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1.
Phys Rev Lett ; 124(6): 063601, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32109106

RESUMO

We report on the realization of long-range Ising interactions in a cold gas of cesium atoms by Rydberg dressing. The interactions are enhanced by coupling to Rydberg states in the vicinity of a Förster resonance. We characterize the interactions by measuring the mean-field shift of the clock transition via Ramsey spectroscopy, observing one-axis twisting dynamics. We furthermore emulate a transverse-field Ising model by periodic application of a microwave field and detect dynamical signatures of the paramagnetic-ferromagnetic phase transition. Our results highlight the power of optical addressing for achieving local and dynamical control of interactions, enabling prospects ranging from investigating Floquet quantum criticality to producing tunable-range spin squeezing.

2.
Molecules ; 24(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141987

RESUMO

Overcoming the disadvantages of low transmission and broad peak bandwidth of previously reported plasmonic color filters, a high-efficiency multispectral plasmonic color filter is theoretically proposed with two cascaded ultrathin metallic nanogratings separated by two heterogeneous dielectric layers, and its optical properties are theoretically investigated using the finite-difference time-domain method. The transmission spectrum presents three near-unity peak bands accompanied with three near-null dip bands adjacent around them. Both transmission efficiencies of above 90% and ultranarrow peak bandwidth of 20 nm are achieved in the visible regime. The peak band positions can be flexibly tailored by varying the structural parameters. The filter selects the visible color with high signal noise ratio at the peak bands. The outstanding spectral properties of this filter indicate significant improvement for the high-accuracy color filtering and multispectral imaging applications. The simulated near-field electromagnetic distributions suggest that the excitation of the hybrid antisymmetric surface plasmon polariton (SPP) leaky mode and metal-insulator-metal waveguide modes are responsible for the peak transmission bands, while the formation of the hybrid SPP bound modes confined on the bottom nanograting makes the dip transmission bands, all of which are the consequence of the plasmonic hybridization between the two neighboring metallic nanogratings.


Assuntos
Nanopartículas/química , Fenômenos Ópticos , Campos Eletromagnéticos
3.
Dis Esophagus ; 31(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800269

RESUMO

Evaluation of dysphagia typically starts with esophagogastroduodenoscopy (EGD); further testing is pursued if this is negative. When no mucosal, structural, or motor esophageal disorders are identified with persisting symptoms, functional dysphagia is considered. We evaluated outcomes in patients undergoing EGD for dysphagia, and estimated prevalence of functional dysphagia. The endoscopy database at single tertiary care center was interrogated to identify EGDs performed for an indication of 'dysphagia' over a 12-month period (2008-09). Electronic medical records were reviewed over the next 8 years to assess if an etiology was identified. Data were analyzed to assess the diagnostic yield of endoscopy and subsequent tests in the evaluation of dysphagia. Of 5486 EGDs, 822 (15.0%) were performed for dysphagia in 694 patients (58.4 ± 0.6 year, range: 18-95 year, 55.8% female). Of these, 529 (76.2%) had EGD findings that explained dysphagia; another 22 (3.2%) had findings on histopathology. Of the remainder 143 patients (20.6%) with normal index EGD, 38 (26.6%) patients underwent barium esophagram with 15 (39.5%) having abnormal studies. 19 patients (13.3%) underwent esophageal high resolution manometry with 12 (63.2%) being abnormal, and 7 had a mechanism for dysphagia on alternate testing. A repeat EGD was abnormal in 6 patients, while 45 patients were lost to follow-up. 42 patients had complete resolution of symptoms despite normal endoscopy, of which 30 were treated empirically with a proton pump inhibitor (PPI). Only 16 patients had no findings on evaluation, and had continued dysphagia symptoms, representing true functional dysphagia in 2.3% of all dysphagia patients and 11.2% of patients with normal EGD. Endoscopy remains the test with the highest yield (over 75%) for a diagnosis in patients presenting with dysphagia; secondary tests are useful when endoscopy does not provide a diagnosis. Benign strictures and GERD-related etiologies are leading causes; PPI therapy is useful even when testing is negative. Functional dysphagia is extremely rare, accounting for <2.5% of all dysphagia.


Assuntos
Transtornos de Deglutição/diagnóstico , Endoscopia do Sistema Digestório/estatística & dados numéricos , Manometria/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
7.
Mol Hum Reprod ; 21(8): 672-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26002969

RESUMO

Both term and preterm parturition are characterized by an influx of macrophages and neutrophils into the myometrium and cervix, with co-incident increased peripheral blood monocyte activation. Infection and inflammation are strongly implicated in the pathology of preterm labour (PTL), with progesterone considered a promising candidate for its prevention or treatment. In this study, we investigated the effect of monocytes on myometrial smooth muscle cell inflammatory cytokine production both alone and in response to LPS, a TLR4 agonist used to trigger PTL in vivo. We also investigated the effect of monocytes on myocyte contraction. Monocytes, isolated from peripheral blood samples from term pregnant women, were cultured alone, or co-cultured with PHM1-41 myometrial smooth muscle cells, for 24 h. In a third set of experiments, PHM1-41 myocytes were cultured for 24 h in isolation. Cytokine secretion was determined by ELISA or multiplex assays. Co-culture of monocytes and myocytes led to synergistic secretion of pro-inflammatory cytokines and chemokines including IL-6, IL-8 and MCP-1, with the secretion being further enhanced by LPS (100 ng/ml). The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell-cell contact, and by TNF. Conditioned media from co-cultures stimulated contraction of PHM1-41 myocytes, and the effect was inhibited by progesterone. Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion. These data suggest that monocytes infiltrating the myometrium at labour participate in crosstalk that potentiates pro-inflammatory cytokine secretion, an effect that is enhanced by LPS, and can augment myocyte contraction. These effects are all partially inhibited by progesterone.


Assuntos
Citocinas/metabolismo , Monócitos/metabolismo , Miócitos de Músculo Liso/metabolismo , Miométrio/citologia , Miométrio/metabolismo , Progesterona/farmacologia , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Gravidez
8.
Clin Oncol (R Coll Radiol) ; 36(4): 243-253, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38336503

RESUMO

AIMS: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent. MATERIALS AND METHODS: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used. RESULTS: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made. CONCLUSIONS: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.


Assuntos
Melanoma , Humanos , Melanoma/cirurgia , Ontário , Revisões Sistemáticas como Assunto
9.
Anal Bioanal Chem ; 405(21): 6891-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23881364

RESUMO

We report a simple, cost-effective, and label-free detection method, consisting of a platelet-derived growth factor (PDGF) binding aptamer and hydrophobic Ru(II) complex as a sensor system for PDGF. The binding of PDGF with the aptamer results in the weakening of the aptamer-Ru(II) complex, monitored by luminescence signal. A substantial enhancement in the luminescence intensity of Ru(II) complex is observed in the presence of aptamer due to the hydrophobic interaction. Upon addition of PDGF, the luminescence intensity is decreased, due to the stronger interaction between the aptamer and PDGF resulting in the displacement of Ru(II) complex to the aqueous solution. Our assay can detect a target specifically in a complex medium such as the mixture of proteins, at a concentration of 0.8 pM.


Assuntos
Aptâmeros de Nucleotídeos/química , Medições Luminescentes/métodos , Técnicas de Sonda Molecular , Fator de Crescimento Derivado de Plaquetas/análise , Mapeamento de Interação de Proteínas/métodos , Rutênio/análise , Rutênio/química , Sondas Moleculares/análise , Sondas Moleculares/química , Fator de Crescimento Derivado de Plaquetas/química , Coloração e Rotulagem
10.
Eur J Surg Oncol ; 49(10): 107004, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37573665

RESUMO

Disorders or differences of sexual development encompasses an important group of conditions that affects up to 1 in 5,000 live births. Many individuals living in the female gender includes Turner syndrome, congenital adrenal hyperplasia and conditions with 46XY karyotype such as gonadal dysgenesis (Swyer syndrome). Individuals are commenced on high dose oestrogen to initiate and maintain development of secondary sexual characteristics such as breasts which is paramount in them identifying in the female gender. We highlight the first case of a patient with Swyer syndrome who was treated with long term oestrogen therapy and later developed breast cancer. In individuals with gonadal dysgenesis, testicular malignancy is a recognised risk and is screened for. Prolonged exposure to exogenous and endogenous hormones can increase the risk of breast cancer however how much this risk increases in those taking high dose hormones is not documented in the literature. We aim to highlight the importance of breast cancer treatment and surgical reconstruction in this group and whether they should be considered for early breast cancer screening. CONCLUSION: It is imperative that triple assessment is undertaken in every patient with a breast lump, regardless of gender identification. Clinicians must not delay investigations in this patient group due to a misunderstanding of their condition. Those on long term hormone supplementation should be entered into the breast screening program at an earlier age with Magnetic Resonance Imaging surveillance. Careful consideration of post treatment endocrine therapy is required and under the care of the multi-disciplinary team.


Assuntos
Neoplasias da Mama , Disgenesia Gonadal 46 XY , Disgenesia Gonadal , Feminino , Humanos , Neoplasias da Mama/terapia , Estrogênios , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/cirurgia , Desenvolvimento Sexual
11.
Am J Transplant ; 12(5): 1240-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22300640

RESUMO

We sought to develop and validate a quantitative risk-prediction model for predicting the risk of posttransplant in-hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999-2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk-prediction model was developed using two-thirds of the cohort (random sample), internally validated in the remaining one-third, and independently validated in a cohort of 338 children transplanted during 2009-2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild-moderate vs. normal) and total bilirubin (≥ 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C-statistic (0.78) and the Hosmer-Lemeshow goodness-of-fit (p = 0.89) in the model-development cohort were replicated in the internal validation and independent validation cohorts (C-statistic 0.75, 0.81 and the Hosmer-Lemeshow goodness-of-fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in-hospital mortality. We conclude that this risk-prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in-hospital mortality in children and may be useful to guide decision-making around patient listing for transplant and timing of mechanical support.


Assuntos
Cardiopatias/cirurgia , Transplante de Coração/mortalidade , Mortalidade Hospitalar/tendências , Modelos Estatísticos , Medição de Risco/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Masculino , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia
12.
J Fluoresc ; 22(5): 1345-56, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22699809

RESUMO

The investigation of the interaction of ruthenium(II)-bipyridine-tert-butylcalix[4]arene complexes (Rubc2 and Rubc3) with proteins (BSA and ovalbumin) using absorption, emission, excited state lifetime and circular dichroism techniques and by docking studies show that luminophore-receptor system bind strongly with proteins. An enhancement of absorption as well as emission intensity of Ru(II)-calixarene complexes in the presence of proteins, but the quenching of the emission intensity of proteins in the presence of Ru(II)-calixarene complexes are the interesting observations. The enhancement of emission intensity of Ru(II)-calixarene complex, in the presence of proteins, is due to the fluorescence resonance energy transfer (FRET) from protein to Ru(II)-calixarene complex. Among the two Ru(II)-calixarene complexes synthesized Rubc3 has more efficient binding and energy transfer than Rubc2 and BSA, with a large cavity size, has the advantage for binding over ovalbumin. Docking studies reveal that the presence of tert-butylcalix[4]arene moiety in Ru(II)-calixarene complexes facilitates binding with proteins. After the binding of Rubc2 and Rubc3 with proteins, the nearby fluorophores present in proteins are in optimal distance from the ruthenium centre for efficient FRET process to occur.


Assuntos
2,2'-Dipiridil/química , Calixarenos/química , Transferência Ressonante de Energia de Fluorescência , Simulação de Acoplamento Molecular , Compostos Organometálicos/metabolismo , Ovalbumina/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Compostos Organometálicos/química , Ovalbumina/química , Ligação Proteica , Conformação Proteica , Rutênio/química , Soroalbumina Bovina/química
13.
Mol Cancer Ther ; 21(8): 1273-1284, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35579893

RESUMO

Glioblastoma stem cell (GSC) is the major cause of glioblastoma multiforme (GBM) chemotherapy failure. Hypoxia is one of the determinants of GSC. NF-κB plays a pivotal link between hypoxia and cancer stem cells (CSCs). Disulfiram, an antialcoholism drug, has very strong NF-κB-inhibiting and anti-CSC activity. In this study, the in vitro anti-GSC activity of disulfiram and in vivo anti-GBM efficacy of poly lactic-co-glycolic acid nanoparticle-encapsulated disulfiram (DS-PLGA) were examined. We attempt to elucidate the molecular network between hypoxia and GSCs and also examined the anti-GSC activity of disulfiram in vitro and in vivo. The influence of GSCs and hypoxia on GBM chemoresistance and invasiveness was studied in hypoxic and spheroid cultures. The molecular regulatory roles of NF-κB, hypoxia-inducible factor-1α (HIF1α), and HIF2α were investigated using stably transfected U373MG cell lines. The hypoxia in neurospheres determines the cancer stem cell characteristics of the sphere-cultured GBM cell lines (U87MG, U251MG, U373MG). NF-κB is located at a higher hierarchical position than HIF1α/HIF2α in hypoxic regulatory network and plays a key role in hypoxia-induced GSC characters. DS inhibits NF-κB activity and targets hypoxia-induced GSCs. It showed selective toxicity to GBM cells, eradicates GSCs, and blocks migration and invasion at very low concentrations. DS-PLGA efficaciously inhibits orthotopic and subcutaneous U87MG xenograft in mouse models with no toxicity to vital organs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Dissulfiram/metabolismo , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Hipóxia/metabolismo , Camundongos , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo
14.
J Fluoresc ; 21(4): 1729-37, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21360295

RESUMO

Electron-transfer(ET) from organic sulfides to excited state rhenium(I)-based heteroleptic tricarbonyl complexes [Re(bpy)(CO)(3)(py)](+) (I) and [Re(bpy)(CO)(3)(ind))](+) (II) in acetonitrile solution is facile and luminescence quenching constants, k(q), are in the range 10(5)-10(8) M(-1)s(-1). The detection of the sulfide radical cation in this system using time-resolved absorption spectroscopy is a direct evidence for the ET nature of the reaction. The k(q) values for the quenching of Re(I)-complexes with organic sulfides are analyzed with a scheme involving rate controlling electron transfer process. The measured rate constants for the electron transfer (ET) reaction are close to the values calculated from Marcus theory.


Assuntos
Luminescência , Compostos Organometálicos/química , Rênio/química , Sulfetos/química , Transporte de Elétrons , Medições Luminescentes , Estrutura Molecular , Compostos Organometálicos/síntese química , Estereoisomerismo
15.
Curr Oncol ; 27(1): e43-e52, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32218667

RESUMO

Background: Previous versions of the guideline from the Program in Evidence-Based Care (pebc) at Ontario Health (Cancer Care Ontario) recommended that the use of high-dose interferon alfa 2b therapy be discussed and offered to patients with resected cutaneous melanoma with a high risk of recurrence. Subsequently, several clinical trials in patients with resected or metastatic melanoma found that immune checkpoint inhibitors and targeted therapies have a benefit greater than that with interferon. It was therefore considered timely for an update to the guideline about adjuvant systemic therapy in melanoma. Methods: The present guideline was developed by the pebc and the Melanoma Disease Site Group (dsg). Based on a systematic review from a literature search conducted using medline, embase, and the Evidence Based Medicine Reviews databases for the period 1996 to 28 May 2019, the Working Group drafted recommendations. The systematic review and recommendations were then circulated to the Melanoma dsg and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations: For patients with completely resected cutaneous or mucosal melanoma with a high risk of recurrence, the recommended adjuvant therapies are nivolumab, pembrolizumab, or dabrafenib-trametinib for patients with BRAF V600E or V600K mutations; nivolumab or pembrolizumab are recommend for patients with BRAF wild-type disease. Use of ipilimumab is not recommended. Molecular testing should be conducted to help guide treatment decisions. Interferon alfa, chemotherapy regimens, vaccines, levamisole, bevacizumab, bacillus Calmette-Guérin, and isolated limb perfusion are not recommended for adjuvant treatment of cutaneous melanoma except as part of a clinical trial.


Assuntos
Quimioterapia Adjuvante/métodos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Feminino , Guias como Assunto , Humanos , Masculino , Recidiva Local de Neoplasia , Ontário , Fatores de Risco , Melanoma Maligno Cutâneo
16.
Neuroscience ; 159(2): 618-28, 2009 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-19167461

RESUMO

Ca(v)2.2 high voltage-gated calcium channels are regulated by phorbol-12-myristae, 13-acetate (PMA) via Ser/Thr protein kinase C (PKC) phosphorylation sites in the I-II linker and C-terminus of the alpha(1) 2.2 subunit. Here we show that PMA enhancement of Ca(v)2.2 currents expressed in Xenopus oocytes can be blocked by inhibitors of PKC betaII or PKC epsilon isozymes, as shown previously for Ca(v)2.3 currents, and that microinjection of PKC betaII or PKC epsilon isozymes in the oocytes expressing the WT Ca(v)2.2 channels increases the basal barium current (I(Ba)). The I-V plot shows a large increase in current amplitude with PKC betaII and PKC epsilon isozymes with only a small shift in the peak I(Ba) in the hyperpolarizing direction. The potentiation of Ca(v)2.2 currents by microinjection of PKC betaII and PKC epsilon isozymes was not altered by the inhibition of G proteins with GDPbetaS. The combination of isozyme specific inhibitors with previously generated Ser/Thr to Ala mutants of alpha(1) 2.2 subunit revealed that PKC betaII or PKC epsilon isozymes (but not PKC alpha or delta) can provide full enhancement through the stimulatory site (Thr-422) in the I-II linker but that PKC epsilon is better at decreasing channel activity through the inhibitory site Ser-425. The enhancing effect of PKC betaII or epsilon at Thr-422 is dominant over the inhibitory effect at Ser-425. Injected PKC betaII also enhances Ca(v)2.2 current when any of the potential stimulatory sites (Ser-1757, Ser-2108 and Ser-2132) are available in the C-terminus. PKC epsilon provides lesser enhancement with C-terminal sites and only with Ser-2108 and Ser-2132. Sites Ser-1757 and Ser-2132, but not Ser-2108, are dominant over the inhibitory site Ser-425. Collectively, these results reveal a hierarchy of regulatory sites in Ca(v)2.2 channels. Site-specific regulation by different PKC isozymes may allow graded levels of channel activation and susceptibility or resistance to subsequent stimulatory events.


Assuntos
Canais de Cálcio Tipo N/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteína Quinase C-épsilon/metabolismo , Proteína Quinase C/metabolismo , Proteínas de Xenopus/metabolismo , Animais , Ácido Aspártico/genética , Canais de Cálcio Tipo N/efeitos dos fármacos , Canais de Cálcio Tipo N/genética , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Guanosina Difosfato/análogos & derivados , Guanosina Difosfato/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Microinjeções/métodos , Mutação/genética , Oócitos , Técnicas de Patch-Clamp , Ésteres de Forbol/farmacologia , Fosforilação/genética , Proteína Quinase C/genética , Proteína Quinase C/farmacologia , Proteína Quinase C beta , Proteína Quinase C-épsilon/genética , Proteína Quinase C-épsilon/farmacologia , Estrutura Terciária de Proteína/fisiologia , RNA Interferente Pequeno/farmacologia , Serina/genética , Serina/metabolismo , Tionucleotídeos/farmacologia , Treonina/genética , Proteínas de Xenopus/efeitos dos fármacos , Proteínas de Xenopus/genética , Xenopus laevis
17.
Indian Heart J ; 71(3): 272-276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543201

RESUMO

BACKGROUND: Isolated diastolic hypertension (IDH) has been actively discussed for the last two decades because of its prevalence in a younger population and its association with cardiovascular disease. Furthermore, the association of IDH is significant in South Asian Countries such as India because relatively younger populations are known to have a higher risk of cardiovascular events. OBJECTIVE: The objective of this study is to find prevalence of IDH and its risk correlates in a semiurban population of South Indian state of Andhra Pradesh. METHODS: Data were collected using the modified World Health Organization - STEPwise approach to Surveillance (WHO STEPS) questionnaire for 16,636 individuals from a group of villages under Thavanampalle Mandal. Collated data were analyzed for prevalence and risk factors of IDH. RESULTS: Prevalence of IDH was found to be 4.0% with mean age of 46.0 (±SD 13.6) years and a relatively higher prevalence in men (5.3%) as compared with women (3.2%). The prevalence of IDH peaked in the fifth decade of life (40-49 years of age) and declined thereafter. Among various risk factors that were analyzed for their association with IDH, only age, body weight, and body mass index retained their significance in multivariate binary logistic regression analysis. CONCLUSION: There is a significant prevalence of IDH below 50 years of age in the semiurban population of South India. As IDH in young and middle age is known to be associated with increased risk of cardiovascular events and end organ involvement, it highlights need for study and development of effective IDH management strategies to reduce associated morbidity and mortality.


Assuntos
Hipertensão/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Diástole , Feminino , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Tamanho da Amostra , Fatores Socioeconômicos , Adulto Jovem
18.
Curr Clin Pharmacol ; 14(2): 141-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30417794

RESUMO

BACKGROUND: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. METHODS: The toxicity of aspirin and aspirin derivatives to OC and a CRC cell line were investigated in the presence and absence of platins. RESULTS: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 colorectal cancer (CRC) cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. CONCLUSION: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins.


Assuntos
Antineoplásicos/farmacologia , Aspirina/análogos & derivados , Aspirina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Aspirina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Sinergismo Farmacológico , Humanos , Compostos Organoplatínicos/farmacologia , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico
19.
Cochrane Database Syst Rev ; (1): CD001765, 2008 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-18253995

RESUMO

BACKGROUND: Obsessive compulsive disorder is a common and disabling disorder. A significant proportion of patients manifest a chronic course. Individual randomised controlled trials (RCTs) have shown that selective serotonin re-uptake inhibitors (SSRIs) are effective in this condition. Previous systematic reviews or meta-analyses summarising the evidence are methodologically problematic or limited in the scope of their analysis. OBJECTIVES: To examine the efficacy and adverse effects of serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD) in adults. SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched on 12/11/2007. Reference lists were checked. Experts in the field were contacted. SELECTION CRITERIA: All RCTs and quasi-RCTs examining the efficacy of SSRIs compared with placebo for OCD in adults were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Selection of studies and data extraction were carried out by two review authors independently, and quality assessment of studies was undertaken. Data analysis was conducted using Review Manager software. Summary measures were produced using the weighted mean difference (WMD) for continuous data and relative risk (RR) for dichotomous data, with 95% confidence intervals (CI). SSRIs were examined as an overall group of drugs, and as individual drugs. MAIN RESULTS: Seventeen studies were included in the review, involving 3097 participants. Based on all 17 studies, SSRIs as a group were more effective than placebo in reducing the symptoms of OCD between 6 and 13 weeks post-treatment, measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS) (WMD -3.21, 95% CI -3.84 to -2.57). The WMD for individual SSRI drugs were similar and not statistically different. Based on 13 studies (2697 participants), SSRIs were more effective than placebo in achieving clinical response at post-treatment (RR 1.84, 95% CI 1.56 to 2.17). The pooled RR was shown to be similar between individual SSRI drugs. Although reported adverse effects data were more limited, with few exceptions, the overall and individual adverse effects for the different SSRIs were always worse than for placebo and, in the majority of cases, the difference was statistically significant. Nausea, headache and insomnia were always reported amongst the most common adverse effects in trials of each of the drugs. AUTHORS' CONCLUSIONS: SSRIs are more effective than placebo for OCD, at least in the short-term, although there are differences between the adverse effects of individual SSRI drugs. The longer term efficacy and tolerability of different SSRI drugs for OCD has yet to be established.


Assuntos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Humanos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Mar Pollut Bull ; 57(1-5): 125-36, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18093619

RESUMO

Macrozoobenthic assemblages and stable carbon (delta(13)C) and nitrogen (delta(15)N) isotope values of various primary producers (macroalgae and angiosperms) and consumers (macroinvertebrate filter/suspension feeders, deposit feeders, detritivores/omnivores and carnivores and fishes) were studied in the Santa Giusta lagoon (Sardinia, Italy) before (spring) and after (autumn) a dystrophic event which occurred in the summer of 2004. A few days after the dystrophy, the physico-chemical characteristics of sediments and macrozoobenthic assemblages were also investigated. In the latter occasion, high total organic carbon (3.9%) and organic matter (15.9%) contents of surface sediments went together with peaks in acid-volatile sulphide concentrations. Certain immediate effects were quite extreme, such as the drastic reduction in macrozoobenthos and the massive fish kill in August 2004. Among the macrozoobenthos, there were few individuals of chironomid larvae and Capitella cf. capitata left. However, by October, chironomid larvae were numerous, indicating a lack of predators (e.g. fish) and competitors. In addition, some bivalve species and polychaetes which were absent, or present in small numbers before the event, became relatively numerous. The results are discussed based on a knowledge of the sulphide tolerance of these species. Stable isotope analysis clearly showed that the basal level of the food web for most consumers consisted mainly of macroalgae and sedimentary organic matter, and that the values before and after the dystrophic event were not significantly different from one another. This indicates that the relations among different trophic levels were quickly restored following the dystrophic event.


Assuntos
Anaerobiose/fisiologia , Biodiversidade , Cadeia Alimentar , Sedimentos Geológicos , Invertebrados/fisiologia , Sulfetos/metabolismo , Animais , Isótopos de Carbono/análise , Sedimentos Geológicos/química , Itália , Isótopos de Nitrogênio/análise , Oceanos e Mares , Oxigênio/análise , Densidade Demográfica , Água do Mar/química , Temperatura
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