Development of polymeric materials to inhibit bacterial quorum sensing

Bacterial infections are an increasing problem for human health. In fact, an increasing number of infections are caused by bacteria that are resistant to most antibiotics and their combinations. Therefore, the scientific community is currently searching for new solutions to fight bacteria and infectious diseases, without promoting antimicrobial resistance. One of the most promising strategies is the disruption or attenuation of bacterial Quorum Sensing (QS), a refined system that bacteria use to communicate. In a QS event, bacteria produce and release specific small chemicals, signal molecules - autoinducers (AIs) - into the environment. At the same time that bacterial population grows, the concentration of AIs in the bacterial environment increases. When a threshold concentration of AIs is reached, bacterial cells respond to it by altering their gene expression profile. AIs regulate gene expression as a function of cell population density. Phenotypes mediated by QS (QSphenotypes) include virulence factors, toxin production, antibiotic resistance and biofilm formation. In this work, two polymeric materials (linear polymers and molecularly imprinted nanoparticles) were developed and their ability to attenuate QS was evaluated. Both types of polymers should to be able to adsorb bacterial signal molecules, limiting their availability in the extracellular environment, with expected disruption of QS. Linear polymers were composed by one of two monomers (itaconic acid and methacrylic acid), which are known to possess strong interactions with the bacterial signal molecules. Molecularly imprinted polymer nanoparticles (MIP NPs) are particles with recognition capabilities for the analyte of interest. This ability is attained by including the target analyte at the synthesis stage. Vibrio fischeri and Aeromonas hydrophila were used as model species for the study. Both the linear polymers and MIP NPs, tested free in solutions and coated to surfaces, showed ability to disrupt QS by decreasing bioluminescence of V. fischeri and biofilm formation of A. hydrophila. No significant effect on bacterial growth was detected. The cytotoxicity of the two types of polymers to a fibroblast-like cell line (Vero cells) was also tested in order to evaluate their safety. The results showed that both the linear polymers and MIP NPs were not cytotoxic in the testing conditions. In conclusion, the results reported in this thesis, show that the polymers developed are a promising strategy to disrupt QS and reduce bacterial infection and resistance. In addition, due to their low toxicity, solubility and easy integration by surface coating, the polymers have potential for applications in scenarios where bacterial infection is a problem: medicine, pharmaceutical, food industry and in agriculture or aquaculture.

How Gene Patents May Inhibit Scientific Research

Commentaire / Commentary

Short terms effects of air pollution from biomass burning in mucociliary clearance of Brazilian sugarcane cutters

Nasal mucociliary system is the first line of defense of the upper airways and may be affected acutely by exposure to particulate matter (PM) from biomass burning. Several epidemiologic studies have demonstrated a consistent association between levels of air pollution from biomass burning with increases in hospitalization for respiratory diseases and mortality. To determine the acute effects of exposure to particulate matter from biomass burning in nasal mucociliary transport by saccharin transit time (STT) test, we studied thirty-three non-smokers and twelve light smokers sugarcane cutters in two periods: pre-harvest season and 4 h after harvest at the first day after biomass burning. Lung function, exhaled carbon monoxide (CO), nasal symptoms questionnaire and mucociliary clearance (MC) were assessed. Exhaled CO was increased in smokers compared to non-smokers but did not change significantly after harvest. In contrast, SIT was similar between smokers and non-smokers and decreased significantly after harvest in both groups (p < 0.001). Exposure to PM from biomass burning did not influence nasal symptoms. Our results suggest that acute exposure to particulate matter from sugarcane burned affects mucociliary clearance in smokers and non-smokers workers in the absence of symptoms. (C) 2011 Elsevier Ltd. All rights reserved.

Mentol como anestésico para dourado (Salminus brasiliensis)

Different levels of menthol as an anesthetic for dourado (Salminus brasiliensis) were evaluated in this study. Fish (n=32) with average weight of 194.13 +/- 9.06 g and total mean length of 25.30 +/- 0.90 cm were separated in four groups composed of 8 individuals. Each group was submitted to different menthol concentrations: 60, 90, 120 and 150 mg L(-1). Total induction time was analyzed by polynomial regression and other parameters by Tukey's test. All experimental fish exposed to different concentrations of menthol reached deep anesthesia stage without mortality. It was observed a negative linear effect (P<0.05) for total induction time. The longest recovery time (172.60 s) was observed for dourado treated with 120 mg. L(-1), which differed (P<0.05) from the 90 mg.L(-1) treatment (122.03 s). All levels evaluated in this study were safe and effective. A concentration of 60 mg L(-1) for dourado is suggested based on lower cost and adequate induction and recovery time responses.

Short terms effects of air pollution from biomass burning in mucociliary clearance of Brazilian sugarcane cutters

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fatores de risco associados à mortalidade de recém-nascidos de muito baixo peso na cidade de Botucatu, São Paulo, no período 1995-2000

OBJETIVOS: avaliar as práticas assistenciais, a ocorrência de doenças, a mortalidade durante a hospitalização e os fatores associados em recém-nascidos prematuros de muito baixo peso (PT-MBP). MÉTODOS: estudo transversal comparando dois períodos: 1995-1997 e 1998-2000 e envolvendo todos os PT-MBP nascidos vivos (n= 451), em um centro perinatal, em Botucatu, São Paulo, Brasil. Os fatores de risco pré-natal e pós-natal foram submetidos a análise multivariada. RESULTADOS: a mortalidade diminuiu de 36,2% para 29,5%. A sobrevida melhorou e foi superior a 50% a partir de 28 semanas e de 750 g de peso. O uso de corticosteróide antenatal aumentou de 25% para 42%, o surfactante exógeno de 14% para 28%, com redução na incidência e gravidade da síndrome do desconforto respiratório. A regressão logística mostrou que a síndrome do desconforto respiratório grave, Odds ratio=18, e a sepse precoce, Odds ratio=2,8, foram importantes fatores de risco para morte em 1995-1997. No período de 1998-2000, a sepse precoce e tardia, Odds ratio=10,5 e 12, respectivamente, aumentaram o risco de morte. CONCLUSÕES: a melhora na assistência perinatal diminuiu a mortalidade do PT-MBP. O aumento na exposição antenatal ao corticosteróide diminuiu a gravidade da síndrome do desconforto respiratório. em 1998-2000, a sepse foi o único fator de risco para morte.

Alterações morfológicas, apoptose e expressão de metaloproteinases no tecido laminar de equinos submetidos à obstrução intestinal experimental: efeitos da hidrocortisona

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Doença periodontal em pacientes com Diabetes Mellitus: influência de polimorfismos genéticos?

Currently it is clear that there are several factors that can act as modifiers of diseases, without causing them directly, but having the potential to make these conditions to progress faster and more severe. There is a growing number of studies investigating the relationship between Diabetes Mellitus (DM) and Periodontal Disease (PD), including some studies focusing on the influence of genetic factors in this process. The aim of this study was to verify through a literature review, the influence of genetic polymorphisms in the development of PD in patients with DM. PubMed and BIREME were used as databases and the terms Periodontitis or Periodontal Disease, Polymorphism, Diabetes Mellitus were searched. After a refinement in the literature, five studies were selected and they were related to chronic PD with DM and polymorphisms in cytokine genes, especially interleukin 1 (IL1) e IL6. Polymorphisms were associated with a higher concentration of pro-inflammatory cytokines in the gingival crevicular fluid of diabetic patients when compared to non-diabetic. In conclusion, it is necessary to confirm this association with longitudinal studies that must investigate a larger number of cytokine genes in order to understand the cause-effect relationship between genetic polymorphisms, DM and PD.

Prática de atividades físicas, doenças crônicas não transmissíveis e mortalidade entre adultos usuários da atenção primária do sistema público de saúde de Bauru, São Paulo: estudo longitudinal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease

Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

Living Invisible: HTLV-1-Infected Persons and the Lack of Care in Public Health

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is intractable and endemic in many countries. Although a few individuals have severe symptoms, most patients remain asymptomatic throughout their lives and their infections may be unknown to many health professionals. HTLV-1 can be considered a neglected public health problem and there are not many studies specifically on patients' needs and emotional experiences. Objective: To better understand how women and men living with HTLV-1 experience the disease and what issues exist in their healthcare processes. Methods: A qualitative study using participant observation and life story interview methods was conducted with 13 symptomatic and asymptomatic patients, at the outpatient clinic of the Emilio Ribas Infectious Diseases Institute, in Sao Paulo, Brazil. Results and Discussion: The interviewees stated that HTLV-1 is a largely unknown infection to society and health professionals. Counseling is rare, but when it occurs, focuses on the low probability of developing HTLV-1 related diseases without adequately addressing the risk of infection transmission or reproductive decisions. The diagnosis of HTLV-1 can remain a stigmatized secret as patients deny their situations. As a consequence, the disease remains invisible and there are potentially negative implications for patient self-care and the identification of infected relatives. This perception seems to be shared by some health professionals who do not appear to understand the importance of preventing new infections. Conclusions: Patients and medical staff referred that the main focus was the illness risk, but not the identification of infected relatives to prevent new infections. This biomedical model of care makes prevention difficult, contributes to the lack of care in public health for HTLV-1, and further perpetuates the infection among populations. Thus, HTLV-1 patients experience an "invisibility" of their complex demands and feel that their rights as citizens are ignored.

Política de saúde do homem

No artigo discute-se a articulação entre sistemas de informações epidemiológicas, produção científica e políticas de saúde de assistência à saúde do homem. Foram utilizadas três fontes secundárias: dados do Ministério da Saúde (Sistemas de Informação sobre Mortalidade e Hospitalar, Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico), artigos publicados na SciELO e documentos do Ministério da Saúde referentes à saúde do homem. Os resultados apontam que, em termos de morbimortalidade, os homens estão mais expostos a riscos do que as mulheres. Na produção científica, predominam estudos que focalizam os agravos e doenças exclusivamente masculinos em detrimento de outros aspectos relacionados à saúde. Documentos legais destacam o panorama epidemiológico de morbimortalidade masculina e a metodologia de elaboração da política. É necessário que os pesquisadores ampliem a utilização dos dados dos sistemas de informações epidemiológicas do Ministério da Saúde e procedam à incorporação crítica da perspectiva relacional de gênero.

Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer

BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome," defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. RESULTS: Caregivers had higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6 (beta =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

Gender and the relationship between traumatic childhood experiences and pain in adulthood

OBJECTIVES AND METHODS: Gender differences regarding 17 childhood experiences, thought to have traumatising potential (Traumatic Childhood Experiences = TCE), and pain behaviour in adulthood were assessed using a self-administered, anonymously filled-out questionnaire. Patients were consecutively accrued in the offices of practicing physicians. Three research questions were formulated: 1) Are specific TCE reported more frequently in male and female patients with the diagnosis "Pain Associated with Psychological Factors" (PP), compared to patients with "Pain, explained by Organic Processes" (OP), and "Patients with Diseases without Pain" (OD)? 2) Do PP-men and PP-women differ in reporting TCE?; 3) Are specific TCE correlated with Pain Duration, -Intensity and Number of Operations? RESULTS: 1). TCE occurred more frequently in PP-men and PP-women compared to OP- and OD-patients. 2). The PP-women reported much more TCE-items than the PP-men. 3). Duration and Intensity of adult pain associated with psychological factors correlated with certain TCE-items. CONCLUSIONS: The three research questions can be answered by "yes". In patients with pain which has been impossible to diagnose and/or has resisted conventional forms of therapy, TCE (verbal, physical and sexually abusive) have to be looked for, because they often explain adult pain. Unnecessary examinations and surgery can be avoided and therapies can be tailored for the individual patient.