (3) MN data suggested a tendency for overdispersion relative to the Poisson model; and (4) over the different levels of ginseng concentrations, the trend in micronucleated BN index was as similar as that of the MN yields. These results indicated that (1) ginseng crude water extract exerts no apparent cytogentic effect on human PBL at concentrations up to 2000 microg ml(-1) as evaluated by the CBMN assay; and (2) the protection of ginseng water extract against (137)Cs-induced MN in human PBL is concentration-dependence. Therefore, our findings indicated that ginseng may have therapeutic value as a possible radioprotector for normal tissue during radiotherapy of cancer patients.
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Linfócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Panax , Protetores contra Radiação/farmacologia , Adulto , Idoso , Relação Dose-Resposta a Droga , Humanos , Ativação Linfocitária/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/ultraestrutura , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Pessoa de Meia-Idade , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Ionizing radiation (IR) initiates intracellular oxidative stress through enhanced formation of reactive oxygen species (ROS) that attack DNA leading to cell death. Because of the diversity of IR applied in medicine, agriculture, industry, and the growing threats of global terrorism, the acquisition of radioprotectors is an urgent need for the nation. However, the applicability of radioprotectors currently under investigation is limited due to their inherent toxicity. OBJECTIVE: This study investigated the effect of a standardized North American ginseng extract (NAGE, total ginsenoside content: 11.7%) on DNA damage in human lymphocytes at 90 minutes postirradiation. DESIGN: With the application of NAGE (250-1000 microg mL(-1)) at 90 minutes postirradiation (1 and 2 Gy), DNA damage in lymphocytes obtained from 40 healthy individuals was evaluated by cytokinesis-block micronucleus assay. Similar experiments were also performed in lymphocytes treated with WR-1065 (1 mmol/L or 3 mmol/L). In addition, before and after irradiation, lymphocytes obtained from 10 individuals were measured for their total antioxidant capacity (TAC) and the reactive oxygen species (ROS). RESULTS: The significant effect of NAGE against (137)Cs-induced micronuclei (MN) in lymphocytes is concentration dependent. NAGE (750 microg mL(-1)) reduced MN yield by 50.7% after 1 Gy and 35.9% after 2 Gy exposures, respectively; these results were comparable to that of WR-1065. Furthermore, we also found that NAGE reduces MN yield and ROS but increases TAC in lymphocytes. CONCLUSIONS: Our results suggest that NAGE is a relatively nontoxic natural compound that holds radioprotective potential in human lymphocytes even when applied at 90 minutes postirradiation. One of the radioprotective mechanisms may be mediated through the scavenging of free radicals and enhancement of the intracellular TAC.
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Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Lesões por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Adulto , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Dano ao DNA , Feminino , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Linfócitos/efeitos da radiação , Masculino , Mercaptoetilaminas/farmacologia , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Lesões por Radiação/genética , Radiação Ionizante , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Método Simples-CegoRESUMO
The multifold bioactive medicinal properties of ginseng have been closely linked to its antioxidative ability, which is related to its ginsenoside content. Since the key mechanism of radiation-induced cell death and tissue damage is the generation of reactive oxygen species (ROS) that attack cellular DNA, this study focuses on the impact of a standardized North American ginseng extract (NAGE) on (137)Cs-induced oxidative stress in human peripheral lymphocytes (PBL) obtained from 10 healthy individuals (6M/4F), 42.7 +/- 4.6 years of age. At two different time points (0 h and 24 h before irradiation), we applied NAGE (250 - 1000 microg ml(-1)) to mononuclear cell cultures for cytokinesis-block micronuclei (MN) assay and determination of the state of oxidative stress in PBL. We found that at both time points, NAGE significantly reduced the MN yields in PBL after irradiation (1 and 2 Gy) in a concentration-dependent manner (P<0.001). Compared with radiation alone, the maximum reduction rate of MN yield were 51.1% and 49.1% after 1 Gy and 2 Gy exposures, respectively. We also found that before irradiation the presence of NAGE in the culture medium resulted in a significant increased intracellular total antioxidant capacity (TAC) in PBL. At both time points, the increment of (137)Cs-induced MN yields in PBL was positively correlated with the increment of intracellular ROS production (R = 0.6 - 0.7, P = 0.002), but negatively correlated with the reduction of TAC levels (R = -0.4 -0.5, P = 0.02 - 0.004). However, the presence of NAGE in the culture medium significantly increased the TAC levels, while concomitantly decreasing both ROS production and MN yields in PBL (P<0.001). Our findings that NAGE is effective in protecting human PBL against radiation-induced oxidative stress should encourage further in vivo study of dietary supplementation with NAGE as an effective natural radiation countermeasure.
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A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.