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1.
J Clin Immunol ; 43(8): 1891-1902, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37526892

RESUMEN

Living organisms are exposed to exogenous and endogenous agents that affect genomic integrity by creating DNA double strand breaks (DSBs). These breaks are repaired by DNA repair proteins to maintain homeostasis. Defects in DNA repair pathways also affect lymphocyte development and maturation, as DSB sites are critical intermediates for rearrangements required for V(D)J recombination. Recent classifications for inborn errors of immunity (IEIs) have listed DNA repair defect genes in a separate group, which suggests the importance of these genes for adaptive and innate immunity. We report an interesting case of a young female (index P1) with mutations in two different genes, DCLRE1C and FANCA, involved in DNA repair pathways. She presented with clinical manifestations attributed to both defects. With the advent of NGS, more than one defect is increasingly identified in patients with IEIs. Familial segregation studies and appropriate functional assays help ascertain the pathogenicity of these mutations and provide appropriate management and genetic counseling.


Asunto(s)
Bioensayo , Anemia de Fanconi , Humanos , Femenino , Genómica , Homeostasis , Inmunidad Innata
2.
Radiat Environ Biophys ; 56(3): 227-239, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28612110

RESUMEN

To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells. Considerably higher glucose uptake in both cancer cells lines was observed indicating higher rates of glycolysis. IA significantly inhibited glycolysis as reflected by GAPDH activity inhibition. Radiomodifying effects of IA were found to be concentration dependent in both cancerous and non-cancerous cells. The response in non-cancerous was found to be biphasic: at lower concentrations, it offered significant radioprotection; however, the protection decreased with increasing concentration. Moreover, at the highest tested concentration, marginal radiosensitization was also observed (as indicated by clonogenic assay). In both cancer cells, IA offered significant amount of radiosensitization which was considerably high at higher concentrations. Further experiments were carried out to estimate the Dose Modification Factor (DMF) to quantify and compare relative radiosensitization by IA in cancer and normal cell lines. The DMF was calculated for three different concentrations of IA, 0.5, 1, and 1.5 µg/ml, and corresponding values were found to be 1.26, 1.43, and 1.89 for A549 cancer cells, whereas for normal CHO cells, it was 1.13, 1.13, and 1.24. In conclusion, differential killing and radiosensitizing effects of IA suggest that it may have potential use as a anticancer agent and radiosensitizer in cancer therapy.


Asunto(s)
Yodoacetatos/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/efectos de la radiación , Células CHO , Muerte Celular/efectos de los fármacos , Muerte Celular/efectos de la radiación , Línea Celular Tumoral , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Glucosa/metabolismo , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/efectos de la radiación
3.
Natl Med J India ; 29(3): 163-165, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27808069

RESUMEN

Public-private partnerships are being encouraged as a part of the comprehensive development framework. We assessed the work profiles of registered non-governmental organizations (NGO) working on health-related activities in Udaipur district, Rajasthan, India by conducting a 16-item pretested questionnaire study. The questions related to various facets of their activities, their scope and process of evaluation. Of the 66 NGOs selected, most (28 [42%]) were working among the general population and had a partnership with a public entity (43 [65.1%]). The running capital of most NGOs (27 [41%]) was `100 000-2 000 000. Only 25 (38%) had a monitoring system to evaluate their progress. There are immense opportunities for NGOs in the health sector in Udaipur. The need of the hour is to encourage various public and private institutions to work together to achieve excellence in healthcare and service delivery.


Asunto(s)
Atención a la Salud , Asociación entre el Sector Público-Privado , Encuestas y Cuestionarios , Atención a la Salud/organización & administración , Atención a la Salud/estadística & datos numéricos , Humanos , India , Asociación entre el Sector Público-Privado/organización & administración , Asociación entre el Sector Público-Privado/estadística & datos numéricos
4.
Niger Postgrad Med J ; 23(4): 227-231, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28000645

RESUMEN

BACKGROUND: The community-based dental outreach programs play a very crucial role in declining discovery-delivery disconnect by introducing awareness through health education and dental adumbrating services to the community members. However, the success of any oral health programme depends largely on how it meets the needs and expectations of the target community. Therefore, the present study was designed for the assessment of patient satisfaction at various rural outreach dental camps conducted over a period of 2 months. MATERIALS AND METHODS: The present study was conducted on patients visiting weekly and monthly outreach dental programmes organised by the Department of Public Health Dentistry. Data were obtained from a total of 298 patients using a pre-tested questionnaire as a survey instrument. The questionnaire consisted of nine questions, measuring the patient satisfaction levels on a five-point Likert scale. RESULTS: The highest mean satisfaction score (4.97 ± 0.59) was observed for the question on the overall performance of camp, whereas waiting time for treatment, quality of the treatment and explanation of need for referral exhibited lowest mean scores. The mean satisfaction scores for the monthly camp (4.55 ± 0.52) were significantly higher as compared to the weekly camps (4.38 ± 0.55) (P = 0.013). CONCLUSION: The results of the study showed that the patient satisfaction scores were satisfactory to good for various aspects of the weekly and monthly dental outreach programmes. Such programmes should be conducted on regular basis, and comprehensive oral care should be provided.


Asunto(s)
Atención Odontológica , Satisfacción del Paciente , Humanos , India , Nigeria , Satisfacción Personal , Población Rural , Encuestas y Cuestionarios
6.
Life (Basel) ; 14(5)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38792626

RESUMEN

The aim of this study was to conduct salivary, microbiological, and caries risk assessments in relation to caries experience among individuals with intellectual disability in an institutional center in the Al-Baha region, Saudi Arabia. A cross-sectional study was conducted among 89 patients residing in special care homes in the Al-Baha region, Saudi Arabia, from October 2023 to February 2024. The demographic details of all participants were recorded. Clinical oral examinations were performed for the decayed, missing, or filled teeth (DMFT) and plaque indices. Salivary and microbiological assessments were also carried out. The mean age of the study sample was 30.11 ± 4.39 years, and the mean duration of years spent residing in the facility was 26.49 ± 4.66. There was no significant difference observed across plaque scores, S. mutans colony count, salivary rate, pH, DFMT, and caries experience when they were compared across the levels of severity of intellectual disability. Statistically significant differences were observed across diet score, circumstance score, and chances to avoid caries and were found to be correlated with the severity of intellectual disability (p = 0.001, p = 0.001, and p = 0.002), respectively. The cariogram revealed that participants in this study had poor oral health status, with participants with severe intellectual disability having higher diet scores, frequency scores, and susceptibility scores; hence lesser chances to avoid dental caries. Regular dental check-ups, including cleanings and other treatments if necessary, seem to be fundamental to prevent dental issues and maintain healthy teeth and gums for this group of people. Developing interventions that focus on improving oral health status among intellectually disabled individuals may be recommended to ensure the optimum level of support and reduce the burden of dental decay among those individuals.

7.
J Pharm Bioallied Sci ; 16(Suppl 1): S726-S729, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595412

RESUMEN

Background: The aim of this study was to evaluate the accuracy of the degree of fracture reduction after open reduction and internal fixation of Zygomaticomaxillary Complex (ZMC) fractures in the Saudi population of the Al-Baha region, using Gillies approach. Further comparison with preoperative and postoperative standardized computed tomography (CT) views with the calculation of residual deformity percentage, which remained after the ZMC rehabilitation. Methods: A 5-year retrospective CT-based study on preoperative and postoperative axial CT scans of 46 male patients with ZMC fractures. The CT measurements were made (in millimeters) at the fracture site of maximum displacement through the anterior orbital rim and orbital floor, posterolateral wall of the maxillary sinus, zygomatic arch, and zygomaticofrontal suture. For the zygomatic arch, measurements were made (in mm) by drawing a tangent to the fractured arch segments and dropping a perpendicular to the inward displaced fractured arch. The total difference in all measured parts between preoperative and postoperative displacement was calculated in percentages. Results: Upon comparison of preoperative and postoperative zygomaticomaxillary complex CTs, three-point fixation at the regions of infraorbital rim, frontozygomatic suture, and posterolateral wall of the maxilla results in a reduction of the fracture sites in the range of 72.85% to 85%. Maximum reduction was noted at the zygomatic arch, that is, 85%, and minimum at the infraorbital rim, that is, 72.85%. The reduction obtained at all four sites was statistically significant, with P values ranging from .011 to .039. Conclusion: Gillies temporal approach and three-point fixation at the regions of the infraorbital rim, frontozygomatic suture, and posterolateral wall of the maxilla results in satisfactory treatment of ZMC fractures and improves patients oral health and quality of life.

8.
Sci Rep ; 14(1): 16103, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997265

RESUMEN

High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G0-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G0-PCC-FISH, Dolphin's approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G0-PCC-Fragment assay (conventional G0-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G0-PCC-FISH was found to be most accurate for the dose estimation. G0-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.


Asunto(s)
Hibridación Fluorescente in Situ , Hibridación Fluorescente in Situ/métodos , Humanos , Aberraciones Cromosómicas/efectos de la radiación , Exposición a la Radiación/efectos adversos , Radiometría/métodos , Dosis de Radiación , Masculino , Relación Dosis-Respuesta en la Radiación
9.
Cureus ; 16(1): e51916, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38333482

RESUMEN

INTRODUCTION: The main feature of periodontitis is the development of periodontal pockets as a secondary consequence, which is mainly caused by an excessive immune response to the dental biofilm. The prime factor in the pathogenesis of periodontitis is an increase in oxidative stress. Numerous clinical studies have demonstrated that antioxidant supplementation can reduce endogenous antioxidant depletion and the oxidative damage that goes along with it. Hence, antioxidant therapy in the treatment of periodontal disease may prove to be a promising tool. OBJECTIVE: The objective of the study is to compare the efficiency of three different antioxidants as oral supplements. MATERIALS AND METHODS: Eighty patients with chronic periodontitis were randomly split into four groups. The control group received scaling and root planning (SRP), and the test group received oral supplements for 30 days with SRP. Pocket depth (PD), clinical attachment level (CAL), oral hygiene index-simplified (OHI-S), and sulcus bleeding index (SBI) were evaluated at baseline and 30 days. The analysis of the data was done with ANOVA, Kruskal-Wallis, and post hoc tests. The significance level was set at p<0.05 and p<0.001. RESULTS: All groups resulted in a statistically significant reduction in all parameters from baseline to one month. The treatment groups revealed a statistically significant reduction in PD and CAL (p<0.00) but no reduction in OHI-S and SBI (p>0.05) scores. A highly statistically significant reduction was observed in PD with green coffee bean extract when compared with other groups. CONCLUSION: Green coffee bean extract oral supplements may prove to be a promising appendage in therapeutic and prophylactic fashion, along with SRP, in the treatment of stage III grade B periodontitis patients.

10.
ACS Omega ; 8(36): 32512-32519, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37720789

RESUMEN

A gas sensor is a device that detects the presence of gases in a specific area. This research work demonstrates the effectiveness of gas sensors based on graphene oxide (GO) and copper oxide (CuO) semiconductor nanomaterials for the detection of carbon dioxide. GO and CuO were prepared by the modified Hummer's method and precipitation method using CuCl2 as a precursor, respectively. These materials are made into a hybrid using poly(vinyl alcohol) (PVA)/poly(vinylpyrrolidone) (PVP) polymer solutions of low concentrations and are spin coated onto the pattern-etched copper-clad substrate. The sensor is tested using a source measurement unit (SMU) to obtain the change in the resistance of the sensor in open air and in a carbon dioxide environment. The fabricated sensor with an Arduino microcontroller detection unit showed a good sensing response of 60%.

11.
Oral Health Prev Dent ; 10(4): 339-44, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23301234

RESUMEN

PURPOSE: To assess the knowledge, attitude, behavioural response and use of preventive measures regarding a pandemic H1N1 influenza outbreak among dental students. MATERIALS AND METHODS: In a cross-sectional study, a total of 448 dental students (118 in preclinical categories, 330 in clinical categories) were surveyed using a self-administered, structured questionnaire pretested through a pilot survey. RESULTS: Out of 448 dental students, 92.6% had heard about swine flu, whereas only 64.3% of them knew about the H1N1 virus. More than 50% of dental students showed a positive response towards swine flu attitude, and pandemic H1N1 influenza modified the behaviour of dental students. Respondents rated hand washing and face masks as the most effective measures for the prevention of pandemic influenza. CONCLUSION: Half of the dental students had enough information and showed a positive attitude towards a H1N1 pandemic influenza outbreak. However, the behavioural response of the participants was poor.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Gripe Humana/prevención & control , Gripe Humana/psicología , Pandemias/prevención & control , Estudiantes de Odontología/psicología , Adulto , Actitud del Personal de Salud , Estudios Transversales , Femenino , Desinfección de las Manos , Humanos , India/epidemiología , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Máscaras/estadística & datos numéricos , Factores Sexuales , Encuestas y Cuestionarios , Adulto Joven
12.
Front Public Health ; 10: 845200, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36003625

RESUMEN

A rapid and reliable method for biodosimetry of populations exposed to ionizing radiation in the event of an incident or accident is crucial for initial triage and medical attention. DNA-double strand breaks (DSBs) are indicative of radiation exposure, and DSB-repair proteins (53BP1, γH2AX, ATM, etc.) are considered sensitive markers of DSB quantification. Phospho-53BP1 and γH2AX immunofluorescence technique serves as a sensitive, reliable, and reproducible tool for the detection and quantification of DSB-repair proteins, which can be used for biological dose estimations. In this study, dose-response curves were generated for 60Co-γ-rays induced phospho-53 Binding Protein 1 (phospho-53BP1) foci at 1, 2, 4, 8, 16, and 24 h, post-irradiation for a dose range of 0.05-4 Gy using fluorescence microscopy. Following ISO recommendations, minimum detection limits (MDLs) were estimated to be 16, 18, 25, 40, 50, and 75 mGy for dose-response curves generated at 1, 2, 4, 8, 16, and 24 h post-irradiation. Colocalization and correlation of phospho-53BP1 and γH2AX were also measured in irradiated peripheral blood lymphocytes (PBLs) to gain dual confirmation. Comparative evaluation of the established curve was made by γH2AX-immunofluorescence, dicentric chromosome assay (DCA), and reciprocal translocation (RT) assays by reconstructing the dose of 6 dose-blinded samples. Coefficients of respective in-house established dose-response curves were employed to reconstruct the blind doses. Estimated doses were within the variation of 4.124%. For lower doses (0.052 Gy), phospho-53BP1 and γH2AX assays gave closer estimates with the variation of -4.1 to + 9% in comparison to cytogenetic assays, where variations were -8.5 to 24%. For higher doses (3 and 4 Gy), both the cytogenetic and immunofluorescence (phospho-53BP1 and γH2AX), assays gave comparable close estimates, with -11.3 to + 14.3% and -10.3 to -13.7%, variations, respectively.


Asunto(s)
Histonas , Triaje , Calibración , Análisis Citogenético , Rayos gamma , Histonas/metabolismo
13.
Chem Biol Interact ; 363: 109977, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-35636501

RESUMEN

Thorium (232Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. 232Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally. Monazite sand comprises of cerium and large quantities of radioactive thorium. The environmental hazard lies in monazite rich area being termed as High Background Radiation Area (HBRA). In this study, we mimicked the HBRA under controlled chamber conditions using thorium oxalate as a thorium source for BALB/c mice exposure. Furthermore, sequential radio-disintegration of 232 Th leads to thoron (220Rn), the noble gas and other daughter products/progeny predominantly via alpha decay/emissions. Such progeny tend to attach to aerosol and dust particles having potential inhalation hazard followed by alpha emissions and damages that we evaluated in mouse lung tissues post thoron inhalation. Secondly, along with the radio disintegration and alpha emission, high energy gamma is also generated that can travel to various distant organs through the systemic circulation, as significant findings of our study as damages to the liver and kidney. The mechanistic findings include the damages to the hematological, immunological and cellular antioxidant systems along with activation of canonical NF-κß pathway via double stranded DNA damage.


Asunto(s)
Contaminantes Radiactivos del Aire , Monitoreo de Radiación , Radón , Contaminantes Radiactivos del Aire/análisis , Animales , Antioxidantes , Riñón , Hígado , Pulmón/química , Ratones , Ratones Endogámicos BALB C , Hijas del Radón/análisis , Torio/análisis , Torio/toxicidad
14.
Dent Traumatol ; 27(5): 389-92, 2011 10.
Artículo en Inglés | MEDLINE | ID: mdl-21615860

RESUMEN

AIM: To compare the prevalence of anterior teeth fracture among sighted and visually impaired children of 12 and 15 years ages in Udaipur city, India. MATERIALS AND METHODS: A cross sectional study was carried out among 508 children (83 visually impaired and 425 sighted children), which comprised of 55 males and 28 females among visually impaired and 348 females and 77 males among sighted. The survey was carried out using Andreasen's classification for teeth fracture. Data was analyzed using chi-square test, with keeping level of significance at P < 0.05. RESULTS: It was found that, visually impaired children (32.5%) had significantly higher percentage of teeth fracture than that of sighted children (9.6%) (P = 001). Males had significantly higher percentage of teeth fracture than females in both groups (P = 0.001). It was observed that overjet of more than 3.5 mm had significantly increased risk of sustaining traumatic dental injuries among visually impaired (70.4%) than that of sighted individuals (46.3%) (P = 0.043). However, fracture of teeth was independent of age groups and lip coverage. CONCLUSION: Prevalence of traumatic dental injuries in a group of individuals with visual impairment was higher than that of sighted. This should alert caregivers to carry out a profound investigation of the events and suggest methods to reduce this type of morbidity.


Asunto(s)
Ceguera/complicaciones , Fracturas de los Dientes/complicaciones , Fracturas de los Dientes/epidemiología , Adolescente , Distribución de Chi-Cuadrado , Niño , Estudios Transversales , Diente Canino/lesiones , Femenino , Humanos , Incisivo/lesiones , India/epidemiología , Masculino , Maxilar , Sobremordida/complicaciones , Prevalencia , Factores Sexuales , Corona del Diente/lesiones
15.
Oral Health Prev Dent ; 9(3): 281-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22068185

RESUMEN

PURPOSE: To assess the oral hygiene and periodontal status and analyse the influence of age, education, institutionalization, type of visit and oral health behaviour on oral hygiene and periodontal status among detainees in juvenile detention center in Udaipur city, Rajasthan, India. MATERIALS AND METHODS: The total sample comprised 223 subjects (67.7% male and 32.3% female) aged 6 to 18 years. Clinical examination included assessment of oral hygiene and periodontal status using OHI-S (Oral Hygiene Index-Simplified) and CPI (Community Periodontal Index), respectively. Analysis of variance (ANOVA), chi-square, Student t-test and stepwise multiple linear and multiple logistic regression analysis were carried out to find the relation between oral hygiene/ periodontal status and different independent variables. RESULTS: The results showed that the oral hygiene status of detainees was poor, with only 28.1% of the subjects having good oral hygiene. Mean OHI-S scores were significantly associated with all independent variables. Overall periodontal disease prevalence was 80.2% with bleeding and calculus contributing a major part (71.9%). Stepwise multiple linear and logistic regression analysis revealed that oral hygiene practice and type of visit in the detention center were the best predictors for the oral hygiene index, and for periodontal disease it was oral hygiene practice alone. CONCLUSION: The findings confirmed that detainees in the juvenile detention center have poor oral hygiene and an increased prevalence of periodontal disease compared to that of similarly ages in the general population.


Asunto(s)
Delincuencia Juvenil , Índice de Higiene Oral , Índice Periodontal , Adolescente , Factores de Edad , Niño , Niño Institucionalizado/estadística & datos numéricos , Estudios Transversales , Cálculos Dentales/epidemiología , Depósitos Dentarios/epidemiología , Escolaridad , Femenino , Hemorragia Gingival/epidemiología , Conductas Relacionadas con la Salud , Humanos , India/epidemiología , Delincuencia Juvenil/estadística & datos numéricos , Masculino , Salud Bucal , Higiene Bucal/estadística & datos numéricos , Enfermedades Periodontales/epidemiología , Factores Sexuales , Cepillado Dental/estadística & datos numéricos , Pastas de Dientes/uso terapéutico
16.
Sci Rep ; 11(1): 13498, 2021 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-34188100

RESUMEN

Mitotic cell fusion induced Premature Chromosome Condensation (G0-PCC) assay in human lymphocytes allows rapid detection of cytogenetic damage in interphase stage, within few hours after blood collection. Hence, it is the most suitable method for rapid and high dose biodosimetry. Mitotic cells, used for G0-PCC could be either freshly isolated or previously cryo-preserved. However, under emergency scenarios, only cryo-preserved cells can be relied upon, fresh isolation will only delay the process by 18-24 h. Impact of cryopreservation on mitotic cells and their efficacy to induce PCC are not reported. In the present study, we investigated effect of cryopreservation on mitotic cells and refined the parameters for G0-PCC. More than 95% of the cells were recoverable after 4 months of cryopreservation, within 20 min recovery at 37 °C, without significant change in the mitotic index or viability. Recovered mitotic cells have shown mitotic index of 89 ± 4% and viability of 90 ± 4%, similar to that of freshly isolated cells. Decrease in metaphases was observed within 40 min after recovery as the mitotic cells progressed through cell cycle and reduced to 21% at 1.5 h. Nevertheless, in presence of Colcemid, the cells progressed slowly and considerably high metaphase index (60%) persisted up to ~ 2 h. The recovered cells efficiently fused with lymphocytes and induced PCC. Average PCC index varied from 10 to 20%, which did not change with cryopreservation duration. Post fusion incubation duration of 2 h was found to be optimum for proper chromosome condensation. In conclusion, use of cryo-preserved mitotic cells is the most practical approach for rapid biodosimetry. The cells can be recovered quickly and efficiently without alteration in viability or mitotic index. Recovered cells are fully competent to induce G0-PCC.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Cromosomas Humanos , Criopreservación , Rayos gamma/efectos adversos , Linfocitos/metabolismo , Mitosis/efectos de la radiación , Humanos , Linfocitos/patología , Dosis de Radiación , Radiometría
17.
Cancer Invest ; 28(6): 615-22, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20210520

RESUMEN

The aim of the current study was to determine the signaling differences between gamma- and proton beam-irradiations. A549 lung adenocarcinoma cells were irradiated with 2 Gy proton beam or gamma-radiation. Proton beam was found to be more cytotoxic than gamma-radiation. Proton beam-irradiated cells showed phosphorylation of H2AX, ATM, Chk2, and p53. The mechanism of excessive cell killing in proton beam-irradiated cells was found to be upregulation of Bax and downregulation of Bcl-2. The noteworthy finding of this study is the biphasic activation of the sensor proteins, ATM, and DNA-PK and no activation of ATR by proton irradiation.


Asunto(s)
Adenocarcinoma/patología , Apoptosis/efectos de la radiación , Daño del ADN , Rayos gamma , Neoplasias Pulmonares/patología , Protones , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Apoptosis/genética , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular/metabolismo , Muerte Celular/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Quinasa de Punto de Control 2 , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Histonas/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factores de Tiempo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo
18.
Mutat Res ; 699(1-2): 11-6, 2010 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-20338261

RESUMEN

The conventional dicentric assay does not provide an accurate dose estimate in the case of accidental exposure to ionizing radiation above 6 Gy due to mitotic delay and poor mitotic index. The present study aims to establish a simple and rapid dose assessment technique based on scoring of rings and fragments in PCC spreads of stimulated lymphocytes. Human peripheral blood lymphocytes were gamma irradiated to different doses (6.2-24.5 Gy), cultured for two days with PHA and were forced to condense prematurely using 500 nM Okadaic acid (OA). The chromosome spreads were prepared, stained with Giemsa and observed under a microscope. The PCC index, PCC rings, and PCC fragments were scored for each dose point to arrive at the dose effect curve for various end points such as induction of rings and fragments and dicentrics. The PCC index varied from 12-18% up to 18 Gy and thereafter dropped to 6-8% at higher doses. The dose dependent increase in rings and fragments was found to be linear with a slope of 0.054+/-0.001 Gy(-1) for rings and 0.45+/-0.03 Gy(-1) for PCC fragments. An experiment was carried out to simulate partial-body exposure by mixing 10 Gy in vitro irradiated blood with un-irradiated blood in different proportions. The ratio of frequency of damaged cells among the total number of cells analyzed was found to be a good index of partial-body exposure. The culture duration was extended to 72 h to overcome the cell cycle delay induced by high doses of radiation. The conventional dicentrics rings and fragments also showed a dose response at high doses. The response can be best fitted to a linear model with a slope of 0.28+/-0.0007 Gy(-1) for the induction of dicentrics. However, long culture duration, technical skill and time required to analyse multi-aberrant cells makes the dicentric assay less suitable for high dose exposures requiring a rapid dose estimate. The PCC assay can be performed in 50 h with biodosimetric information about the irradiated fraction in cases of acute radiation exposures. The automated finding of PCC spreads significantly increased the speed of scoring PCC fragments.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos/efectos de la radiación , Rayos gamma , Dosis de Radiación , Liberación de Radiactividad Peligrosa , Radiometría/métodos , Adulto , Células Cultivadas , Aberraciones Cromosómicas/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Ácido Ocadaico/farmacología , Estudios de Validación como Asunto
19.
Int J Radiat Biol ; 96(10): 1274-1280, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32689847

RESUMEN

BACKGROUND: Biodosimetry with persistent cytogenetic indicators in peripheral blood lymphocytes (PBLs) plays crucial role in regulatory/medical management of individuals overexposed to radiation. Conventional methods require ∼48 h culture and have limited dose range (0.1-5Gy) applications due to checkpoint arrest/poor stimulation. G0-Phase Premature chromosome condensation (G0-PCC) allows chromosome aberration analysis within hours after blood collection. Due to high skill demand, applications of G0-PCC were not very well explored and being re-visited worldwide. Among all aberrations, analysis of excess chromosomal fragments is quickest. Radiation dose response curve for the fragments has been reported. PURPOSE: In present study, excess fragment analysis has been addressed in detail, in addition to validation of radiation dose response curve, gender variation in the response, dose dependent repair kinetics, minimum detection limit (MDL), duration and accuracy of final dose estimation with 5blindfolded, ex vivo irradiated samples have been studied. In extension, feasibility of multiparametric dosimetry with Fluorescent in situ hybridization (FISH) based endpoints were qualitatively explored. MATERIAL AND METHODS: PBLs were exposed to Gamma-Radiation and G0-PCC was performed at different time points. Decay kinetics and dose response curve were established. Gender Variation of the frequency of the fragments was assessed at 0, 2 and 4 Gy. FISH was performed with G0-PCC applying centromere probe, whole chromosome paints, multi-color FISH and multi-color banding probes. RESULTS: Radiation response curve for fragments was found to be linear (Slope 1.09 ± 0.031 Gy-1). Background frequency as well as dose response did not show significant gender bias. Based on variation in background frequency of fragments MDL was calculated to be ∼0.3 Gy. Kinetics of fragment tested at 0, 4, 8, 16 and 24 h showed exponential decay pattern from 0 to 8 h and without further decay. Final dose estimation of five samples was completed within 13 man-hours. Dicentric chromosomes, translocations, insertions and breaks were identifiable in combination with centromere FISH and WCP. Advanced methods employing multicolor FISH and multi-color banding were also demonstrated with PCC spreads. CONCLUSION: G0-PCC, can be useful tool for high dose biodosimetry with quick assessment of fragment frequency. Further, it holds potential for multi-parametric dosimetry in combination with FISH.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Animales , Células CHO , Cricetulus , Relación Dosis-Respuesta en la Radiación , Reordenamiento Génico/efectos de la radiación , Hibridación Fluorescente in Situ , Cinética , Radiometría
20.
Int J Radiat Biol ; 96(11): 1362-1373, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32910703

RESUMEN

PURPOSE: Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (222Rn)/thoron (220Rn) and their progenies. Hence, we reviewed the biological effects of 222Rn/220Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by 222Rn/220Rn and their progenies. MATERIALS AND METHOD: We have extensively reviewed articles among several hits obtained in PubMed, Scopus, and Elsevier databases with keywords 'Radon/Thoron' OR Thoron progeny/Radon progeny OR 'Thoron/Radon inhalation and lungs', and proceed for further analysis. Also, databases related to oxidative damage to lung stem cells by radiation and the repair mechanisms involved by the lung stem cells were also included. RESULTS: Based on the existing epidemiological data on radon in residential buildings, we found that evidence exists on the association of radon induced lung carcinogenesis, but the data regarding the role of thoron induced lung damage is very limited and inconclusive. We also found that limited information has been provided based on ecological designs, leading to poor documentation of health statistics, in particular, organ-specific cancer rates. Finally, we tried to elucidate the possible mechanisms of lung injury induced by thoron inhalation and the probable role of lung stem cell toward the redemption of such oxidative damages. CONCLUSION: Existing epidemiological data on thoron inhalation and associated health outcomes are limited and inconclusive. Further, in vivo experiments, with respect to radon/thoron inhalation dose rate ranges corresponding to the HNBR areas will be helpful in understanding the cellular and molecular effects.


Asunto(s)
Pulmón/patología , Pulmón/efectos de la radiación , Radón/efectos adversos , Células Madre/citología , Animales , Radiación de Fondo/efectos adversos , Ambiente , Humanos , Células Madre/efectos de la radiación
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