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1.
Appl Opt ; 63(4): 1058-1065, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437404

RESUMO

Chromatic dispersion (CD) is a major concern in high speed fiber optics communication systems. This work presents an efficient optical compensation technique with reduced complexity to mitigate CD effects in single mode fiber (SMF) at high data rates. The proposed method includes a post-dispersion mitigation system using a single linear chirped fiber Bragg grating (CFBG) with tanh apodization. Here, various parameters of CFBG, such as grating length, effective refractive index, and apodization function, are optimized to achieve effective CD compensation. Then, the system is extended to a 16-channel WDM link with each channel carrying data at 25 Gbps over 100 km. The simulation results show that the proposed model enhances the system performance while minimizing overall system complexity. The proposed system is also compatible with the prevailing fiber optics networks. The results are consistent with the findings published in recent studies.

2.
J Neonatal Perinatal Med ; 15(2): 367-372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34806621

RESUMO

Neonatal myocardial infarction due to coronary thrombus is a rare cause of acute heart failure and is associated with high morbidity and mortality. We present a rare case of a full-term newborn who developed coronary artery thrombus treated with intracoronary recombinant tissue plasminogen activator infusion while undergoing therapeutic hypothermia. Also, we describe a unique treatment strategy to support systemic circulation sparing the patient from neonatal extracorporeal membrane oxygenation and its complications. Neonatal myocardial infarction should be suspected and ruled out in sick newborns.


Assuntos
Oxigenação por Membrana Extracorpórea , Infarto do Miocárdio , Trombose , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Recém-Nascido , Infarto do Miocárdio/tratamento farmacológico , Gravidez , Trombose/complicações , Trombose/etiologia , Ativador de Plasminogênio Tecidual/uso terapêutico
3.
J Ayurveda Integr Med ; 12(4): 695-699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34740494

RESUMO

BACKGROUND: Current medical intervention of Polycystic Ovarian Syndrome (PCOS) mainly includes hormonal therapies which have long-term health consequences. OBJECTIVE: This study aimed to evaluate the effect of natural drug satapushpa (Anethum sowa Kurz.) powder with tilatailam (sesame oil) as anupanam (vehicle) in oligomenorrhoea associated with PCOS. MATERIALS AND METHODS: A single-group, before and after intervention study in the outpatient department and inpatient department of Government Ayurveda teaching hospital for women and children was done among women aged 18-35 years. Individuals diagnosed with oligomenorrhoea for more than three consecutive menstrual cycles and fulfilling Rotterdam's criteria of PCOS were included. Six grams of powder was given morning and evening along with 12 ml of tilatailam for three months. Effectiveness was assessed at 3rd and 6th months. RESULTS: A total of 30 patients were recruited; the mean (SD) age was 22.6 (3.9) years. Majority were students (86.7%), residing in urban areas (60%), and unmarried (80%). Almost one-third of the participants had kapha-vata prakriti. There was no significant change in menstrual duration and amount of bleeding. However, a significant reduction in the menstrual interval was observed after three months of treatment (p = <0.001). Similarly, the median interquartile range (IQR) volume of the right ovary was reduced from 10 (7.2-14.8) to 5.3 (4.7-7.6) cm3 (p=<0.001), and the median (IQR) volume of the left ovary reduced from 9.1 (6.7-11.9) to 5.1 (4.6-7.1) cm3 (p=<0.001). CONCLUSION: Treating PCOS using satapushpa powder and tilatailam for three months effectively regularizes the menstrual interval and reduces ovarian volume.

4.
Dent Res J (Isfahan) ; 17(5): 373-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343846

RESUMO

BACKGROUND: The aim of the study was to assess the relationship between height and dental caries among 13-year-old adolescents in schools of Bangalore, India. MATERIALS AND METHODS: A cross-sectional study was undertaken on 1900 schoolchildren aged 13 years from both government and private schools of Bangalore using stratified random sampling. Demographic data; family-related factors; and general and oral health-related factors such as frequency of sugar consumption, dietary habits, oral hygiene practices, and dental attendance were interviewed using both open-ended and close-ended questions. Anthropometric measurements for height and weight were performed. Clinical examination was done and caries was recorded using the decayed, missing, and filled teeth (DMFT) index (WHO criteria, 1997). Data were analyzed using SPSS version 21.0, and descriptive statistics including percentages, mean, and frequencies were performed. Student's t-test and ANOVA were applied to find the significant differences between mean DMFT among groups. Categorical data were analyzed by Chi-square test for differences between groups. Pearson correlation coefficient was used to find the correlation among dental caries and height and body mass index (BMI).P value was set at a statistical significance level of 0.05. RESULTS: The prevalence of dental caries among the study population was 36.3% which was higher among girls as compared to boys. Dental caries was found to be significantly associated with socioeconomic status, family structure, birth order, use of oral hygiene aids, mouthrinsing, last dental visit, weight, and BMI. Height and BMI showed a strong negative correlation with dental caries. CONCLUSION: The present study showed a significant negative correlation between height and dental caries. However, since both caries and height are a dynamic phenomenon, hence a longitudinal study exploring the possible relationship should be considered.

5.
BMC Pediatr ; 17(1): 153, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28666427

RESUMO

BACKGROUND: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old. METHODS/DESIGN: Participants are 163 children (M age [SD] = 8.44 [0.34] years, 76 males) and their mothers (M age [SD] = 40.34 [5.43] years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017. DISCUSSION: This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.


Assuntos
Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil , Transtornos Mentais/etiologia , Relações Pais-Filho , Poder Familiar/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Criança , Protocolos Clínicos , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/psicologia , Fatores de Risco
6.
J Colloid Interface Sci ; 488: 258-268, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27837716

RESUMO

In this study, we developed iron oxide based magnetic nanoparticles (MNPs) by precipitation of iron salts in the presence of ammonia and created four different formulations: without functionality (plain MNPs, no coating), with ß-cyclodextrin (MNPs+ß-CD) or pluronic 127 polymer (MNPs+F-127), and both ß-cyclodextrin and pluronic 127 polymer (MNPs+ß-CD-F-127) functionality for its efficient use in mucosal delivery. We studied the interaction and/or binding behavior of these MNPs formulations with porcine stomach mucin using steady-state fluorescence spectroscopy, and then quantified the bound mucin from absorption studies. Toxicity of these MNPs against cervical cancer cells and red blood cells was evaluated. Ex-vivo studies were performed using freshly collected gastrointestinal, ovarian, pancreas and colon organ tissues of pig to evaluate binding and uptake phenomenon of MNPs. Transport studies of these MNPs in mucin was evaluated using Boyden's chamber assay. All these studies together suggest that the MNPs+ß-CD-F-127 formulation was strongly interacted with mucin and interestingly transported through mucin compared to other MNPs formulations. Hence, MNPs+ß-CD-F-127 formulation could be a good candidate for the mucoadhesive biopharmaceuticals and drug delivery system.


Assuntos
Portadores de Fármacos/metabolismo , Nanopartículas de Magnetita/química , Mucinas/metabolismo , Poloxâmero/química , beta-Ciclodextrinas/química , Amônia/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colo/metabolismo , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Feminino , Compostos Férricos/química , Mucosa Gástrica/metabolismo , Humanos , Nanopartículas de Magnetita/ultraestrutura , Ovário/metabolismo , Pâncreas/metabolismo , Espectrometria de Fluorescência , Suínos
8.
Transl Psychiatry ; 6(6): e841, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27327256

RESUMO

Multiple cross-sectional imaging studies have identified structural abnormalities in prefrontal, temporal and limbic regions related to conduct problems (CPs). However, the relationship between development of such neurobiological deficits and developmental pathways of CPs has remained unclear. The current study investigated distinct trajectories of CP and related trajectories of cortical thickness within a community-based sample of adolescents (n=239), age range 12-19, to address this gap. Three trajectory classes were revealed using latent class growth analyses (LCGAs), comprising a 'desisting' CP group, an 'intermediate' CP group and a 'stable low' CP group. Structural magnetic resonance imaging (MRI) scans were collected with a subgroup of 171 adolescents at three waves throughout adolescence (ages 12, 16 and 19). Generalized estimating equation (GEE) analysis-comparing longitudinal changes in cortical thickness and subcortical volume between CP groups for several regions of interest (ROIs)-showed that these CP groups had differential trajectories of cortical thickness in the dorsolateral prefrontal cortex (dl-PFC), and the anterior cingulate cortex (ACC), and volume of the hippocampus. Adolescents in the desisting CP group showed an attenuation of the typical pattern of cortical thinning as present in the intermediate and stable low CP groups, in addition to an exaggeration of the typical pattern of hippocampal volume increase. These findings suggest that a deviant cortical thickness trajectory was related to a desisting CP pathway across adolescence. Such deviant neurodevelopmental growth trajectories may act as an underlying mechanism for developmental CP pathways, and possibly distinguish desisting antisocial adolescents.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Transtorno da Conduta/diagnóstico por imagem , Transtorno da Conduta/patologia , Imageamento por Ressonância Magnética , Adolescente , Transtorno da Personalidade Antissocial/diagnóstico por imagem , Transtorno da Personalidade Antissocial/patologia , Transtorno da Personalidade Antissocial/psicologia , Mapeamento Encefálico , Criança , Transtorno da Conduta/psicologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Controle Interno-Externo , Estudos Longitudinais , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Tamanho do Órgão , Inquéritos e Questionários
9.
J Neurol Sci ; 364: 167-76, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-27084239

RESUMO

Autism spectrum disorders denote a series of lifelong neurodevelopmental conditions characterized by an impaired social communication profile and often repetitive, stereotyped behavior. Recent years have seen the complex genetic architecture of the disease being progressively unraveled with advancements in gene finding technology and next generation sequencing methods. However, a complete elucidation of the molecular mechanisms behind autism is necessary for potential diagnostic and therapeutic applications. A multidisciplinary approach should be adopted where the focus is not only on the 'genetics' of autism but also on the combinational roles of epigenetics, transcriptomics, immune system disruption and environmental factors that could all influence the etiopathogenesis of the disease. ASD is a clinically heterogeneous disorder with great genetic complexity; only through an integrated multidimensional effort can modern autism research progress further.


Assuntos
Transtorno do Espectro Autista/genética , Meio Ambiente , Genoma , Transcriptoma/fisiologia , Aberrações Cromossômicas , Bases de Dados Factuais/estatística & dados numéricos , Humanos
10.
Mol Neurobiol ; 53(4): 2579-93, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26081149

RESUMO

Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain.


Assuntos
Isquemia Encefálica/patologia , Precondicionamento Isquêmico , Animais , Isquemia Encefálica/genética , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Epigênese Genética , Humanos
11.
Dev Cogn Neurosci ; 14: 62-70, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26209810

RESUMO

Adolescence is a critical period of development, in which the increasing social and cognitive demands of independence need to be met by enhanced self-regulatory abilities. The cultivation of mindfulness has been associated with improved self-regulation in adult populations, and it is theorized that one neurodevelopmental mechanism that supports this capacity is the development of the prefrontal cortex. The current study examined the neurodevelopmental mechanisms associated with dispositional mindfulness in adolescence. Using a longitudinal within-persons design, 82 participants underwent structural magnetic resonance imaging (MRI) assessments at approximately ages 16 and 19, and also completed self-reported measurements of mindfulness at age 19. It was hypothesized that adolescents who demonstrated greater thinning of frontal cortical regions between the age of 16 and 19 would exhibit higher dispositional mindfulness levels at age 19. Results indicated that, contrary to predictions, adolescents with higher levels of mindfulness demonstrated less thinning in the left anterior insula. By contrast, higher IQ was associated with greater thinning of the right caudal middle frontal and right superior frontal regions. The involvement of insula development in mindfulness is consistent with a direct role for this structure in managing self-regulation, and in doing so concords with recent models of self-referential interoceptive awareness.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Atenção Plena , Adolescente , Conscientização/fisiologia , Criança , Feminino , Humanos , Testes de Inteligência , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/fisiologia , Autocontrole , Temperamento/fisiologia , Adulto Jovem
12.
Int J Cardiol ; 187: 519-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25846664

RESUMO

INTRODUCTION: India carries the greatest burden of global non-communicable diseases (NCDs). Poverty is strongly associated with NCDs but there are few prevalence studies which have measured poverty in India, particularly in rural settings. METHODS: In Kerala, India, a population of 113,462 individuals was identified. The "Epidemiology of Non-communicable Diseases in Rural Areas" (ENDIRA) study was conducted via ASHAs (Accredited Social Health Activists). Standardised questionnaires were used in household interviews of individuals ≥18years during 2012 to gather sociodemographic, lifestyle and medical data for this population. The Government of Kerala definition of "the poverty line" was used. The association between below poverty line (BPL) status, NCDs and risk factors was analysed in multivariable regression models. RESULTS: 84,456 adults were included in the analyses (25.4% below the poverty line). The prevalence of NCDs was relatively common: myocardial infarction (MI) 1.4%, stroke 0.3%, respiratory diseases 5.0%, and cancer 1.1%. BPL status was not associated with age (p=0.96) or gender (p=0.26). Compared with those above the poverty line (APL), the BPL group was less likely to have diabetes, hypertension or dyslipidaemia (p<0.0001), and more likely to smoke (p<0.0001). Compared with APL, BPL was associated with stroke (OR 1.33, 1.04-1.69; p=0.02) and respiratory disease (OR 1.23, 1.15-1.32; p<0.0001) in multivariable analyses, but not MI or cancer. CONCLUSIONS: In rural Kerala, BPL status was associated with stroke and respiratory diseases, but not with MI and cancer although it was associated with smoking status, compared with above poverty line status.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Pobreza/estatística & dados numéricos , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários
13.
Indian J Cancer ; 52(4): 690-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26960521

RESUMO

INTRODUCTION: Tobacco use among school children is becoming a serious problem in developing countries. The early age of initiation underscores the urgent need to intervene and protect this vulnerable group from becoming victims of this addiction. AIM: To assess the knowledge, attitudes, and practices about tobacco use among 13-15 year old school children of Bangalore City. MATERIALS AND METHODS: A cross-sectional study was designed and data on tobacco usage was collected from 1288 students aged 13-15 years studying in six government and private schools of Bangalore using a self-administered closed ended questionnaire. Data was analyzed using SPSS 15.0 and descriptive statistics was applied. Chi-square tests were used to determine the significant differences in the variables of interest. RESULTS: Out of 1288 children, 1281 (99.5%) children had heard about tobacco and 1162 (90.2%) students knew the harmful effects of tobacco. Only 28 (2.2%) had used tobacco products. Peer pressure was the main reason for tobacco use among children and age was not a barrier in buying tobacco products. Television (58%) was the main source of information for tobacco products followed by newspapers (26%) and movies (16%). CONCLUSION: It is encouraging to find that majority of the 13-15 year old children surveyed in the present study did not use tobacco and were aware of the health risks associated with tobacco use. This calls for the school authorities to be included in stricter implementation and monitoring of the implementation of legislation. Regular and systematic education programs catering to teachers, children, and also their parents should be undertaken.


Assuntos
Uso de Tabaco/epidemiologia , Adolescente , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Inquéritos e Questionários
14.
Medchemcomm ; 4(7): 1073-1078, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23956835

RESUMO

A new library of small molecules with structural features resembling combretastatin analogs was synthesized and evaluated for anticancer activity against a panel of 60 human cancer cell lines. Three novel acrylonitrile analogs (5, 6 and 13) caused a significant reduction in cell growth in almost all the cell lines examined, with GI50 values generally in the range 10-100 nM. Based on the structural characteristics of similar drugs, we hypothesized that the cytotoxic activity was likely due to interaction with tubulin. Furthermore, these compounds appeared to overcome cell-associated P-glycoprotein (P-gp)-mediated resistance, since they were equipotent in inhibiting OVCAR8 and NCI/ADR-Res cell growth. Given that antitubulin drugs are among the most effective agents for the treatment of advanced prostate cancer we sought to validate the results from the 60 cell panel by studying the representative analog 6 utilizing prostate cancer cell lines, as well as exploring the molecular mechanism of the cytotoxic action of this analog.

15.
Acta Crystallogr C ; 68(Pt 11): o436-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23124457

RESUMO

The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a diastereomerically pure form by the reaction of oxycodone with 3-chloroperbenzoic acid and subsequent crystallization of the product from chloroform. The crystal packing shows that the molecule exhibits intramolecular O-H···O [D···A = 2.482 (2) Å] hydrogen bonding. In addition, there are weak intermolecular C-H...O interactions which, along with van der Waals forces, stabilize the structure. The new chiral center at the 17-position is demonstrated to be R.


Assuntos
Clorobenzoatos/química , Oxicodona/química , Oxicodona/síntese química , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura Molecular
16.
Acta Crystallogr C ; 68(Pt 10): o405-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23007543

RESUMO

In the title compounds, C(10)H(8)N(2)O(2), (I), and C(12)H(12)N(2)O(2), (II), the two carbonyl groups are oriented with torsion angles of -149.3 (3) and -88.55 (15)°, respectively. The single-bond distances linking the two carbonyl groups are 1.528 (4) and 1.5298 (17) Å, respectively. In (I), the molecules are linked by an elaborate system of N-H···O hydrogen bonds, which form adjacent R(2)(2)(8) and R(4)(2)(8) ring motifs to generate a ladder-like construct. Adjacent ladders are further linked by N-H···O hydrogen bonds to build a three-dimensional network. The hydrogen bonding in (II) is far simpler, consisting of helical chains of N-H···O-linked molecules that follow the 2(1) screw of the b axis. It is the presence of an elaborate hydrogen-bonding system in the crystal structure of (I) that leads to the different torsion angle for the orientation of the two adjacent carbonyl groups from that in (II).


Assuntos
Acetamidas/química , Indóis/química , Cristalografia por Raios X , Ligação de Hidrogênio , Conformação Molecular , Estrutura Molecular
17.
Dent Res J (Isfahan) ; 9(6): 710-4, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23559946

RESUMO

BACKGROUND: Dental caries among preschool children is still a major public health problem in many developing countries including India. Hence the aim of the present study was to find out the prevalence of Early Childhood Caries among 3-5 year old pre-schoolers in schools of Marathahalli, Bangalore. MATERIALS AND METHODS: A cross sectional study was conducted on 717 pre-schoolers in 6 schools of Marathahalli. Clinical examination was performed and deft index was recorded using Gruebell's criteria. Early Childhood Caries was diagnosed using Early Childhood Caries Diagnostic Criteria, consistent with the NIDCR workshop statement. Data was analysed using SPSS 15.0 and descriptive statistics was applied. Chi-square test was used to find out the significant differences. The level of significance was taken at P value < 0.05. RESULTS: Prevalence of early childhood caries was 40% with a mean deft of 1.89 (+3.3) and Significant Caries Index score was 5.51. 44.8% of 3 year old had Early Childhood Caries, 35% of 4 year old children and 41% of 5 year old had Early Childhood Caries. Almost, all of deft was due to untreated caries. CONCLUSION: The results of the present study calls for a need to focus on pre-schoolers' oral health and parental education for prevention and early detection of Early Childhood Caries. A high Significant Caries Index in this study population indicates a more targeted approach for high risk pre-schoolers.

18.
FASEB J ; 23(9): 2986-95, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19395476

RESUMO

There is a need for novel strategies that target tumor vasculature, specifically those that synergize with cytotoxic therapy, in order to overcome resistance that can develop with current therapeutics. A chemistry-driven drug discovery screen was employed to identify novel compounds that inhibit endothelial cell tubule formation. Cell-based phenotypic screening revealed that noncytotoxic concentrations of (Z)-(+/-)-2-(1-benzenesulfonylindol-3-ylmethylene)-1-azabicyclo[2. 2.2]octan-3-ol (analog I) and (Z)-(+/-)-2-(1-benzylindol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol (analog II) inhibited endothelial cell migration and the ability to form capillary-like structures in Matrigel by > or =70%. The ability to undergo neoangiogenesis, as measured in a window-chamber model, was also inhibited by 70%. Screening of biochemical pathways revealed that analog II inhibited the enzyme ENOX1 (EC(50) = 10 microM). Retroviral-mediated shRNA suppression of endothelial ENOX1 expression inhibited cell migration and tubule formation, recapitulating the effects observed with the small-molecule analogs. Genetic or chemical suppression of ENOX1 significantly increased radiation-mediated Caspase3-activated apoptosis, coincident with suppression of p70S6K1 phosphorylation. Administration of analog II prior to fractionated X-irradiation significantly diminished the number and density of tumor microvessels, as well as delayed syngeneic and xenograft tumor growth compared to results obtained with radiation alone. Analysis of necropsies suggests that the analog was well tolerated. These results suggest that targeting ENOX1 activity represents a novel therapeutic strategy for enhancing the radiation response of tumors.


Assuntos
Endotélio Vascular/citologia , Neovascularização Patológica/tratamento farmacológico , Proteína Dissulfeto Redutase (Glutationa)/antagonistas & inibidores , Quinuclidinas/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Movimento Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Humanos , Indóis , Proteínas de Membrana/antagonistas & inibidores , Neoplasias/irrigação sanguínea , Neoplasias/terapia , Neovascularização Patológica/radioterapia , Quinuclidinas/uso terapêutico
19.
J Enzyme Inhib Med Chem ; 24(1): 117-24, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18629678

RESUMO

A series of hydrazone and 3-nitrovinyl analogs of indole-3-carboxaldehydes and related compounds were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H37R(V) in BACTEC 12B medium using the Microplate Alamar Blue Assay (MABA). Several compounds showed inhibitory activity against M. tuberculosis in primary screening assays at a concentration of 6.25 microg/mL; subsequent dose-response studies indicated that the most active compounds, 3d, 3e & 8b, had IC(50) values of 5.96, 5.4 & 1.6 microg/mL, respectively. These compounds represent potential leads for the further development of novel antitubercular agents.


Assuntos
Antituberculosos/síntese química , Hidrazonas/síntese química , Compostos de Vinila/síntese química , Aldeídos/química , Relação Dose-Resposta a Droga , Hidrazonas/farmacologia , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Compostos de Vinila/farmacologia
20.
Acta Crystallogr C ; 63(Pt 12): o743-5, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18057629

RESUMO

The title compounds, C20H17NO3S, (I), and C19H15NO2S, (II), were prepared by the reaction of benzo[b]thiophene-2-carbaldehyde with (3,4,5-trimethoxyphenyl)acetonitrile and (3,4-dimethoxyphenyl)acetonitrile, respectively, in the presence of methanolic potassium hydroxide. In (I), the C=C bond linking the benzo[b]thiophene and the 3,4,5-trimethoxyphenyl units has E geometry, with dihedral angles between the plane of the bridging unit and the planes of the two adjacent ring systems of 5.2 (3) and 13.1 (2) degrees, respectively. However, in (II), the C=C bond has Z geometry, with dihedral angles between the plane of the bridging unit and the planes of the adjacent benzo[b]thiophene and 3,4-dimethoxyphenyl units of 4.84 (17) and 76.09 (7) degrees, respectively. There are no significant intermolecular hydrogen-bonding interactions in the packing of (I) and (II). The packing is essentially stabilized via van der Waals forces.


Assuntos
Acetonitrilas/química , Acrilonitrila/análogos & derivados , Tiofenos/química , Acrilonitrila/síntese química , Acrilonitrila/química , Cristalografia por Raios X , Estrutura Molecular , Tiofenos/síntese química
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