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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. / Objective: This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. Study Design: We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. Results: Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD 20.03, 95%CI 20.32 to 0.27; p = 0.9). Similarly, non-fasting/ fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, 20.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMAIR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p, 0.00001). Conclusions: Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.

Thesis (M.S.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references (ℓ. 46-53)

Made available in DSpace on 2014-06-11T19:35:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-09-02Bitstream added on 2014-06-13T20:06:47Z : No. of bitstreams: 1 salerno_t_dr_botfmvz.pdf: 1479294 bytes, checksum: 37333e3500ad6a6f49d6aabf4f562cf3 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O presente estudo avaliou a qualidade microbiológica, as características físicoquímicas e a presença de resíduos de antimicrobianos em leite de mulheres, vacas e cabras, bem como investigou a multirresistência bacteriana à antimicrobianos e a detecção de genes e produção de toxinas em linhagens de Staphylococcus spp. Foram colhidas 240 amostras de leite de mulheres encaminhadas ao Banco de Leite Humano (BLH) de Botucatu, SP, 200 amostras de leite de vacas com mastite e 200 de vacas sem mastite. Iguais quantidades de amostras de leite foram colhidas de cabras com e sem mastite. Dentre os tetos amostrados de vacas e cabras com mastite, 85,50% e 97,50% respectivamente acusaram mastite subclínica no CMT. A mastite clínica foi observada em 14,50% dos tetos de vacas e 2,50% dos tetos de cabras amostrados. A presença de micro-organismos em leite de vacas e cabras sem mastite foi verificada em cerca de 25,00% das amostras de leite testadas, alertando para a presença de animais portadores de patógenos no rebanho. A acidez dornic do leite de mulheres revelou que 95,42% encontraram-se dentro dos limites aceitáveis pela Rede Nacional de BLH. O aporte calórico do leite humano (LH) apresentou ampla variação nos teores de creme, gordura e valor energético. A acidez dornic do leite de vacas e cabras com e sem mastite apresentaram ampla variação indicando que outros fatores, além da contaminação microbiana do leite, podem interferir nos índices de acidez titulável. Staphylococcus spp. e Enterobacter spp. foram os isolados mais frequentes em amostras de LH. Streptococcus spp., Staphylococcus spp. e Corynebacterium bovis foram os micro-organismos mais comumente... / The present study evaluated the microbiological quality, the characteristics physicist-chemistries and the presence of antimicrobials residues in milk of women, cows and goats, as well as investigated the bacterial multidrug resistance and the detection of genes and/or toxin production in Staphylococcus spp. strains. Was collected 240 milk samples from women referred to the Human Milk Bank (HMB) in Botucatu, 200 milk samples from cows with mastitis and 200 cows without mastitis. Equal amounts of milk samples were collected from goats with and without mastitis. Among the sampled cows and goats teats with mastitis, 85.50% and 97.50% respectively accused subclinical mastitis on CMT. Clinical mastitis was observed in 14.50% of cows teats and 2.50% of the sampled goats teats. The presence of microorganisms in milk from cows and goats without mastitis was found in about 25.00% of the milk samples tested, warning of the presence of pathogens from animals in the herd. Dornic acidity of woman’s milk revealed that 95.42% were within acceptable limits by the National Network of HMB. Calorie intake of human milk (HM) showed wide variation in the amounts of cream, fat and energy value. Dornic acidity of cows and goats milk with and without mastitis showed wide variation indicating that other factors in addition to microbial contamination of milk can interfere with acidity indices. Staphylococcus spp. and Enterobacter spp. were the most frequently isolated in samples of human milk. Streptococcus spp., Staphylococcus spp. and Corynebacterium bovis were the microorganisms most commonly isolated in milk cows with and without mastitis. In milk samples from goats with and without... (Complete abstract click electronic access below)

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Dimitrios Vagiannis Supervisor RNDr. Jakub Hofman, Ph.D. Title of Doctoral Thesis Study on the role of pharmacokinetic mechanisms of drug resistance in new anticancer drugs with focus on solid tumors Cancer chemotherapy is an important tool for the cure of cancer. Although the development of new anticancer drugs has been rapidly progressing, the phenomenon of multidrug resistance (MDR) continues to be a key issue leading to therapy failure in oncological patients. MDR is based on pharmacodynamic as well as pharmacokinetic mechanisms. Pharmacokinetic MDR includes drug efflux transporters and biotransformation enzymes that decrease the amount of (active form of) a drug in tumors. While the MDR role of transporters has been well understood, the participation of drug metabolizing enzymes is still unclear. This thesis investigates the role of cytochromes P450 (CYPs) in cytostatic resistance. Furthermore, it focuses on the modulation of pharmacokinetic MDR using pharmacokinetic drug-drug interactions of new targeted antitumor drugs. Finally, it aims to confirm the in vitro findings in ex vivo patient-derived tumor explants. In our latest publication, we demonstrate the significant role of...

A resistência à insulina é um problema cada vez mais presente na rotina clínica dos veterinários que trabalham com equídeos. A hiperinsulinemia resultante da resistência à insulina está associada a diversas alterações fisiológicas e podem levar a enfermidades graves como a Síndrome Metabólica Equina ou a Laminite que podem culminar na invalidez ou até morte do animal. O diagnóstico da resistência à insulina em equinos é baseado em modelos dos mesmos testes realizados em humanos. Até a presente data não há testes práticos, acessíveis e com sensibilidade e especificidade suficientemente capazes de diagnosticar a resistência à insulina em equinos. Em humanos e outros modelos animais a frutosamina é um biomarcados utilizado no diagnostico da resistência a insulina. A dosagem de frutosamina sérica é simples e barata, porém, seu uso no diagnostico da resistência à insulina em equinos ainda não foi testado. O presente estudo tem como objetivo avaliar a frutosamina em cavalos estabulados e sedentários diagnosticados com resistência à insulina por três diferentes métodos descritos em literatura sendo estes: Teste Combinado de Glicose e Insulina, Reciproco da Raiz Quadrada da Insulina (RRQI) e Relação Glicose-Insulina Modificada (RGIM). Além disso avaliamos a incidência de resistência à insulina em cavalos estabulados e sedentários. Todos os testes foram capazes de identificar grupos resistentes e não resistentes a insulina, porém com baixo concordância entre si. Apesar disso a dosagem de frutosamina sérica não diferiu entre os grupos formados a partir de qualquer um dos métodos diagnósticos de resistência à insulina. / Insulin resistance is an increasing problem in the clinical routine of equine veterinarians. The hyperinsulinemia resulting from insulin resistance is associated with several physiologic alterations and can lead to serious diseases like equine metabolic syndrome or laminitis which can to early retirement or animal death. Equine insulin resistance diagnosis is based in human tests. Until now, there is no practical, accessible, sensible and specificity test capable of diagnosing equine insulin resistance. In human and other animals model, frutosamine is simple and cheap biomarker use in this diagnosis, however its use for equine insulin resistence diagnosis never had been tested. The aim of the present study was to evaluate the fructosamine in stable and sedentary horses diagnosed with or without insulin resistance by three different methods described in the literature (Combined Glucose and Insulin Test - TCGI, Reciprocal of the Square Root of Insulin (RISQI) and Modified Insulin-to-Glucose Ratio (MIRG). For this, 17 adult male horses were evaluated. All tests were able to identify resistant and not resistant to insulin animals, but with low concordance between them. Regardless of the test used, the serum fructosamine dosage did not differ between the resistant and non-insulin resistant groups and could not be used as an early marker for insulin resistance in horses.

O fluoreto (F) é amplamente empregado na Odontologia para o controle da cárie dentária. Entretanto apesar de suas propriedades terapêuticas, também pode oferecer riscos ao organismo se aplicado ou consumido de maneira indiscriminada ou inadequada. São encontrados estudos em humanos associando o consumo excessivo de F com intolerância à glicose. Estudos com animais submetidos a doses agudas ou crônicas altas de F revelam alterações na cascata de sinalização insulínica. Entretanto, seu efeito quando administrado em doses crônicas associadas àquelas equivalentes em humanos que recebam níveis ótimos de F através da água artificialmente fluoretada ou níveis aumentados através da água naturalmente fluoretada, ou ainda quando administrado a animais com diabetes já instalada, nunca foi testado. O presente trabalho teve por objetivo avaliar, em ratos normais ou com diabetes já instalada, expostos cronicamente a doses de F na água de beber que simulam a ingestão de F pela água natural e artificialmente fluoretada, parâmetros relacionados à interferência do F na resistência à insulina. Para tanto, foram utilizados inicialmente 214 ratos Wistar, com 60 dias de idade. Dentre estes, foi induzido diabetes em 133 animais por injeção intraperitoneal de estreptozotocina (50 mg/Kg peso corporal), sendo que 111 animais tiveram diabetes confirmado e foram aleatoriamente alocados a 3 grupos, diferindo em relação à concentração de F na água de beber (0, 10 ou 50 ppm), com a qual foram tratados por 22 dias. Oitenta e um animais não diabéticos foram também aleatoriamente alocados a estes 3 grupos. Decorrido o período experimental, os animais foram eutanasiados e foram avaliados: fluoremia, glicemia, insulinemia, concentração de F no fígado, a velocidade de desaparecimento da glicose sanguínea após estímulo insulínico (KITT), a resistência à insulina (HOMA2-IR), sensibilidade à insulina (%S) e função das células β pancreáticas (%B) e grau de fosforilação em tirosina do substrato do receptor de insulina pp185 (IRS-1/IRS-2) após estímulo insulínico, em tecidos muscular e hepático (Western blotting). As análises laboratoriais revelaram que: 1) houve dose-resposta para as concentrações de F no plasma e no fígado, sendo as concentrações maiores nos animais diabéticos comparados aos não diabéticos; 2) a glicemia não foi alterada mediante exposição ao F, tanto para animais não diabéticos quanto para animais diabéticos, embora estes tenham apresentado glicemias significativamente mais altas que aqueles; 3) os animais diabéticos apresentaram uma insulinemia significativamente menor quando comparados aos não diabéticos e o tratamento com F não afetou a insulinemia nos animais não diabéticos, mas a reduziu nos diabéticos, sem efeito dose-resposta; 4) a KITT foi significativamente menor nos animais diabéticos comparados aos não diabéticos (controle e tratados com 10 ppm F); 5) independentemente do tratamento com F, a %B nos animais diabéticos foi significativamente menor que aquela observada para os não diabéticos; 6) o índice HOMA2-IR e a %S não apresentaram diferenças significativas nem para os tratamentos com F nem para os animais diabéticos e não diabéticos, sendo que para aqueles foi observada uma tendência de aumento nos grupos tratados com F, especialmente para o grupo de 10 ppm F; 7) não houve alteração significativa no grau de fosforilação em tirosina da pp185 em função do tratamento com F. / Fluoride (F) is broadly used in Dentistry for caries control. However, despite its therapeutic properties, when used in excess, toxic signs and symptoms may occur. Studies conducted with humans have reported association between excessive F intake and glucose intolerance. Studies conducted with animals submitted to acute or high chronic doses of F have revealed alterations in the insulin signaling pathway. However, its effect when administered in chronic doses that simulate those present in the artificially or naturally fluoridated water ingested by humans, or when ingested by diabtetic animals, was not evaluated before. The present study aimed to evaluate in normoglycemic or diabetic rats chronically exposed to water containing F levels that simulate those present in the artificially or naturally fluoridated water, parameters related to the interference of F in the insulin resistance. For this purpose, 214 60-dayold Wistar rats were initially employed. Among these, diabetes was induced in 133 animals through intraperitoneal injection of streptozotocin (50 mg/Kg body weight).From these, 111 diabetic animals were randomly allocated to 3 groups that differed according to the F concentration on the water (0, 10 or 50 ppm) that was drank for 22 days. Eight-one non-diabetc animals were allocated to the same groups. After the experimental period, animals were euthanized and the following parameters were evaluated: fluoremia, glucemia, insulinemia, F concentration in the liver, velocity of disappearance of blood glucose (KITT), insulin resistance (HOMA2-IR), insulin sensitivity (%S), function of β pancreatic cells (%B), degree of insulin receptor substrate tyrosine phosphorylation state (pp 185, IRS-1/IRS-2) - after insulin stimulus in liver and muscle (Western blotting). Laboratory analyses revealed: 1) doseresponse for plasma and liver F concentrations that were higher in the diabetic animals compared to those non-diabetic; 2) glucemia was not altered upon exposure to F, both for non-diabetic and diabetic animals, despite the latter presented higher values compared to the first; 3) diabetic animals had significantly lower insulinemia when compared to non-diabetic animals; treatment with F did not affect insulinemia in non-diabetic animals, mas reduced this parameter in diabetic animals, without dose-response; 4) KITT was significantly lower in diabetic animals compared to non-diabetic animals (control and treated with water containing 10 ppm F); 5) Regardless treatment with F, %B in diabetic animals was significantly lower than the same parameter in non-diabetic animals; 6) HOMA2-IR and %S did not present significant differences in function of treatment with F or condition (diabetes or not); for the diabetic animals these parameters were slightly increased in the groups treated with F (specially 10 ppm F); 7) the status of phosphorylation of pp185 did not change upon treatment with F.

In unsteady flows, dune dimensions may vary considerably from fully-developed dimensions produced from a flat bed under a steady and uniform flow. Specifically, dune height and length are observed to lag discharge when the flow is non-steady, resulting in dimensions that are out of phase with the prevailing flow. This research attempts to provide some insight into the behaviour of dunes when the flow is suddenly changed, as well as the time-scale of the related dune changes. Nineteen experimental runs were carried out in the 21-m long, 0.76-m wide Sediment Transport Flume at Queen’s University. In ten of these runs the flow depth, h, was suddenly increased (h2/h1 > 1) and in nine runs the flow depth was suddenly decreased (h2/h1 < 1). In all runs, the slope of free surface was kept equal to the slope of the bed such that the change in flow rate is represented by the change in the flow depth. Seven ratios of the two flow depths, h2/h1 (varying between 0.49 and 2.29), were performed for three slopes (S = 1/792, 1/534, 1/341). The bed material was a coarse, poorly-graded silica sand (D50 = 1.0 mm). Longitudinal bed profiles were taken along the centreline of the flume approximately every 6–8 minutes to determine the transient dune dimensions and the time at which the dunes acquired their new equilibrium dimensions. This time is termed the duration of dune development, Td. Through dimensional and physical considerations, Bielenberg (2006) established that the dimensionless counterpart of Td should be a function of the material number, relative flow depth, relative flow intensity, and ratio of the flow depths h2/h1. The present experiments were carried out to investigate the influence of the relative flow intensity and h2/h1 on the duration of dune development. Results indicate that equilibrium dune dimensions do not depend on the initial shape of the bed. After the period Td, the dunes tend to be similar to those produced from a flat bed. It is found that Td is strongly dependent on h2/h1, and weakly dependent on the flow intensity. All other determining variables remaining the same, Td decreases with increasing values of flow intensity. Semi-empirical relations for the dimensionless duration of dune development are presented. / Thesis (Master, Civil Engineering) -- Queen's University, 2007-09-24 09:45:13.624

Thesis (Ph.D.)--University of Wollongong, 2005. / Typescript. Includes bibliographical references: p. 235-254.

Submitted by VITOR MULLER ANUNCIATO (vitor.muller@gmail.com) on 2018-04-20T22:14:14Z No. of bitstreams: 1 DissertaçãoANUNCIATOparaImpressão.pdf: 3297037 bytes, checksum: 5946e7250c31b4a24ba3c90890cb6318 (MD5) / Approved for entry into archive by Maria Lucia Martins Frederico null (mlucia@fca.unesp.br) on 2018-04-23T11:13:16Z (GMT) No. of bitstreams: 1 anunciato_vm_me_botfca.pdf: 3297037 bytes, checksum: 5946e7250c31b4a24ba3c90890cb6318 (MD5) / Made available in DSpace on 2018-04-23T11:13:16Z (GMT). No. of bitstreams: 1 anunciato_vm_me_botfca.pdf: 3297037 bytes, checksum: 5946e7250c31b4a24ba3c90890cb6318 (MD5) Previous issue date: 2018-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Muito já foi e ainda vem sendo estudado sobre os efeitos clássicos de dose-resposta dos herbicidas e uma outra vertente que vem surgindo são as respostas bifásicas, que incluem hormesis, caracterizada por doses baixas de um herbicida que causa estímulo e inibição em dose elevada. Assim como o estímulo pode ser benéfico na agricultura em algumas aplicações, porem quando ocorre em plantas não alvo, o efeito de hormesis pode-se tornar um problema. Nesse trabalho foram realizados quatro experimentos. Um experimento de curva dose-resposta para biótipo resistente e suscetível de Digitaria insularis, resistente ao herbicida glyphosate, avaliando-se altura das plantas, massa fresca e seca e fitotoxicidade (%) aos 7, 14 e 21 dias após a aplicação. Houve também a repetição do mesmo, um experimento com subdosagem de glyphosate para averiguar o efeito das subdosagens no florescimento, avaliando-se o número de panículas emitidos após a aplicação dos tratamentos e o quarto experimento que foi a verificação da germinação, índice de velocidade de germinação e peso de sementes provindas do terceiro experimento. O efeito de estímulo das subdoses foram constatados em todos os experimentos sendo que diferentes faixas de doses causaram o efeito de hormesis nos biótipos de D.insularis, resistente e suscetível havendo aumento de altura, massa, peso de sementes e velocidade de germinação e diminuição do tempo necessário para emissão das inflorescências. Esses efeitos podem conceder uma grande vantagem para a disseminação dessa espécie, auxiliando a alteração da flora de plantas infestantes. / Currently much has been studied about the classic dose-response effects of herbicides and another aspect that is emerging are the biphasic responses, which include hormesis, a biphasic dose-response phenomenon characterized by low dose stimulation and high dose inhibition. Just as the stimulus may be beneficial in agriculture in several applications, when this stimulus occurs in non-target plants, the effect of hormesis can become a problem. In this work, a dose-response curve experiment was performed for resistant and susceptible biotypes of Digitaria insularis, resistant to the glyphosate herbicide and evaluating plant height, fresh and dry mass and phytotoxicity (%) at 7, 14 and 21 days after application. The second experiment was the repetition of the firs. An experiment with subdoses of glyphosate are performed to investigate the effect of the subdoses on flowering, evaluating the number of panicles emitted after the application of the treatments and the fourth experiment that was the verification of the germination, germination speed index and seed weight from the third experiment. The effect of subdoses stimulation was observed in all the experiments, with different dose ranges causing the stimulus in the D.insularis biotypes, resistant and susceptible, increasing height, mass, seed weight and germination speed and reduced the time required for inflorescence emission. These effects can give a great advantage to the spread of this species, helping to change the flora of weeds.