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1.
Cell Biochem Funct ; 42(1): e3903, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269508

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch-like ECH-associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ-H2AX in MCF-7 and MDA-MB-231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner. Further we observed that auranofin and paclitaxel treatment prevents the translocation of Nrf2 in a concentration dependent manner. The increased FOXO3 expression might be involved in the cytoplasmic degradation of Nrf1-Keap1 complex. Further, the molecular docking results confirm auranofin act as the agonist for Foxo3. Therefore, the present results suggest that auranofin sensitize the breast cancer cells to paclitaxel via regulating FOXO3/Nrf2/Keap1signaling pathway.


Assuntos
Neoplasias , Paclitaxel , Paclitaxel/farmacologia , Auranofina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Simulação de Acoplamento Molecular , Transdução de Sinais , Morte Celular
2.
Int J Clin Pediatr Dent ; 16(2): 280-286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519972

RESUMO

Context: Molar incisor hypomineralization (MIH) is an emerging clinical problem as the affected tooth is prone to dental caries with the lapse of time. Aims: To assess the prevalence, severity, and associated risk indicators of MIH amongst 8-13 years of children of Vadodara District, Gujarat, India. Materials and methods: A cross-sectional study with a sample size of 3,000 government schoolchildren. A total of 1,500 children each from urban and rural areas were randomly selected and examined. Only permanent incisors and first molars were examined. MIH was diagnosed clinically based on the diagnostic criteria established by the European Academy of Paediatric Dentistry (EAPD), 2003. To check the relation between the two variables-Pearson's chi-squared test was applied. Fisher's exact test was applied when less than five expected values were found. Results: A total of 286 children (9.6 %) had MIH, with 189 (rural) and 97 (urban) children. MIH was significantly higher in the rural population as compared to the urban. In the rural area, the cause was found to be a child suffering from an illness (>15 days) which was 35.98%, and in the urban area was due to prolonged use of antibiotics before 4 years of age, which was 28.87%. Conclusion: The overall prevalence rate of MIH among the screened children between the age-group 8 and 13 was found to be 9.6%. Males were more affected. The severity of MIH was more in molars compared to incisors and more in children of rural areas. Clinical significance: Protocol for early diagnosis and follow-up to access the squeal of breakdown should be undertaken along with parents and health workers. How to cite this article: Shah VU, Dave BH, Chari DN, et al. Prevalence, Severity and Associated Risk Indicators of Molar Incisor Hypomineralization amongst 8-13-year-old Children of Vadodara District Gujarat: A Cross-sectional Study. Int J Clin Pediatr Dent 2023;16(2):280-286.

3.
CNS Neurol Disord Drug Targets ; 22(6): 801-816, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35546747

RESUMO

Parkinson's Disease (PD), known as Parkinsonism, is a neurodegenerative disease that mainly affects the elderly and is characterized by an extensive and progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc). Owing to genetic, environmental, and lifestyle changes, the incidence of PD has recently risen among adults. The most widely used PD treatment strategies include the use of dopamine agonists, anticholinergics, and enzyme inhibitors. The aquatic flora and fauna have become the emerging source of novel, structurally diverse bioactive compounds and, at present, the researchers concentrate their efforts on isolating, characterizing, and identifying many secondary metabolites of different nature to treat various disorders, including, neuroprotective marine natural products (MNPs). The bioactive peptides, tannins, carotenoids, alkaloids, polyunsaturated fatty acids (PUFA), and sulfated polysaccharides from the MNP's and their synthetic derivatives have demonstrated important neuroprotective activity in preclinical studies through multiple mechanisms. An extensive literature survey was carried out, and published articles from PubMed, Scifinder, Google Scholar, Web of Science, and Scopus were carefully reviewed to compile information on the MNPs to treat PD. This current review focus on neuroprotective MNPs and their probable biological pathways to treat PD based on their structure and bioactivities reported from 1990 to 2020.


Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Idoso , Doença de Parkinson/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Neurônios Dopaminérgicos/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia
4.
Ann Otol Rhinol Laryngol ; 132(10): 1140-1148, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36514234

RESUMO

OBJECTIVE: To compare the effect of virtual and in-person head and neck physical examination training events on medical student confidence in performing examination maneuvers and seeking mentorship from otolaryngology faculty and residents. METHODS: Training events were held with first-year medical student volunteers in 2020 (in-person) and 2021 (virtual). Participants in both cohorts were given didactics on head and neck cancer, trained to perform a head and neck physical examination, and demonstrated their clinical skills to otolaryngology faculty and residents. Pre- and post-training surveys were utilized to assess the following outcomes: participant head and neck cancer knowledge, confidence in performing examination maneuvers, and confidence in seeking mentorship in otolaryngology. Differences in outcomes between training settings were assessed by comparing participant survey responses pre- and post- training. RESULTS: Both in-person and virtual training modalities improved participant confidence in performing the physical examination. There was no significant difference in the degree of improvement between training types. In-person training significantly increased participant confidence in seeking mentorship from otolaryngology faculty and residents (P = .003), while virtual training did not (P = .194). CONCLUSION: Virtual training modalities are feasible methods of teaching the head and neck physical examination. Instruction through a video conferencing platform has the potential to be incorporated into traditional in-person medical education in a permanent fashion. This pilot study can inform future studies directly comparing in-person and virtual physical examination training modalities.


Assuntos
Otolaringologia , Estudantes de Medicina , Humanos , Projetos Piloto , Pescoço , Exame Físico , Otolaringologia/educação , Competência Clínica
5.
Contemp Clin Dent ; 14(4): 289-292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38344155

RESUMO

Aim and Objectives: Estimation and correlation of plasma fibrinogen degradation product (FDP) and salivary fibrin precipitating factor (FPF) in oral sub mucous fibrosis (OSMF) patients, betel quid chewers without OSMF and healthy individuals. The study aims to evaluate whether FDP and FPF can be used as a marker for development and progression of OSMF and whether there is any correlation between the two. Methodology: The study included 163 subjects grouped into three categories, Group 1, which included 54 control patients, Group 2, which included 55 betel quid chewers, and Group 3, which included 54 clinically confirmed OSMF patients. All of them were subjected to the estimation of plasma FDP and salivary FPF. Results: FDP was present in 52 (96.3%) patients in Group 3, 2 (3.6%) patients in Group 2, and 1 patient in Group 1 (1.9%). FPF was positive in eight patients. The correlation of FDP and FPF was done by Fisher's exact test and was found to be statistically nonsignificant. Conclusion: In the present study, FDP was positive in 52 (96.3%) OSMF patients; hence, FDP may be used as an early indicator of OSMF. FDP was found to be positive in two patients with a habit of chewing betel quid without OSMF. It may be hypothesized that these patients are more likely to develop OSMF. Hence, the estimation of FDP may be used as a diagnostic test to predict an impending OSMF before it could manifest itself clinically. FPF was negative in some OSMF patients, may be because it is below the detectable range.

6.
Matern Child Nutr ; 18(3): e13320, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35307937

RESUMO

The objective of this study was to assess public financing for nutrition in Bhutan, Nepal and Sri Lanka to identify limitations of available data and to discuss policy implications. A variant of the Scaling Up Nutrition Movement methodology was used. Budget allocations and expenditures for relevant government ministries during 2012-2018 were identified. Nutrition-related line items were tagged using definitions of nutrition-specific and nutrition-sensitive interventions. Data were aggregated by year and calculated in constant United States dollars (USD). Expenditures by year were presented as a proportion of gross domestic product and general government expenditures. The percent utilization of budget allocations and proportion of funding from central government sources were determined. Per capita expenditures on nutrition-specific interventions varied from USD 1.08-8.76 and for nutrition-sensitive interventions varied from USD 20.22-51.20. Nutrition-specific expenditures as a percent of gross domestic product ranged from 0.08% in Sri Lanka in 2017% to 0.34% in Nepal in 2016. The median utilization rate was 64% for nutrition-specific and 84% for nutrition-sensitive interventions. Nutrition-specific funding financed by the central government was 90.7% in Bhutan and 99.4% in Sri Lanka. This study revealed the need to prioritize and invest in evidence-based interventions, including balancing investments in nutrition-specific versus -sensitive interventions. Challenges in estimation of nutrition expenditures and cross-country comparison were also observed, highlighting the need for appropriate nutrition line item tagging and standardized systems for data collection.


Assuntos
Financiamento Governamental , Estado Nutricional , Butão , Humanos , Nepal , Sri Lanka
7.
Ann Otol Rhinol Laryngol ; 131(12): 1353-1357, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35021910

RESUMO

OBJECTIVE: Medical podcasts are becoming increasingly available; however, it is unclear how these new resources are being used by trainees or whether they influence clinical practice. This study explores the preferences and experiences of otolaryngology residents with otolaryngology-specific podcasts, and the impact of these podcasts on resident education and clinical practice. METHODS: An 18-question survey was distributed anonymously to a representative junior (up to post-graduate year 3) and senior (post-graduate year 4 or greater) otolaryngology residents at most programs across the US. Along with demographic information, the survey was designed to explore the preferences of educational materials, podcast listening habits and motivations, and influence of podcasts on medical practice. Descriptive statistics and student t-tests were used to analyze the results. RESULTS: The survey was distributed to 198 current otolaryngology residents representing 94% of eligible residency programs and was completed by 73 residents (37% response rate). Nearly 3-quarters of respondents reported previous use of otolaryngology podcasts, among which 83% listen at least monthly. Over half of residents changed their overall clinical (53%) and consult (51%) practice based on podcast use. Residents rank-ordered listening to podcasts last among traditional options for asynchronous learning, including reading textbooks and watching online videos. CONCLUSIONS: While other asynchronous learning tools remain popular, most residents responding to this survey use podcasts and report that podcasts influence their clinical practice. This study reveals how podcasts are currently used as a supplement to formal otolaryngology education. Results from the survey may inform how medical podcasts could be implemented into resident education in the future.


Assuntos
Internato e Residência , Otolaringologia , Escolaridade , Humanos , Aprendizagem , Otolaringologia/educação , Inquéritos e Questionários
8.
Nat Prod Res ; 35(3): 413-420, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31311318

RESUMO

Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae) is the most important plant in the herbal remedies. The present study focus on the isolation, in-silico and in-vitro studies of the two alkaloids C1 (5-(4-[(methylcarbamoyl) amino]-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl methyl carbamate is novel alkaloid and C2 13-Docosenamide is a known alkaloid. The chemical structures of compounds have been elucidated based on comprehensive techniques like GCMS, IR and NMR. In order to know the molecular mechanisms for the two compounds, in silico molecular docking study has been performed. Both compounds have shown perfect binding affinity to the enzymes TNF α, IL-4, IL-13 and 5 LOX Enzyme. The compounds also exhibited comparable G-scores and Glide energy values in comparison with the standard dexamethasone. In addition both the compounds have been tested for in vitro antioxidant assay by using ABTS and DPPH method and the results were compared with standard ascorbic acid.


Assuntos
Alcaloides/química , Alcaloides/metabolismo , Fabaceae/química , Alcaloides/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Simulação por Computador , Ácidos Erúcicos/química , Ácidos Erúcicos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Interleucina-13/química , Interleucina-13/metabolismo , Interleucina-4/química , Interleucina-4/metabolismo , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Pirimidinas/química , Fator de Necrose Tumoral alfa/química , Fator de Necrose Tumoral alfa/metabolismo
9.
Am J Ophthalmol ; 218: 279-287, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32621891

RESUMO

PURPOSE: This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. RESULTS: A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and "other" forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. CONCLUSIONS: Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.


Assuntos
Corioidite/epidemiologia , Oftalmia Simpática/epidemiologia , Descolamento Retiniano/epidemiologia , Uveíte Posterior/epidemiologia , Síndrome Uveomeningoencefálica/epidemiologia , Adulto , Exsudatos e Transudatos , Feminino , Angiofluoresceinografia , Humanos , Incidência , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acuidade Visual/fisiologia
10.
Expert Rev Med Devices ; 16(7): 603-616, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31154869

RESUMO

INTRODUCTION: Blood-recirculating medical devices, such as mechanical circulatory support (MCS), extracorporeal membrane oxygenators (ECMO), and hemodialyzers, are commonly used to treat or improve quality of life in patients with cardiac, pulmonary, and renal failure, respectively. As part of their regulatory approval, guidelines for thrombosis evaluation in pre-clinical development have been established. In vitro testing evaluates a device's potential to produce thrombosis markers in static and dynamic flow loops. AREAS COVERED: This review focuses on in vitro static and dynamic models to assess thrombosis in blood-recirculating medical devices. A summary of key devices is followed by a review of molecular markers of contact activation. Current thrombosis testing guidance documents, ISO 10993-4, ASTM F-2888, and F-2382 will be discussed, followed by analysis of their application to in vitro testing models. EXPERT OPINION: In general, researchers have favored in vivo models to thoroughly evaluate thrombosis, limiting in vitro evaluation to hemolysis. In vitro studies are not standardized and it is often difficult to compare studies on similar devices. As blood-recirculating devices have advanced to include wearable and implantable artificial organs, expanded guidelines standardizing in vitro testing are needed to identify the thrombotic potential without excessive use of in vivo resources during pre-clinical development.


Assuntos
Equipamentos e Provisões , Modelos Biológicos , Trombose/diagnóstico , Materiais Biocompatíveis/farmacologia , Biomarcadores/metabolismo , Humanos , Qualidade de Vida , Trombose/terapia
11.
PLoS One ; 12(9): e0185030, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28931088

RESUMO

BACKGROUND: Undernutrition below two years of age remains a major public health problem in India. We conducted an evaluation of an integrated nutrition and health program that aimed to improve nutritional status of young children by improving breast and complementary feeding practices over that offered by the Government of India's standard nutrition and health care program. METHODS: In Uttar Pradesh state, through multi-stage cluster random sampling, 81 villages in an intervention district and 84 villages in a comparison district were selected. A cohort of 957 third trimester pregnant women identified during house-to-house surveys was enrolled and, following childbirth, mother-child dyads were followed every three months from birth to 18 months of age. The primary outcomes were improvements in weight-for-age and length-for-age z scores, with improved breastfeeding and complementary feeding practices as intermediate outcomes. FINDINGS: Optimal breastfeeding practices were higher among women in intervention than comparison areas, including initiating breastfeeding within one hour of delivery (17.4% vs. 2.7%, p<0.001), feeding colostrum (34.7% vs. 8.4%, p<0.001), avoiding pre-lacteals (19.6% vs. 2.1%, p<0.001) and exclusively breastfeeding up to 6 months (24.1% vs. 15.3%, p = 0.001). However, differences were few and mixed between study arms with respect to complementary feeding practices. The mean weight-for-age z-score was higher at 9 months (-2.1 vs. -2.4, p = 0.0026) and the prevalence of underweight status was lower at 12 months (58.5% vs. 69.3%, p = 0.047) among intervention children. The prevalence of stunting was similar between study arms at all ages. Coefficients to show the differences between the intervention and comparison districts (0.13 cm/mo) suggested significant faster linear growth among intervention district infants at earlier ages (0-5 months). INTERPRETATION: Mothers participating in the intervention district were more likely to follow optimal breast, although not complementary feeding practices. The program modestly improved linear growth in earlier age and weight gain in late infancy. Comprehensive nutrition and health interventions are complex; the implementation strategies need careful examination to improve feeding practices and thus impact growth. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, NCT00198835.


Assuntos
Aleitamento Materno , Fenômenos Fisiológicos da Nutrição do Lactente , Estado Nutricional , Aleitamento Materno/estatística & dados numéricos , Feminino , Promoção da Saúde , Humanos , Índia , Lactente , Estudos Longitudinais , Mães , Programas Nacionais de Saúde , Gravidez , Fatores Socioeconômicos
12.
PLoS One ; 12(9): e0183316, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28910328

RESUMO

BACKGROUND: Integrated nutrition and health programs seek to reduce undernutrition by educating child caregivers about infant feeding and care. Data on the quality of program implementation and consequent effects on infant feeding practices are limited. This study evaluated the effectiveness of enhancing a nutrition and health program on breastfeeding and complementary-feeding practices in rural India. METHODS: Utilizing a quasi-experimental design, one of the implementing districts of a Cooperative for Assistance and Relief Everywhere (CARE) nutrition and health program was randomly selected for enhanced services and compared with a district receiving the Government of India's standard nutrition and health package alone. A cohort of 942 mother-child dyads was longitudinally followed from birth to 18 months. In both districts, the evaluation focused on responses to services delivered by community-based nutrition and health care providers [anganwadi workers (AWWs) and auxiliary nurse midwives (ANMs)]. FINDINGS: The CARE enhanced program district showed an improvement in program coverage indicators (e.g., contacts, advice) through outreach visits by both AWWs (28.8-59.8% vs. 0.7-12.4%; all p<0.05) and ANMs (8.6-46.2% vs. 6.1-44.2%; <0.05 for ages ≥6 months). A significantly higher percentage of child caregivers reported being contacted by the AWWs in the CARE program district (20.5-45.6% vs. 0.3-21.6%; p<0.05 for all ages except at 6months). No differences in ANM household contacts were reported. Overall, coverage remained low in both areas. Less than a quarter of women received any infant feeding advice in the intervention district. Earlier and exclusive breastfeeding improved with increasing number or quality of visits by either level of health care provider (OR: 2.04-3.08, p = <0.001), after adjusting for potentially confounding factors. Socio-demographic indicators were the major determinants of exclusive breastfeeding up to 6 month and age-appropriate complementary-feeding practices thereafter in the program-enhanced but not comparison district. INTERPRETATION: An enhanced nutrition and health intervention package improved program exposure and associated breastfeeding but not complementary-feeding practices, compared to standard government package. TRIAL REGISTRATION: ClinicalTrials.gov NCT00198835.


Assuntos
Cuidadores/educação , Educação em Saúde/estatística & dados numéricos , Promoção da Saúde/organização & administração , Aleitamento Materno , Feminino , Educação em Saúde/organização & administração , Promoção da Saúde/estatística & dados numéricos , Humanos , Índia , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estado Nutricional , Avaliação de Programas e Projetos de Saúde , Saúde da População Rural , Serviços de Saúde Rural
13.
J Clin Orthop Trauma ; 7(Suppl 1): 76-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28018079

RESUMO

Aberrant insertions of the pectoralis minor tendon are quite rare. Most cases are incidental findings during cadaver dissections, on an MRI or during surgical procedures of the shoulder joint. Rarely the aberrant insertion points can be a source of pain or restriction of the shoulder joint. From the literature review, we found that there has been no mention regarding the frequency of occurrence of this variation with respect to unilateral or bilateral occurence, and only three cases have been reported, in which aberrant bilateral insertions have been documented of which two were noted during cadaveric dissection and one radiologically. We report a rare case of aberrant bilateral insertions of the pectoralis minor, which was found during an arthroscopic procedure, and we discuss its clinical and surgical implications.

14.
J Fluoresc ; 26(6): 2119-2132, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27589976

RESUMO

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.


Assuntos
Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Citotoxinas/farmacologia , Clivagem do DNA/efeitos dos fármacos , DNA/metabolismo , Compostos Organometálicos/farmacologia , Rutênio/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Sítios de Ligação , Bovinos , Ciclo Celular/efeitos dos fármacos , Complexos de Coordenação/química , Citotoxinas/química , Clivagem do DNA/efeitos da radiação , Células HeLa , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Ligantes , Testes de Sensibilidade Microbiana , Compostos Organometálicos/química
16.
Oncotarget ; 6(17): 15594-609, 2015 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-25909225

RESUMO

A current challenge in prostate cancer treatment is how to differentiate aggressive disease from indolent prostate cancer. There is an urgent need to identify markers that would accurately distinguish indolent prostate cancer from aggressive disease. The aim of this study was to evaluate the role of PDZ Domain-binding kinase (PBK) in prostate cancer and to determine if PBK expression enhances aggressiveness in prostate cancer. Using archival tissue samples, gain-of-function and loss-of-function studies, we show that PBK expression is up-regulated in prostate cancer, and its expression level is commensurate with invasiveness. Modulation of PBK expression and function causally regulates the invasive ability of prostate cancer cells. Production of matrix metalloproteinases-2 and -9, which are key players in metastatic invasion, is up-regulated, and the promoters of these genes are transcriptionally activated by PBK via increased ß-catenin-TCF/LEF signaling. Prostate cancer tissue specimens show that PBK's expression correlates with aggressive disease and distant metastasis in bone, lymph node and abdomen. Our in vitro and in situ data are in agreement that PBK could be a prognostic biomarker for prostate cancer that would discriminate aggressive prostate cancer from indolent disease, and is a potential target for the therapeutic intervention of aggressive prostate cancer in men.


Assuntos
Biomarcadores Tumorais/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neoplasias da Próstata/patologia , Fatores de Transcrição TCF/metabolismo , beta Catenina/metabolismo , Neoplasias Abdominais/secundário , Biomarcadores Tumorais/genética , Neoplasias Ósseas/secundário , Linhagem Celular Tumoral , Movimento Celular , Humanos , Metástase Linfática/patologia , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Invasividade Neoplásica , Regiões Promotoras Genéticas/genética , Transdução de Sinais
17.
Semin Ophthalmol ; 29(5-6): 363-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25325862

RESUMO

Femtosecond-assisted laser in-situ keratomileusis flaps have revolutionized refractive surgery since their introduction. Although these lasers are exceedingly safe, complications still do occur. This review focuses specifically on examining the literature and evidence for flap complications during femtosecond-assisted laser in-situ keratomileusis as well as their management.


Assuntos
Substância Própria/cirurgia , Complicações Intraoperatórias , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Complicações Pós-Operatórias , Retalhos Cirúrgicos/efeitos adversos , Humanos , Hiperopia/cirurgia , Miopia/cirurgia
18.
Eur J Med Chem ; 72: 160-9, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24418931

RESUMO

Three new compounds, [Ru(Hdpa)2PyIP](ClO4)2·2H2O (1) [Ru(Hdpa)2FyIP](ClO4)2·2H2O (2) and [Ru(Hdpa)2IIP](ClO4)2·2H2O (3) have been synthesized and characterized by spectroscopic techniques such as elemental analysis, UV/Vis, FT-IR, (1)H NMR, (13)C NMR and mass spectra. The CT-DNA binding properties of 1-3 have been investigated by absorption, emission spectroscopy and viscosity measurements. Experimental results suggested that they can interact with DNA through intercalative mode with different binding strengths. These were found to promote the cleavage of plasmid DNA. Cell viability results indicated that all compounds showed significant dose dependent cytotoxicity in selected cell lines and 1 shown higher cytotoxicity than cisplatin on HeLa cells. Cellular uptake studies were studied by flow cytometry and confocal microscopy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rubídio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade
19.
Eur J Med Chem ; 64: 410-21, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23665797

RESUMO

In an endeavor toward the development of metal-based anticancer drugs, we present here the design, synthesis and characterization of three ruthenium(II) functionalized phenanthroline complexes with extended π-conjugation. These complexes have been shown to act as promising CT-DNA intercalators as evidenced by UV-visible, luminescence, emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide and salt dependent studies. All three complexes [Ru(Hdpa)2PPIP](2+) (1), [Ru(Hdpa)2PIP](2+) (2), [Ru(Hdpa)24HEPIP](2+) (3) clearly demonstrated that they can bind to DNA through the intercalation mode. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The apoptosis and cell cycle arrest were also investigated. The complexes were docked into DNA-base-pairs using the 'GOLD' (Genetic Optimization for Ligand Docking), docking program.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rutênio/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Bovinos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade
20.
J Fluoresc ; 23(5): 897-908, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23553642

RESUMO

Three Ruthenium(II) polypyridine complexes, [Ru(phen)2(mipc)](2+)(1), [Ru(bpy)2(mipc)](2+) (2) and [Ru(dmb)2(mipc)](2+)(3) [mipc = 2-(6-methyl-3-(1H-imidazo[4, 5-f][1,10]-phenanthroline-2-yl)-4H-chromene-4-one, phen = 1,10-phenanthroline,bpy = 2, 2'bipyridine,dmb = 4, 4'-dimethyl-2, 2'-bipyridine] have been synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H& (13)C NMR and mass spectra. The DNA-binding properties of the Ruthenium(II) complexes were investigated by spectrophotometric methods, viscosity measurements and light switch studies. These three complexes have been focused on photo activated cleavage studies with pBR-322 and antimicrobial studies. Experimental results indicate that the three complexes intercalate into DNA base pairs and follows the order of 1 > 2 > 3 respectively. Molecular docking studies also support the DNA interactions with complexes through hydrogen bonding and vander Waal's interactions. Cytotoxicity studies with Hela cell lines has been revealing about anti tumor activity of these complexes.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , DNA/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rutênio/química , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Clivagem do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Células HeLa , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Processos Fotoquímicos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
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