13 research outputs found
Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma
No full textPurpose: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. Patients and Methods: The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101-1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. Results: Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. Conclusion: In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity. (C) 2003 by American Society of Clinical Oncology
A Inibição da síntese proteica no hipocampo dorsal de ratos impede a tolerância ao midazolam induzida pela experiência prévia no labirinto em cruz elevado
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2011A tolerância ao efeito do tipo ansiolítico de drogas pode se desenvolver como resultado de uma memória proveniente da experiência prévia em testes comportamentais, como o labirinto em cruz elevado (LCE). O envolvimento da amígdala basolateral na consolidação dessa informação já foi demonstrada. O hipocampo dorsal (HD) é uma região encefálica responsável pela consolidação das memórias de longa duração, um processo que depende da síntese de novas proteínas. No entanto, não se sabe se o bloqueio da síntese proteica no HD preveniria a tolerância ao efeito do tipo ansiolítico de uma droga no reteste no LCE em animais nunca expostos a essa droga. Para investigar isso, foram realizadas infusões bilaterais de anisomicina (ANI; 80 µg/hemisfério), um inibidor da síntese proteica, no HD de ratos 0, 3 ou 6 h após, ou 15 min antes do teste no LCE. A infusão de ANI no HD próxima à sessão de teste no LCE manteve o efeito do tipo ansiolítico do midazolam (MDZ; 0,5 mg/kg i.p.) em ratos retestados no LCE 24 h depois, sugerindo que a informação consolidada por meio da síntese proteica no HD passa a influenciar a resposta comportamental do animal frente a esse benzodiazepínico. Para verificar se prejuízos na aquisição também poderiam explicar a prevenção da tolerância aos efeitos do MDZ provocada pela infusão de ANI antes do teste no LCE, a sessão de reteste foi realizada 3 h após, coincidindo com a janela temporal em que a memória de curta duração persiste, já que sua formação não requer a síntese proteica. Nesse caso, a infusão pré-teste de ANI no HD não impediu mais a tolerância ao MDZ no reteste. Esse resultado sugere que a inibição da síntese proteica promovida pela ANI no HD prejudicou seletivamente a consolidação, mas não a aquisição, da memória relacionada à experiência prévia no LCE. Também foi demonstrada a esquiva aumentada aos braços abertos na sessão de reteste no LCE em todos os experimentos. No entanto, a infusão de ANI no HD, nesse caso, não interferiu nesse padrão observado na exposição subsequente no teste comportamental. Pode-se confirmar, portanto, a participação da memória na tolerância induzida pela experiência prévia no LCE.Tolerance to the anxiolytic-like effect of drugs may be associated with the retrieval of an aversive memory acquired during a prior experience in certain apparatuses such as the elevated plus-maze (EPM). Activity in basolateral amygdala has been shown to be required for consolidating this information. In addition, the dorsal hippocampus (DH) has also been implicated in long-term memory consolidation, a process relying on new protein synthesis. It is unknown, however, whether the DH protein synthesis disruption would prevent the phenomenon rendering animals unresponsive to benzodiazepines in the EPM retest. To address this, the protein synthesis inhibitor anisomycin (ANI) was bilaterally infused into the rat DH 0, 3 or 6 h after, or 15 min before, the EPM test. DH infusion of ANI (80 µg) around the time of EPM testing preserved the anxiolysis of midazolam (MDZ; 0.5 mg/kg i.p.) in rats retested in the EPM 24 h later, suggesting that information consolidated by DH protein synthesis impacts on the subsequent animal.s responsiveness to this drug. To examine whether impaired memory acquisition could also contribute to the prevention of MDZ tolerance seen in EPM-experienced animals infused with ANI before testing, the EPM retest was performed 3 h after testing to coincide with the temporal window in which short-term memory remains, for the reason that this process does not require protein synthesis for its formation. The pretest DH anisomycin infusion.s ability to prevent the MDZ tolerance on retesting was now missing. This result has confirmed a specific action of the ANI on memory consolidation. We also found that rats express further avoidance to open-arms in the EPM retest. However, neither pretest nor posttest DH ANI infusion interfered with this pattern of results observed in EPM-experienced rats. In conclusion, the impact of memory formation, consolidated by DH protein synthesis, on the subsequent animal.s responsiveness to MDZ on EPM retest session could be confirmed
An evaluation of gastrocnemius muscle structure and function in endurance runners and low physical activity individuals
No full textIncludes abstract.Includes bibliographical references.Distance running has become increasingly popular in recreational runners. The gastrocnemius is the main muscle used for propulsion in running, and may be at risk for injury due to its morphology. In previous studies, changes in the morphology and architecture of the gastrocnemius muscle have been evident following training, but it is unclear whether these changes are related to training or youth. Previous studies of runners have shown a decrease in gastrocnemius and soleus flexibility, as well as changes in the fascicle length and pennation angle. Gastrocnemius volume has not been compared in low physical activity and active participants. Physiological cross sectional area, based on volume and fascicle length measurements may also provide valuable information about the muscle’s ability to produce force. Ultrasound may be a useful tool in assessing potential training adaptations in the morphology and architecture of the gastrocnemius muscle. The aim of this cross-sectional descriptive study was to assess the differences in architecture and function of the gastrocnemius in endurance runners compared to low physical activity participants. (a) To assess differences in calf function and flexibility between endurance runners and low physical activity individuals, and between male and female participants; (b) To determine differences in gastrocnemius muscle architecture and composition between endurance runners versus low physical activity individuals, and between males and females; and (c) To determine whether there are any relationships between training factors and the structure and function of the gastrocnemius muscle. Thirty participants between 20 and 45 years old were recruited for this study and allocated to groups based on their level of physical activity. The low physical activity group (n = 14) were not participating in any regular physical activity, while the endurance running group (n = 16) were running a minimum of 40 km.wk-1, and had participated in at least one full marathon (42.2 km) in the previous six months. All participants completed informed consent, a physical activity and training questionnaire, and a Physical Activity Readiness Questionnaire (PAR-Q) at the first session. The first session also included body composition measurements; ultrasound imaging to measure gastrocnemius length, thickness, fascicle length, pennation angle and volume; and familiarisation with all physical tests. Physical tests were conducted in the second session, including gastrocnemius and soleus flexibility, calf raise endurance and vertical jump height to assess the function of the components of the triceps surae. There were no significant differences between low physical activity and running groups for gastrocnemius thickness, fascicle length, pennation angle and gastrocnemius length. Gastrocnemius volume (p = 0.02) and physiological cross sectional area (p = 0.01) were significantly greater in the running group compared to the low physical activity group. There were no significant differences between low physical activity and running groups in flexibility or vertical jump height, although male participants had significantly decreased gastrocnemius muscle flexibility (p = 0.046) and significantly greater vertical jump heights (p = 0.01) than females. Calf raise endurance was significantly greater in the running group than in the low physical activity group (p = 0.03). Endurance running leads to specific adaptations in participants in both structure and function. While ultrasound appears to be a reliable measure for assessing architectural components of the gastrocnemius muscle in both active and inactive populations, further cadaver studies may provide valuable information on muscle architecture
Atividade física, sobrepeso e obesidade nos motoristas do transporte público em Manizales, Colômbia
No full textObjective: To determine the level of physical activity, overweight and obesity of public service drivers in the city of Manizales, Colombia. Methodology: quantitative, correlational and cross-sectional research. Simple random probability sampling. A sample of 175 male subjects was obtained from three public taxi service companies. The analysis was carried out with the SPSS v.20 program for Windows. Descriptive statistics were calculated. To determine the relationship between nonparametric variables, the MannWhitney U tests, Chi-square and the Pearson correlation index were applied. For the comparison of means in the parametric variables the t-Student test was used with a level of significance of p≤ 0.05. Results: average age, 48.89 ± 16.64 years; average height, 1.68 ± 0.05 m, average abdominal circumference, 94.92 ± 9.0 cm and average body mass index, 27.51 ± 3.4 kg/m2 . Intense physical activity was carried out by 19.3%, moderate intensity physical activity was practiced by 27.8%, and low intensity physical activity was carried out by 36.4%, while 16.5% of drivers do not perform any physical activity. Conclusions: Taxi drivers have low levels of intense and moderate physical activitywhile low levels of physical activity have a higher prevalence. Drivers are characterized because they are 63% overweight and have a high abdominal circumference index with values similar to the national parameters.Objetivo: determinar el nivel de actividad física, sobrepeso y obesidad en los conductores de servicio público de la ciudad de Manizales, Colombia. Metodología: investigación de tipo cuantitativo, correlacional y de carácter transversal. Muestreo probabilístico aleatorio simple; se obtuvo una muestra de 175 sujetos del género masculino, de tres empresas de servicio público de taxis. El análisis se realizó con el programa SPSS v.20 para Windows. Se calcularon los estadísticos de tipo descriptivo; para determinar la relación entre variables no paramétricas se aplicaron las pruebas U de Mann-Whitney, Chi-cuadrado y el índice de correlación de Pearson. Para la comparación de medias en las variables paramétricas se usó la prueba t-Student, con un nivel de significancia de p≤ 0,05. Resultados: edad promedio de 48,89±16,64 años; talla de 1,68±0,05 m, circunferencia abdominal de 94,92±9,0 cm y un índice de masa corporal de 27,51±3,4 kg/m2 ; la actividad física intensa es realizada por el 19,3%; la actividad física de intensidad moderada fue practicada por el 27,8%, y la actividad física de baja intensidad fue realizada por el 36,4%. El 16,5% no realiza actividad física. Conclusiones: Los conductores de taxi tienen bajos niveles de actividad física intensa y moderada, mientras que los niveles de actividad física baja tienen una prevalencia más alta. Se caracterizan por presentar sobrepeso del 63% y un elevado índice de circunferencia abdominal, con valores similares a los parámetros nacionales.Objetivo: determinar o nível de atividade física, sobrepeso e obesidade nos motoristas de transporte público da cidade de Manizales, Colômbia. Metodologia: pesquisa de tipo quantitativo, correlacional e de caráter transversal. Amostragem probabilística aleatória simples; foi obtida uma amostra de 175 sujeitos do gênero masculino, de três empresas de transporte público de taxis. A análise se realizou como programa SPSS v.20 para Windows. Foram calculados os estatísticos de tipo descritivo; para determinar a relação entre variáveis não paramétricas foram aplicados os testes U de Mann-Whitney, Chi-quadrado e o índice de correlação de Pearson. Para a comparação de médias nas variáveis paramétricas foi usado o teste t-Student, com um nível de significância de p≤ 0,05. Resultados: idade média de 48,89±16,64 anos; tamanho de 1,68±0,05 m, circunferência abdominal de 94,92±9,0 cm e um índice de massa corporal de 27,51±3,4 kg/m2 ; a atividade física intensa é realizada por 19,3%; a atividade física de intensidade moderada é praticada por 27,8%, e a atividade física de baixa intensidade é realizada é 36,4%. O 16,5% não realiza atividade física. Conclusões: Os motoristas de taxi têm baixos níveis de atividade física intensa e moderada, enquanto que os níveis de atividade física baixa têm uma prevalência mais alta. Um 63% dos motoristas apresentou um elevado índice de circunferência abdominal, com valores similares aos parâmetros nacionais
Mechanisms of multidrug resistance in bladder cancer: the role of the nuclear membrane
No full textMultidrug resistance (MDR) describes the phenomenon whereby cancer cellsexposed to a single cytotoxic drug develop cross resistance to numerous otherstructurally unrelated chemotherapeutics. The development of MDR is a majorcause of cancer chemotherapy treatment failure in all types of cancer.Numerous mechanisms of MDR have been elucidated which include ATPbindingcassette (ABC) transporter proteins, cytoplasmic vaults, alterations intopoisomerase II and increased expression of glutathione-S-transferases, all ofwhich result in reduced chemotherapeutic efficacy.Superficial bladder cancer is commonly treated with adjuvant intravesicalchemotherapy using mitomycin C or epirubicin (an anthracycline), followingsurgical resection. However, despite this treatment, the recurrence rates ofthese tumours can approach 60%. This high recurrence rate represents thedevelopment of MDR in many cases.Previous work using anthracycline fluorescence has shown that MDR cellshave reduced levels of anthracycline uptake and also demonstrate acharacteristic nuclear sparing of drug uptake. This nuclear sparingphenomenon in MDR cells transcends tissue type and suggests that thenuclear membrane may also play a role in MDR.The work described herein discusses the current role of chemotherapy in thetreatment of superficial bladder cancer, mechanisms of MDR and the role of thenuclear membrane in MDR. Following this our investigation of the role of thenuclear membrane is described, using a number of novel techniques includingcell fusion and microinjection. In addition, we investigated MDR modulation byverapamil, with analysis of changes in cellular, cytoplasmic and nuclear druguptake mediated by this known MDR reversing agent
Venetian cardinals at the Papal Court during the pontificates of Sixtus IV and Innocent VIII : 1471-1492
No full textThe histories of particular cities and states within that myriad-faceted
slice of civilisation, the Renaissance in Italy, have received
more scholarly attention than have the diplomatic, ecclesiastical and
cultural connections between them. This study is part of a balance-redressing
process. Senior clerics traversed frontiers, owing
allegiance to their native state, their benefices and, above all, to
the Papacy. The purpose of this exploration of the curial careers of
four later quattrocento Venetian cardinals is essentially twofold : to
account for relations between Venice and the Papacy with reference to
individuals who were at once Venetian patricians and princes of the
Church; and to examine the cardinals' responses to this situation in
terms of political, ecclesiastical and cultural patronage. Where did
their loyalty lie? To Venice, with its perennial suspicion of the
Church and peculiar notion of the characteristics of a Venetian
cardinal? Or to the Pope, expressing overt hostility towards the
Republic in the War of Ferrara and placing it under an interdict?
Chapter one sets Merco Barbo, Pietro Foscari, Giovanni Michiel and
Giovanni Battista Zeno in a Venetian context. Chapters two and three
chart relations between the two powers, from the exposure of Cardinal
Zeno's involvement in a scheme to transmit Venetian state secrets to
Rome in exchange for ecclesiastical preferment, through to Ermolao
Barbaro's controversial appointment to the patriarchate of Aquileia,
via the short-lived Papal-Venetian league negotiated by Cardinal
Foscari in 1480. The fourth chapter considers their proximity to the
Supreme Pontiff and how their material fortunes varied under popes
Sixtus and Innocent, after which an assessment of the nature, extent
and effectiveness of their patronage is divided between chapters five
and six, focussing pa.rticularly on Venetian connections. Despite
diverging careers, it is concluded that all were bound by variations
of the Venetian inheritance
Search for Lensing Signatures in the Gravitational-Wave Observations from the First Half of LIGO–Virgo’s Third Observing Run
No full textInternational audienceWe search for signatures of gravitational lensing in the gravitational-wave signals from compact binary coalescences detected by Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) and Advanced Virgo during O3a, the first half of their third observing run. We study: (1) the expected rate of lensing at current detector sensitivity and the implications of a non-observation of strong lensing or a stochastic gravitational-wave background on the merger-rate density at high redshift; (2) how the interpretation of individual high-mass events would change if they were found to be lensed; (3) the possibility of multiple images due to strong lensing by galaxies or galaxy clusters; and (4) possible wave-optics effects due to point-mass microlenses. Several pairs of signals in the multiple-image analysis show similar parameters and, in this sense, are nominally consistent with the strong lensing hypothesis. However, taking into account population priors, selection effects, and the prior odds against lensing, these events do not provide sufficient evidence for lensing. Overall, we find no compelling evidence for lensing in the observed gravitational-wave signals from any of these analyses
The sestiere of San Polo : a cross section of Venetian society in the second half of the fifteenth century
No full textThis thesis seeks to add to our understanding of Venetian
society in the latter half of the fifteenth century by
offering a new approach: an in-depth study of one of
Venice's six districts (sestier1). My researches
concentrated on the sestiere of San Polo, which embraced
the Rialto. My intention in narrowing the focus of analysis
is to reveal a cross-section of society. Fundamental to this
inquiry is to discover the identity of this sestiere; to
explore its little known social profile, trades and
solidarities and to sharpen the images of its urban fabric.
At the same time, it is an investigation into the
significance and role of neighbourhood and local loyalties
in Renaissance Venice. The opening chapter discusses the
changing topography of San Polo and its definition over the
following three centuries. Boundaries were blurred; parish
disputes document how and why they were changed. Chapter Two
introduces the three social orders recognised by
contemporaries (patriciate, citizenry and artisans), tracing
the sharpening of hierarchy, the growing cohesion of the
cittadini originarii and the emergence of poorer
neighbourhoods towards the city's margins. Chapter Three
investigates noble and cittadini families in San Polo,
through a number of detailed case studies. A complex and
varied picture emerged, in which family structures and
residential patterns amongst the nobility did not conform to
rigid models. Chapter Four attempts to flesh out a
collective portrait of the "little people", beginning with
Rialto. Chapters Five and Six discuss property; initially
through a massive survey after the Rialto fire (1514);
Quattrocento sources are then used to examine property at
Rialto, domestic housing, building activity and renting. The
final chapter deals with neighbourhood, concluding that the
sestiere was not an effective social unit and that local
loyalties formed part of complex and changing webs of
allegiance
Model comparison from LIGO–Virgo data on GW170817’s binary components and consequences for the merger remnant
No full textGW170817 is the very first observation of gravitational waves originating from the coalescence of two compact objects in the mass range of neutron stars, accompanied by electromagnetic counterparts, and offers an opportunity to directly probe the internal structure of neutron stars. We perform Bayesian model selection on a wide range of theoretical predictions for the neutron star equation of state. For the binary neutron star hypothesis, we find that we cannot rule out the majority of theoretical models considered. In addition, the gravitational-wave data alone does not rule out the possibility that one or both objects were low-mass black holes. We discuss the possible outcomes in the case of a binary neutron star merger, finding that all scenarios from prompt collapse to long-lived or even stable remnants are possible. For long-lived remnants, we place an upper limit of 1.9 kHz on the rotation rate. If a black hole was formed any time after merger and the coalescing stars were slowly rotating, then the maximum baryonic mass of non-rotating neutron stars is at most 3.05 M-circle dot, and three equations of state considered here can be ruled out. We obtain a tighter limit of 2.67 M-circle dot for the case that the merger results in a hypermassive neutron star
