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BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).
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Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Placebos , Resultado do Tratamento , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Painless dentistry, minimal intervention and thus giving comfort, relief and solace and instill positive attitude toward dental treatments, are some of the factors justifying the specialty of pediatric dentistry. Thus, this in vitro study was undertaken to compare the efficacy of a new chemomechanical caries removal agent, Papacarie (Formula and Acao), with conventional slow-speed rotary instrument (bur). Papacarie is a new formulation and has the main active ingredient papain, an endoprotein with bactericidal, bacteriostatic and anti-inflammatory actions. Twenty extracted human molar teeth with deep dentine caries and no enamel coverage were selected for the study. After the preparation of the teeth and removal of the caries with the respective methods, they were decalcified, dehydrated and embedded in paraffin blocks for histologic studies. Serial sections of 5 mum thickness were examined for the presence of bacteria under light microscope. Though complete removal of caries was achieved significantly in both the methods, there was less marked destruction of dentinal tubules in chemomechanical caries removal method by Papacarie. Thus, Papacarie is recommended as an efficient, easy to perform, comfortable and less destructive solution for the patient seeking an alternative to the conventional method.
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Tratamento Dentário Restaurador sem Trauma/métodos , Preparo da Cavidade Dentária/métodos , Papaína , Cárie Dentária/terapia , Preparo da Cavidade Dentária/instrumentação , Humanos , Dente Molar , Fatores de TempoRESUMO
BACKGROUND: Dental caries is defined as an infectious disease of microbial origin which is related to every specialty of dentistry in one or the other way. Genetic susceptibility to dental caries is dependent on certain factors, which if evaluated, can help in estimating disease situation prematurely. The present study was done to estimate dermatoglyphic dependence of dental caries and its relation with salivary bacteria levels, primarily Streptococcus mutans. AIMS: To determine if there is any significant correlation between salivary bacteria interactions, dermatoglyphics, and dental caries. SETTINGS AND DESIGN: In the present study, 90 subjects were evaluated for dermatoglyphics in conjunction with bacteria levels. METHODS AND MATERIALS: Dermatoglyphic interpretation was done using stamp-pad method and S. mutans levels were estimated by microbial culture of salivary samples collected. STATISTICAL ANALYSIS: Z-test (standard normal variate, proportion) was used to analyze dermatoglyphic patterns and bacteria levels. RESULTS AND CONCLUSIONS: 1. Subject group had a decreased frequency of loops, whereas control group had an increased frequency of loops on all palmar digits. 2. Subject group had high S. mutans growth, whereas control group had low S. mutans growth. Subject group had positive correlation with loops and S. mutans growth likened to control group that had negative correlation with both.
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Cárie Dentária/genética , Dermatoglifia , Saliva/microbiologia , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Índice CPO , Predisposição Genética para Doença , Humanos , Streptococcus mutans/isolamento & purificaçãoRESUMO
Amine-functionalised framework NH2-MIL-101(Al) was synthesized using a solvothermal and microwave method and characterized by PXRD, FT-IR, TGA, SEM-EDX, and BET surface area analysis. The desolvated framework, in the presence of co-catalyst tetrabutylammonium bromide (TBAB), acted as an excellent heterogeneous catalyst for the solvent-free cycloaddition of carbon dioxide (CO2) with epoxides, affording five-membered cyclic carbonates. Using styrene oxide, the NH2-MIL-101(Al)/TBAB system showed more than 99% conversion, affording 96% yield and 99% selectivity with a turn over frequency of 23.5 h-1. This validated the synergistic effect of the quaternary ammonium salt during CO2 cycloaddition. The catalyst could be recycled at least five times without a noticeable loss in activity, while leaching test showed no leached Al3+ ions throughout the reaction. Thorough analysis of the reaction parameters showed that the optimum conditions for obtaining the maximum yield and highest selectivity were 120 °C and 18 bar of CO2 for 6 h. The outstanding conversion and selectivity were maintained for a range of aliphatic and aromatic epoxides, corroborating the duel benefit of the micro-mesoporous system with amine functionality, which offered easy access for reactant molecules with diverse sizes, and provided inspiration for future CO2 cycloaddition catalytic systems. We also propose a rationalized mechanism for the cycloaddition reaction mediated by NH2-MIL-101(Al) and TBAB based on literature precedent and experimental outcome.
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BACKGROUND: The metabolic syndrome is a cluster of atherothrombotic risk factors that are commonly associated with insulin resistance. OBJECTIVES: The aim of this study was to investigate ethnic differences in insulin resistance and non-traditional cardiovascular risk factors in relation to the International Diabetes Federation (IDF) definition of the metabolic syndrome. PATIENTS AND METHODS: A total of 245 healthy South Asians and 245 age- and sex-matched Caucasians were studied. C-reactive protein (CRP), complement C3, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated from fasting plasma glucose and insulin levels. RESULTS: Fifty Caucasian (20%) and 95 (39%) South Asian subjects had the metabolic syndrome as defined by the IDF. In South Asian subjects, HOMA-IR, CRP, C3, PAI-1 and t-PA were significantly higher in subjects with the metabolic syndrome. In contrast, in Caucasian individuals there was no difference in HOMA-IR or C3 levels and only CRP, PAI-1 and t-PA were higher in subjects with the metabolic syndrome. In a logistic regression model, plasma levels of CRP and PAI-1 were independent predictors of the metabolic syndrome in Caucasians, whereas plasma levels of C3 and t-PA as well as HOMA-IR were independent predictors of the metabolic syndrome in South Asian subjects. CONCLUSIONS: In the cohort of individuals studied, the IDF definition of the metabolic syndrome was associated with insulin resistance in the South Asian but not the Caucasian population. This work also showed ethnic differences in non-traditional cardiovascular risk factors in the presence of the metabolic syndrome.
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Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Adulto , Povo Asiático , Proteína C-Reativa/biossíntese , Doenças Cardiovasculares/complicações , Estudos de Coortes , Complemento C3/biossíntese , Feminino , Humanos , Resistência à Insulina , Masculino , Inibidor 1 de Ativador de Plasminogênio/sangue , Fatores de Risco , Ativador de Plasminogênio Tecidual/biossíntese , População BrancaRESUMO
The effect of the Escherichia coli single-stranded DNA binding (SSB) protein on the stability of complexes of E. coli RecA protein with single-stranded DNA has been investigated through direct DNA binding experiments. The effect of each protein on the binding of the other to single-stranded DNA, and the effect of SSB protein on the transfer rate of RecA protein from one single-stranded DNA molecule to another, were studied. The binding of SSB protein and RecA protein to single-stranded phage M13 DNA is found to be competitive and, therefore, mutually exclusive. In the absence of a nucleotide cofactor, SSB protein binds more tightly to single-stranded DNA than does RecA protein, whereas in the presence of ATP-gamma-S, RecA protein binds more tightly than SSB protein. In the presence of ATP, an intermediate result is obtained that depends on the type of DNA used, the temperature, and the magnesium ion concentration. When complexes of RecA protein, SSB protein and single-stranded M13 DNA are formed under conditions of slight molar excess of single-stranded DNA, no effect of RecA protein on the equilibrium stability of the SSB protein-single-stranded DNA complex is observed. Under similar conditions, SSB protein has no observed effect on the stability of the RecA protein-etheno M13 DNA complex. Finally, measurements of the rate of RecA protein transfer from RecA protein-single-stranded DNA complexes to competing single-stranded DNA show that there is no kinetic stabilization of the RecA protein-etheno M13 DNA complex by SSB protein, but that a tenfold stabilization is observed when single-stranded M13 DNA is used to form the complex. However, this apparent stabilizing effect of SSB protein can be mimicked by pre-incubation of the RecA protein-single-stranded M13 DNA complex in low magnesium ion concentration, suggesting that this effect of SSB protein is indirect and is mediated through changes in the secondary structure of the DNA. Since no direct effect of SSB protein is observed on either the equilibrium or dissociation properties of the RecA protein-single-stranded DNA complex, it is concluded that the likely effect of SSB protein in the strand assimilation reaction is on a slow step in the association of RecA protein with single-stranded DNA. Direct evidence for this conclusion is presented in the accompanying paper.
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Proteínas de Bactérias/metabolismo , Bacteriófagos/metabolismo , DNA de Cadeia Simples/metabolismo , DNA Viral/metabolismo , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/metabolismo , Recombinases Rec A/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Ligação Competitiva , Cinética , Magnésio/metabolismo , TemperaturaRESUMO
A simple visual test was used to measure how much Listing's plane rotates as a function of the vergence angle. This test measured the elevation-dependent torsional disparity of horizontal and vertical lines during three tasks: vergence on a near target, vergence through prisms that remained fixed, and through prisms that rotated with eye elevation. Consistent with our previous search-coil measurements, the results here suggest that the angle between the Listing's planes of the two eyes is somewhat less than the vergence angle.
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Convergência Ocular/fisiologia , Fixação Ocular , Humanos , Masculino , Matemática , Rotação , Disparidade Visual/fisiologia , Visão BinocularRESUMO
The synoptophore was used to measure torsional interocular disparity. This, in turn, was used to compute how much the angle between the Listing's plane (LP) of the two eyes changes as a function of the vergence angle. The ratio of these two angles was defined as G. We measured G in normals and in patients suffering from intermittent horizontal strabismus. Consistent with previous search-coil experiments and with our previous visual test measures, the results using the synoptophore suggest that, for normals, G is less than 1. In the patient group the mean G was similar in magnitude but more variable. The variations in G did not appear to be related to the patient's measurement of ocular deviation. This result suggests that the vergence-related rotation of LP in these patients may be related to other factors besides the effort required to fuse the lines of sight.
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Convergência Ocular/fisiologia , Estrabismo/fisiopatologia , Humanos , Matemática , Rotação , Disparidade VisualRESUMO
The present investigation was aimed at determining the spectrum of activity of the methanolic extract of Clitoria ternatea (CT) on the CNS. The CT was studied for its effect on cognitive behavior, anxiety, depression, stress and convulsions induced by pentylenetetrazol (PTZ) and maximum electroshock (MES). To explain these effects, the effect of CT was also studied on behavior mediated by dopamine (DA), noradrenaline, serotonin and acetylcholine. The extract decreased time required to occupy the central platform (transfer latency, TL) in the elevated plus maze (EPM) and increased discrimination index in the object recognition test, indicating nootropic activity. The extract was more active in the object recognition test than in the EPM. The extract increased occupancy in the open arm of EPM by 160% and in the lit box of the light/dark exploration test by 157%, indicating its anxiolytic activity. It decreased the duration of immobility in tail suspension test (suggesting its antidepressant activity), reduced stress-induced ulcers and reduced the convulsing action of PTZ and MES. The extract exhibited tendency to reduce the intensity of behavior mediated via serotonin and acetylcholine. The effect on DA- and noradrenaline-mediated behavior was not significant. In conclusion, the extract was found to possess nootropic, anxiolytic, antidepressant, anticonvulsant and antistress activity. Further studies are necessary to isolate the active principle responsible for the activities and to understand its mode of action.
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Fármacos do Sistema Nervoso Central/uso terapêutico , Clitoria , Transtornos Mentais/tratamento farmacológico , Componentes Aéreos da Planta , Animais , Catalepsia/induzido quimicamente , Catalepsia/tratamento farmacológico , Fármacos do Sistema Nervoso Central/isolamento & purificação , Fármacos do Sistema Nervoso Central/farmacologia , Hipotermia/induzido quimicamente , Hipotermia/tratamento farmacológico , Masculino , Transtornos Mentais/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , Fitoterapia/métodos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológicoRESUMO
The effect of saponin containing n-butanolic fraction (BF) extracted from dried leaves of Albizzia lebbeck on learning and memory was studied in albino mice using passive shock avoidance paradigm and the elevated plus maze. Significant improvement was observed in the retention ability of the normal and amnesic mice as compared to their respective controls. We have also studied the effects of BF on the behavior influenced by serotonin (5-HT), noradrenaline and dopamine. The brain levels of serotonin, gamma-aminobutyric acid (GABA) and dopamine were also estimated to correlate the behavior with neurotransmitter levels. The brain concentrations of GABA and dopamine were decreased, whereas the 5-HT level was increased. The data indicate the involvement of monoamine neurotransmitters in the nootropic action of BF of A. lebbeck.
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Albizzia/química , Aprendizagem/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Catalepsia/induzido quimicamente , Clonidina/farmacologia , Depressão/induzido quimicamente , Dopamina/análise , Relação Dose-Resposta a Droga , Feminino , Haloperidol/farmacologia , Hipotermia/induzido quimicamente , Lítio/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Norepinefrina/análise , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Saponinas/administração & dosagem , Saponinas/toxicidade , Serotonina/análiseRESUMO
Recent advances in cancer research highlighted the importance of target-specific drug discovery. In view of these advances, the most important mechanism in tumour growth is its ability to stimulate the formation of blood capillaries around itself called tumour-driven angiogenesis. Hence targeting the angiogenesis, inhibits the growth of blood vessels around it and responsible for death of the tumour due to starvation and accumulation of toxic waste. The therapy, thus, indirectly cytotoxic to the tumour cells by targeting newly developing blood vessels. In this review, we summarised the various antiangiogenic agents with their clinical uses and current status.
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Nonsteroidal antiinflammatory drugs have been widely used for the management of inflammation, pain and nociception. Gastric intolerance caused by most of the nonsteroidal antiinflammatory drugs used today restricts their use. Several approaches have been proposed to modify the parent nonsteroidal antiinflammatory drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach is one of such approaches. In the present work three nonsteroidal antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs were screened for their analgesic and antiinflammatory activity using Eddy's hot plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method, respectively. These prodrugs were also evaluated for their ulcerogenic potential. All synthesized prodrugs were found to be less ulcerogenic than their parent nonsteroidal antiinflammatory drugs and showed better activity profile in terms of analgesic and antiinflammatory activity as compared to their respective parent drugs.
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Synthesis of 1,3,4-oxadiazole derivatives of diclofenac and mefenamic acid are described. The target compounds 5-[2-(2,6-dichloroanilino)benzyl]-2-aryl-1,3,4-oxadiazole (3a-3e) and 5-[2-(2,3-dimethylanilino)phenyl]-2-(aryl)-1,3,4-oxadiazole (6a-6e) were obtained by treating 2 and 5 with various aromatic acids using POCl(3) as dehydrating agent. They were purified and characterized by IR, (1)H-NMR and elemental analysis. These compounds were further subjected to antiinflammatory, analgesic and acute ulcerogenic activity. Compound 3c and 6d exhibited good antiinflammatory activity and compounds 3c, 3e, 6c, 6d, 6e were found to be non ulcerogenic.
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Spontaneous resolution of intracranial aneurysms is a rare phenomenon. We describe two cases of ruptured distal middle cerebral artery branch aneurysms associated with initial neurological deficit. Follow-up angiography showed complete resolution of the aneurysms.
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BACKGROUND: Achyranthes Aspera Linn., known as Chirchira (Hindi), Agadha (Marathi) is an indigenous herb found in India. The herb has been reported to have variety of activities like antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic and cardiotonic, analgesic, anti-inflammatory, hypnotic, antifungal and antibacterial activity. It has been also reported to have central anti-nociceptive activity in thermal induced pain methods in our earlier studies. We wanted to study its neuropharmacological effects, which may throw light on understanding the underlying mechanism for its central activity. PURPOSE: The present study was designed to evaluate CNS depressant and behavioral effects of A. Aspera extract and to study the phytochemical responsible for these activities with possible mode of action. METHODS: The effects on behavioral activity was studied using open field test (OFT). The extract was given intraperitoneally at a dose of 400 mg/kg. Diazepam (2mg/kg body weight i.p.) was used as standard. Data was analyzed by ANOVA test followed by Dunnett's test. All the results were expressed as Mean (±SEM). P <0.05 was considered significant. RESULTS: Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine) and steroids as major constituents. The result of the study demonstrated that ethanol extract of A. Aspera (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation and showed antianxiety activity. CONCLUSIONS: Ethanols extract of A. Aspera exhibit CNS depressant action and significant anxiolytic activity comparable to diazepam.
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Histone Deacetylases (HDACs) enzymes are critical in regulating gene expression and transcription. They also play a fundamental role in regulating cellular activities such as cell proliferation, survival and differentiation. Inhibition of HDACs has generated many fascinating results including a new strategy in human cancer therapy. HDAC Inhibitors (HDACIs) like SAHA, TSA are emerging as new promising drugs for various anti-inflammatory and CNS-disorders. This review, along with chemical classification, emphasizes on the therapeutic potential of various HDACIs against different diseases.
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Inibidores de Histona Desacetilases/química , Acilação , Animais , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/metabolismo , Inibidores de Histona Desacetilases/uso terapêutico , Histonas/química , Histonas/metabolismo , Humanos , Relação Estrutura-AtividadeRESUMO
Diabetic neuropathy (DN) is a multifactor complication of diabetes. It is a late finding in type 1 diabetes, but can be an early finding in type 2 diabetes. The cause of DN is still unclear and, like other complications of diabetes, it may be the result of various pathological conditions. Animal models and biomarkers of DN have been extensively used in neuropathic research. The most useful model of DN should exhibit the key feature present in human pathology. Diabetic rodents show behavioral, functional, structural and molecular biomarkers and they are widely used as models to investigate the etiology of DN as well as to screen the efficacy of the potential therapeutic interventions. We have reviewed the different animal models and biomarkers of neuropathy in diabetic rodents of either type 1 or type 2 diabetes.