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1.
PLoS One ; 18(11): e0294033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37939150

RESUMO

Iron (Fe) is one of the limiting micronutrients essential for crop productivity. The goal of our study was to evaluate the effects of different sources and rates of Fe fertilization on the marketable yield, physical and chemical properties, and phytochemical quality of fresh market tomatoes (Solanum Lycopersicum L., cv. Sunbrite). A factorial experiment under a drip-irrigated plasticulture system was conducted in a completely randomized design with two sources of Fe (nano vs. chelated) and four rates of application (0, 10, 20, and 40 mg/L) with four replications. Results indicated that relative chlorophyll concentration in the leaf (SPAD index) increased significantly (by 24 to 27%) with 10 and 20 mg/L of both nano- and chelated Fe fertilization compared to the control. Increasing Fe fertilization decreased the leaf SPAD readings. The total fruit yield of tomato was 1.6 to 1.8 times higher under the chelated- and nano Fe fertilization and the increase in yield was significantly higher under the chelated Fe fertilization, when compared to the control. In contrast, the tomato harvest index was highest under 10 and 20 mg/L of nano Fe than under other Fe treatments. While the chelated Fe fertilized tomatoes had significantly higher concentrations of vitamin C (34%), ß-carotene (6%), total carotene (25%), flavonoid (17%), and polyphenol (66%), the nano Fe, in contrast, increased ß-carotene, total carotene, and polyphenol concentrations by 25, 33, 51, and 7%, respectively, compared to the control. The 20 mg/L chelated Fe significantly increased the vitamin C, total carotene, flavonoid, polyphenol concentration, and antioxidant capacity more than any other Fe treatments. Based on the principal components analyses, vitamin C, lycopene, and anthocyanin were identified as the core indicators of the tomato nutrition quality index (NQIndex). The NQIndex ranged from 47 to 54, falling within the medium level of nutritional quality (40 to <70). In conclusion, the chelated Fe, when applied at 20 mg/L, was the most appropriate rate based on highly correlated connectivity for the phytochemicals syntheses associated with the improved tomato antioxidant capacity.


Assuntos
Antioxidantes , Solanum lycopersicum , Antioxidantes/química , Carotenoides/análise , Ácido Ascórbico/análise , Frutas/química , Quelantes de Ferro , Ferro/análise , Flavonoides/análise , Polifenóis/análise
2.
Int Marit Health ; 72(3): 199-205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604990

RESUMO

BACKGROUND: Occupational noise exposure has been identified as a significant risk factor for fish harvesters. Chronic noise exposure causes hearing and other health problems and undermines the quality of life and well-being. This review paper aims to highlight noise-related auditory and non-auditory health effects among fish harvesters. MATERIALS AND METHODS: A systematic literature search approach was adopted using the following databases: PubMed, Embase, SCOPUS, Web of Science, Google Scholar, and by exploring grey literature. The literature search was conducted in 2020 (between October 15 and November 30). Relevant articles were explored by reviewing title, keywords, and abstract based on the inclusion and exclusion criteria. The full-text critical review of selected papers was made and finalized the most relevant studies. RESULTS: Initial 1,281 records were identified, exploring various databases and additional sources using relevant keywords. Duplicate articles were removed and retrieved 746 articles. After that, a screening of 746 research papers was done based on the selection criteria and finalised 28 articles for full-text review. Finally, articles were filtered based on the study's aim and extracted 17 papers for the final review. CONCLUSIONS: Noise-induced hearing loss was considered a significant health risk to fish harvesters across the studies, affecting physical and emotional well-being. The prevalence of hearing loss was observed from 6% to 80%. Other health problems, such as headache, dizziness, annoyance, stress, fatigue, elevated blood pressure, sleep disturbances, and impaired cognitive performance, were also reported. Further research is needed to validate the non-auditory health effects among fish harvesters.


Assuntos
Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Doenças Profissionais , Exposição Ocupacional , Animais , Pesqueiros , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Humanos , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/efeitos adversos , Ocupações , Qualidade de Vida
3.
Indian J Tuberc ; 68(1): 99-105, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33641859

RESUMO

Tuberculosis is a prime example of a social disease that requires social, economic and environmental interventions. However, research on social determinants of Multidrug-Resistant (MDR-TB) is limited. The five-stage scoping review showed the most common association of MDR-TB with multidimensional poverty (income, nutrition, education and social support) both as a contributing factor and a consequence of it. The review also found that physical environment (inadequate housing, overcrowding, poor physical environment, and smoking), health care needs, cultural determinants (race, ethnicity and gender), comorbidities had a strong influence on the development and transmission of MDR-TB. Since, epidemiology and care for MDR-TB are greatly influenced by socioeconomic factors, social, environmental and economic actions are needed in addition to the implementation of novel diagnostic techniques and treatments.


Assuntos
Projetos de Pesquisa , Determinantes Sociais da Saúde , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Saúde Global , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/etiologia
4.
Sci Total Environ ; 757: 143872, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33310568

RESUMO

Microplastics are an emerging global environmental contaminant that are affecting multiple spheres. Despite their ubiquity in all spheres of life and ecology, little is known about the health effects of microplastics exposure to humans. This scoping review explores the existing evidence on the potential human health effects of microplastics and subsequent knowledge gaps. An electronic search of published articles in PubMed, Scopus, EMBASE, Cochrane databases, and Google Scholar was conducted using a combination of subject headings and keywords relating to microplastics and human health effects. The initial search resulted in 17,043 published articles and grey literature documents. After a full review of published articles and their references, 129 publications were identified for further detailed review. These articles indicate that human exposure to microplastics can occur through ingestion, inhalation, and dermal contact due to their presence in food, water, air, and consumer products. Microplastics exposure can cause toxicity through oxidative stress, inflammatory lesions, and increased uptake or translocation. Several studies have demonstrated the potentiality of metabolic disturbances, neurotoxicity, and increased cancer risk in humans. Moreover, microplastics have been found to release their constituent compounds as well as those that are adsorbed onto their surface. Further research is needed to quantify the effects of microplastics on human health and their pathogenesis.


Assuntos
Microplásticos , Poluentes Químicos da Água , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Humanos , Plásticos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Syst Rev ; 9(1): 187, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807222

RESUMO

BACKGROUND: Recent surveys of Canadian cannabis users reflect increasing consumption rates, some of whom may have diabetes. However, healthcare providers have limited information resources on the effects of recreational cannabis in people with diabetes. This rapid review was commissioned by Diabetes Canada to synthesize available evidence to guide recommendations for care of people 13 years of age and older who live with diabetes. METHODS: PubMed, Embase and PsycINFO databases were searched from January 2008 to January 2019. Study selection, data abstraction and quality appraisal were completed by pairs of reviewers working independently and discrepancies were resolved by a third reviewer with pilot tests completed before each stage to ensure consistency. Data collected from included studies were tabulated and summarized descriptively. RESULTS: The search resulted in 1848 citations of which 59 publications were selected for screening, resulting in six observational studies (2 full-text articles and 4 conference abstracts) that met the pre-defined criteria for inclusion. Five studies reported higher glycated hemoglobin (HbA1c) in people with type 1 diabetes (T1D) who consumed recreational cannabis. In one study, students aged 17 to 25 years living with T1D self-reported poorer glycemic control and higher HbA1c when smoking cannabis. In one study of adults with T1D, cannabis use within the previous 12 months was associated with almost double the risk of diabetic ketoacidosis compared with no cannabis use (odds ratio [OR] 1.98; confidence interval [CI] [95% CI] 1.01-3.91). Risks for peripheral arterial occlusion and myocardial infarction were found to be higher in people with type 2 diabetes (T2D) who consumed recreational cannabis, and worse renal parameters were also reported in two separate studies of T1D and T2D. CONCLUSIONS: Recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviours in people with T1D. In people with T2D, recreational cannabis may increase risks for peripheral arterial occlusion, myocardial infarction and renal disease. However, the evidence base of this rapid review was limited to six observational studies of poor to fair methodological quality, and thus, further robust, higher quality research is required to confirm the potential impact of cannabis on diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122829.


Assuntos
Cannabis , Diabetes Mellitus Tipo 2 , Autogestão , Adulto , Glicemia , Canadá , Cannabis/efeitos adversos , Humanos
6.
J Clin Imaging Sci ; 9: 50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819827

RESUMO

Male patients presenting to the mammography department for workup of breast disease is an overall rare event compared to females. Gynecomastia is statistically the most common breast condition afflicting male patients, with ductal carcinoma an uncommon secondary diagnostic consideration. Secondary benign breast conditions or mimickers of breast disease in men are even rarer than primary carcinoma and can pose a significant challenge in breast imaging workups. We present a challenging workup of a superficial epidermoid cyst (EC) in a male patient with significant subcutaneous growth and indeterminate imaging characteristics, mimicking a breast neoplasm. Furthermore, we present undesirable consequences of performing a biopsy of an EC including rupture and abscess formation.

7.
JAMA Netw Open ; 2(11): e1916285, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774523

RESUMO

Importance: Diabetic retinopathy (DR) is the leading cause of low vision among working-age adults. An estimated 6.9 million people in Bangladesh were living with diabetes in 2017, which is projected to increase to more than 10 million people in 2025. Currently, no standardized and/or large-scale DR screening program exists in Bangladesh. Objective: To develop a novel fundus photograph-based eye screening model for early detection of DR to prevent vision loss in Bangladeshi individuals with diabetes. Design, Setting, and Participants: In this cross-sectional study, 49 264 patients with diabetes underwent opportunistic eye screening at 2 eye hospitals and 1 diabetic hospital in Bangladesh between June 1, 2010, and September 30, 2017. The data set was analyzed from April 8 to December 30, 2018. Technicians were trained to obtain 2-field digital fundus photographs and to grade each according to a standardized DR severity scale. Each patient was counseled and triaged for treatment using defined DR referral criteria. Main Outcomes and Measures: Primary DR grading outcomes, visual acuity, and treatment outcomes. Results: A total of 49 264 patients (54.3% male; mean [SD] age, 50.8 [12.3] years) underwent DR screening during a 7-year period. The DR prevalence rate across all 3 sites was 33% (95% CI, 33%-33%). Prevalence rates varied by center (Chittagong, 64.6% [95% CI, 64.0%-65.0%]; Dhaka, 39.8% [95% CI, 39.0%-41.0%]; and Feni, 13.0% [95% CI, 13.0%-14.0%]). Across all age groups, male patients were at higher risk of prevalent DR than female patients (odds ratio, 1.99; 95% CI, 1.90-2.07). The prevalence was 3.9% for preproliferative DR, 7.8% for proliferative DR, and 19.2% for maculopathy. Individuals with DR had significantly worse visual acuity than those with no DR (best-corrected visual acuity, 0.35 vs 0.21 logMAR; P < .001). The rate of moderate visual impairment was 12.2%, and the rate of blindness was 2.5%. Primary treatments included laser photocoagulation (n = 1637), intravitreal injection (n = 1440), and vitrectomy (n = 309). Conclusions and Relevance: Screening Bangladeshi individuals known to have diabetes using fundus photography identified large numbers of patients with sight-threatening proliferative DR, maculopathy, and visual impairment or blindness. Expansion of eye screening services in Bangladesh is warranted as part of a national government eye care and diabetes health policy.


Assuntos
Retinopatia Diabética/epidemiologia , Programas de Rastreamento/métodos , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh/epidemiologia , Criança , Estudos Transversais , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/prevenção & controle , Retinopatia Diabética/terapia , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
8.
Arthritis Rheumatol ; 70(12): 2003-2013, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29869839

RESUMO

OBJECTIVE: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3 CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3 CR1+CD59+ MNPs in modulating ILC3 function in AS patients. METHODS: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3 CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3 CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3 CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3 CR1+ monocytes was also performed. RESULTS: DcR-6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3 CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor-like molecule 1A (TL1A) and interleukin-23 (IL-23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3 CR1, were also expanded in the small intestines of treatment-naive SKG relative to BALB/c mice. The frequency of gut-derived CX3 CR1+CD59+CCR9+TL1A+IL-23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3 CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3 CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3 CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3. CONCLUSION: Proinflammatory CX3 CR1+CD59+TL1A+IL-23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.


Assuntos
Imunidade Inata , Linfócitos/imunologia , Monócitos/imunologia , Sistema Fagocitário Mononuclear/imunologia , Espondilite Anquilosante/imunologia , Adulto , Antígenos CD59/imunologia , Receptor 1 de Quimiocina CX3C/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-23/imunologia , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia
9.
Int J Med Microbiol ; 305(3): 392-403, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25804332

RESUMO

Helicobacter pylori from different individuals exhibits substantial genetic diversity. However, the kinetics of bacterial diversification after infection with a single strain is poorly understood. We investigated evolution of H. pylori following long-term infection in the primate stomach; Rhesus macaques were infected with H. pylori strain USU101 and then followed for 10 years. H. pylori was regularly cultured from biopsies, and single colony isolates were analyzed. At 1-year, DNA fingerprinting showed that all output isolates were identical to the input strain; however, at 5-years, different H. pylori fingerprints were observed. Microarray-based comparative genomic hybridization revealed that long term persistence of USU101 in the macaque stomach was associated with specific whole gene changes. Further detailed investigation showed that levels of the BabA protein were dramatically reduced within weeks of infection. The molecular mechanisms behind this reduction were shown to include phase variation and gene loss via intragenomic rearrangement, suggesting strong selective pressure against BabA expression in the macaque model. Notably, although there is apparently strong selective pressure against babA, babA is required for establishment of infection in this model as a strain in which babA was deleted was unable to colonize experimentally infected macaques.


Assuntos
Variação Genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Adesinas Bacterianas/genética , Animais , Biópsia , Hibridização Genômica Comparativa , Impressões Digitais de DNA , DNA Bacteriano/genética , Modelos Animais de Doenças , Rearranjo Gênico , Estudos Longitudinais , Macaca mulatta , Análise em Microsséries , Seleção Genética , Estômago/microbiologia
10.
Life Sci ; 111(1-2): 6-11, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24953608

RESUMO

AIMS: The aim was to study the differences in the effectiveness of two types of endothelin (ET) receptor antagonists (selective ET-A or dual ET-A/B antagonists) on the hearts of streptozotocin (STZ)-induced diabetic rats (type I diabetes) at functional and biochemical/molecular levels. MAIN METHODS: Citrate saline (vehicle) or STZ was injected into rats. The ET-A/B dual receptor antagonist (SB209670, 1mg/kg/day) and the ET-A receptor antagonist (TA-0201, 1mg/kg/day) were then administered to these rats. One week after injection, the animals were separated into those receiving SB209670, TA-0201 or vehicle by 4-week osmotic mini-pump. KEY FINDINGS: The VEGF level and percent fractional shortening in the diabetic heart were significantly decreased compared to the non-diabetic heart, whereas SB209670 and TA-0201 treatments greatly and comparably prevented this decrease. SB209670 treatment was more effective in reversing decreased expressions of KDR and phosphorylated AKT, downstream of VEGF angiogenic signaling, than TA-0201 treatment. The eNOS levels in hearts were significantly higher in diabetic rats than in healthy rats, and this increase was significantly reduced by TA-0210 but not by SB209670 treatment. SIGNIFICANCE: Improvement of KDR mRNA and pAKT levels by SB209670 but not TA-0201 suggests that dual ET-A/-B blockade may be effective in improving intracellular systems of these components in the diabetic rat heart. However, the present study also showed that TA-0201 or SB209670 improved percent fractional shortening and VEGF levels of the diabetic hearts to a similar extent, suggesting that ET-A blockade and dual ET-A/-B blockade are similarly effective in improving cardiac dysfunction in the diabetic rats.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Antagonistas do Receptor de Endotelina A , Antagonistas do Receptor de Endotelina B , Coração/efeitos dos fármacos , Indanos/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Animais , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Ecocardiografia , Coração/fisiopatologia , Ventrículos do Coração/química , Indanos/uso terapêutico , Insulina/sangue , Masculino , Óxido Nítrico Sintase Tipo III/análise , Pirimidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sulfonamidas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos
11.
Health Phys ; 106(6): 772-86, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24776912

RESUMO

Nuclear accidents or terrorist attacks could expose large numbers of people to ionizing radiation. Early biomarkers of radiation injury will be critical for triage, treatment, and follow-up of such individuals. The authors evaluated the utility of multiple blood biomarkers for early-response assessment of radiation exposure using a murine (CD2F1, males) total-body irradiation (TBI) model exposed to 6°Co γ rays (0.6 Gy min⁻¹) over a broad dose range (0-14 Gy) and timepoints (4 h-5 d). Results demonstrate: 1) dose-dependent changes in hematopoietic cytokines: Flt-3 ligand (Flt3L), interleukin 6 (IL-6), granulocyte colony stimulating factor (G-CSF), thrombopoietin (TPO), erythropoietin (EPO), and acute phase protein serum amyloid A (SAA); 2) dose-dependent changes in blood cell counts: lymphocytes, neutrophils, platelets, and ratio of neutrophils to lymphocytes; 3) protein results coupled with peripheral blood cell counts established very successful separation of groups irradiated to different doses; and 4) enhanced separation of dose was observed as the number of biomarkers increased. Results show that the dynamic changes in the levels of SAA, IL-6, G-CSF, and Flt3L reflect the time course and severity of acute radiation syndrome (ARS) and may function as prognostic indicators of ARS outcome. These results also demonstrate proof-in-concept that plasma proteins show promise as a complimentary approach to conventional biodosimetry for early assessment of radiation exposures and, coupled with peripheral blood cell counts, provide early diagnostic information to manage radiation casualty incidents effectively, closing a gap in capabilities to rapidly and effectively assess radiation exposure early, especially needed in case of a mass-casualty radiological incident.


Assuntos
Monitoramento de Radiação/métodos , Irradiação Corporal Total/efeitos adversos , Animais , Biomarcadores/sangue , Radioisótopos de Cobalto/efeitos adversos , Citocinas/sangue , Raios gama/efeitos adversos , Hematopoese/efeitos da radiação , Contagem de Linfócitos , Masculino , Camundongos , Neutrófilos/citologia , Neutrófilos/efeitos da radiação , Fatores de Tempo
12.
Life Sci ; 102(2): 127-33, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24641950

RESUMO

AIMS: Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. MAIN METHODS: Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. KEY FINDINGS: An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. SIGNIFICANCE: The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.


Assuntos
Modelos Animais de Doenças , Endotelina-1/biossíntese , Endotoxemia/metabolismo , Nefropatias/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptor PAR-2/antagonistas & inibidores , Receptor PAR-2/metabolismo , Animais , Endotelina-1/antagonistas & inibidores , Endotelina-1/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Masculino , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
13.
Radiat Meas ; 46(9): 877-881, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21949480

RESUMO

We previously used the γ-H2AX assay as a biodosimeter for total-body-irradiation (TBI) exposure (γ-rays) in a rhesus macaque (Macaca mulatta) model. Utilizing peripheral blood lymphocytes and plucked hairs, we obtained statistically significant γ-H2AX responses days after total-body exposure to 1-8.5 Gy ((60)Co γ-rays at 55 cGy min(-1)). Here, we introduce a partial-body exposure analysis method, Q(γ-H2AX), which is based on the number of γ-H2AX foci per damaged cells as evident by having one or more γ-H2AX foci per cell. Results from the rhesus monkey - TBI study were used to establish Q(γ-H2AX) dose-response calibration curves to assess acute partial-body exposures. γ-H2AX foci were detected in plucked hairs for several days after in vivo irradiation demonstrating this assay's utility for dose assessment in various body regions. The quantitation of γ-H2AX may provide a robust biodosimeter for analyzing partial body exposures to ionizing radiation in humans.

14.
PLoS One ; 5(11): e15544, 2010 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-21124906

RESUMO

BACKGROUND: There is a crucial shortage of methods capable of determining the extent of accidental exposures of human beings to ionizing radiation. However, knowledge of individual exposures is essential for early triage during radiological incidents to provide optimum possible life-sparing medical procedures to each person. METHODS AND FINDINGS: We evaluated immunocytofluorescence-based quantitation of γ-H2AX foci as a biodosimeter of total-body radiation exposure ((60)Co γ-rays) in a rhesus macaque (Macaca mulatta) model. Peripheral blood lymphocytes and plucked hairs were collected from 4 cohorts of macaques receiving total body irradiation doses ranging from 1 Gy to 8.5 Gy. Each cohort consisted of 6 experimental and 2 control animals. Numbers of residual γ-H2AX foci were proportional to initial irradiation doses and statistically significant responses were obtained until 1 day after 1 Gy, 4 days after 3.5 and 6.5 Gy, and 14 days after 8.5 Gy in lymphocytes and until 1 day after 1 Gy, at least 2 days after 3.5 and 6.5 Gy, and 9 days after 8.5 Gy in plucked hairs. CONCLUSION: These findings indicate that quantitation of γ-H2AX foci may make a robust biodosimeter for analyzing total-body exposure to ionizing radiation in humans. This tool would help clinicians prescribe appropriate types of medical intervention for optimal individual outcome. These results also demonstrate that the use of a high throughput γ-H2AX biodosimeter would be useful for days post-exposure in applications like large-scale radiological events or radiation therapy. In addition, this study validates a possibility to use plucked hair in future clinical trials investigating genotoxic effects of drugs and radiation treatments.


Assuntos
Cabelo/efeitos da radiação , Histonas/metabolismo , Linfócitos/efeitos da radiação , Irradiação Corporal Total , Adulto , Idoso , Animais , Relação Dose-Resposta à Radiação , Feminino , Raios gama , Cabelo/metabolismo , Humanos , Imuno-Histoquímica , Linfócitos/citologia , Linfócitos/metabolismo , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/diagnóstico , Lesões por Radiação/metabolismo , Radiometria/métodos
15.
Gastroenterology ; 137(4): 1367-79.e1-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19622359

RESUMO

BACKGROUND & AIMS: Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys. METHODS: Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; inoculation of a virulent H pylori strain alone (H); and ethyl-nitro-nitrosoguanidine in combination with H pylori (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies. RESULTS: Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsy specimens at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer. CONCLUSIONS: Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosamines found in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates.


Assuntos
Carcinógenos/toxicidade , Dieta/efeitos adversos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Metilnitronitrosoguanidina/análogos & derivados , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/microbiologia , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/microbiologia , Animais , Biópsia , Carcinoma in Situ/induzido quimicamente , Carcinoma in Situ/genética , Carcinoma in Situ/microbiologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Análise por Conglomerados , Reparo do DNA , Modelos Animais de Doenças , Progressão da Doença , Feminino , Gastrite/induzido quimicamente , Gastrite/genética , Gastrite/microbiologia , Gastroscopia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Macaca mulatta , Masculino , Metaplasia , Metilnitronitrosoguanidina/toxicidade , Análise de Sequência com Séries de Oligonucleotídeos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fatores de Tempo
16.
PLoS One ; 3(7): e2689, 2008 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-18648543

RESUMO

PCR detection of H. pylori in biological specimens is rendered difficult by the extensive polymorphism of H. pylori genes and the suppressed expression of some genes in many strains. The goal of the present study was to (1) define a domain of the 16S rRNA sequence that is both highly conserved among H. pylori strains and also specific to the species, and (2) to develop and validate specific and sensitive molecular methods for the detection of H. pylori. We used a combination of in silico and molecular approaches to achieve sensitive and specific detection of H. pylori in biologic media. We sequenced two isolates from patients living in different continents and demonstrated that a 546-bp domain of the H. pylori 16S rRNA sequence was conserved in those strains and in published sequences. Within this conserved sequence, we defined a 229-bp domain that is 100% homologous in most H. pylori strains available in GenBank and also is specific for H. pylori. This sub-domain was then used to design (1) a set of high quality RT-PCR primers and probe that encompassed a 76-bp sequence and included at least two mismatches with other Helicobacter sp. 16S rRNA; and (2) in situ hybridization antisense probes. The sensitivity and specificity of the approaches were then demonstrated by using gastric biopsy specimens from patients and rhesus monkeys. This H. pylori-specific region of the 16S rRNA sequence is highly conserved among most H. pylori strains and allows specific detection, identification, and quantification of this bacterium in biological specimens.


Assuntos
Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Animais , Sequência de Bases , Biópsia , Clonagem Molecular , Sequência Conservada , Primers do DNA/química , Gastrite/microbiologia , Hibridização In Situ , Macaca mulatta , Dados de Sequência Molecular , RNA Ribossômico 16S/química , Análise de Sequência de DNA , Estômago/microbiologia , Estômago/patologia
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