Tumor aggressiveness is associated with cell integrity changes in breast cancer-surviving women: a follow-up study / La agresividad tumoral está asociada a las alteraciones de la integridad celular en las mujeres que sobreviven al cáncer de mama: estudio de seguimiento

Introduction: cell integrity and fat mass had been studied as a prognostic marker for cancer survival. Objective: our aim was to evaluate the association between tumor aggressiveness and cell integrity changes and adiposity in breast cancer (BC) survivors. Methods: women with BC (n = 114) were evaluated at diagnosis and 5 years later. Percentage of lean mass, fat mass, phase angle (PA), resistance (R) and reactance (Xc) were obtained by bioimpedance (450-50 kHz). Plasma leptin was assessed by immunoassay. Changes in body composition were assessed by the paired t-test or Wilcoxon's test. The disease effect associated with the time of diagnosis was assessed by a generalized linear model. Regression models were structured to assess the prevalence ratio between tumor aggressiveness and body composition changes adjusted for age, income, and level of schooling. Results: patients with N+ (p = 0.02) and % Ki67 > 14 (p = 0.00) show a reduction in Xc. Patients with advanced clinical staging (CS) (p = 0.02), tumors > 2 cm (p = 0.01), N+ (p = 0.01), non-luminal tumors (p = 0.02), ER- (p = 0, 00) and PR- (p = 0.02) show a PA reduction, and N+ patients (p = 0.01) show a reduction in leptin during follow-up. Tumors ≤ 2 cm (CI: 0.33-0.95; p = 0.03), initial CS (CI: 0.20-0.93; p = .0.03), and luminal tumors (CI: 0.01-0.95; p = 0.04) are related to a lower reduction in PA. Initial CS (CI: 0.00-0.00; p = 0.00) are related to increased leptin. Conclusion: tumor aggressiveness is associated with cell integrity changes in women who are BC survivors (AU)

Introducción: se han estudiado la integridad celular y la masa grasa como marcadores pronósticos de supervivencia al cáncer. Objetivo: nuestro objetivo fue evaluar la asociación entre la agresividad del tumor y los cambios en la integridad celular y la adiposidad en supervivientes de cáncer de mama (CM). Métodos: las mujeres con CM (n = 114) se evaluaron al diagnóstico y 5 años después. El porcentaje de masa magra, masa grasa, ángulo de fase (PA), resistencia (R) y reactancia (Xc) se obtuvo mediante bioimpedancia (450-50 kHz). La leptina plasmática se evaluó mediante inmunoensayo. Los cambios en la composición corporal se evaluaron mediante la prueba de la t pareada o la prueba de Wilcoxon. El efecto de la enfermedad asociado con el momento del diagnóstico se evaluó mediante un modelo lineal generalizado. Los modelos de regresión se estructuraron para evaluar la razón de prevalencia entre la agresividad del tumor y los cambios en la composición corporal ajustados por edad, ingresos y nivel de escolaridad. Resultados: las pacientes con N+ (p = 0,02) y % Ki67 > 14 (p = 0,00) muestran una reducción de Xc. Las pacientes con estadificación clínica (EC) avanzada (p = 0,02), tumores > 2 cm (p = 0,01), N+ (p = 0,01), tumores no luminales (p = 0,02), ER- (p = 0, 00) y PR- (p = 0,02) muestran una reducción de la AP, y los pacientes N+ (p = 0,01) muestran una reducción de la leptina durante el seguimiento. Los tumores ≤ 2 cm (IC: 0,33-0,95; p = 0,03), el EC inicial (IC: 0,20-0,93; p = 0,03) y los tumores luminales (IC: 0,01-0,95; p = 0,04) se relacionan con un menor reducción de la PA. Los EC iniciales (IC: 0,00-0,00; p = 0,00) están relacionados con un aumento de leptina. Conclusión: la agresividad del tumor se asocia con cambios en la integridad celular en las mujeres que sobreviven al CM (AU)

Factors affecting the exposure to physicochemical and microbiological pollutants in vehicle cabins while commuting in Lisbon.

Commuters are exposed to a variety of physicochemical and microbiological pollutants that can lead to adverse health effects. This study aims to evaluate the indoor air quality (IAQ) in cars, buses and trains in Lisbon, to estimate inhaled doses while commuting and to evaluate the impacts of cleaning and ventilation on the IAQ. Particulate matter with diameter lower than 1, 2.5 and 10 µm (PM1, PM2.5 and PM10), black carbon (BC), carbon monoxide (CO), carbon dioxide (CO2) volatile organic compounds (VOCs), formaldehyde (CH2O) and total airborne bacteria and fungi were measured and bacterial isolates were identified. Results showed that the type of ventilation is the main factor affecting the IAQ in vehicle cabins. Under the fan off condition, the concentration of BC was lower, but the concentration of gases such as CO2, CO and VOC tended to accumulate rapidly. When the ventilation was used, the coarse particles were filtered originating the decrease of indoor concentrations. Commuters travelling in trains received the lowest dose for all chemical pollutants, except VOC, mainly because railways are further away from the direct vehicular emissions. Commuters travelling in cars without ventilation received the highest inhaled dose for almost all pollutants despite having the lowest travel duration. Airborne microbiota was highly affected by the occupancy of the vehicles and therefore, the fungi and bacterial loads were higher in trains and buses. Most of the isolated species were human associated bacteria and some of the most abundant species have been linked to respiratory tract infections.

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis.

Coinfection with leishmaniasis and schistosomiasis has been associated with increased time to healing of cutaneous lesions of leishmaniasis. The objective of this study was to evaluate the effect of Leishmania braziliensis infection on co-cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes from patients with schistosomiasis and patients with cutaneous leishmaniasis. MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic beads, infected with L. braziliensis, and co-cultured with autologous lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10 receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on lymphocytes were evaluated by flow cytometry. The production of the cytokines IL-10, TNF, IL-12p40, and IFN-γ were evaluated by sandwich ELISA of the culture supernatant. The infectivity evaluation was performed by light microscopy after concentration of cells by cytospin and Giemsa staining. It was observed that the frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR were smaller in the group of patients with schistosomiasis compared to the group of patients with leishmaniasis. On the other hand, the frequency of IL-10R on MoDCs was higher in patients with schistosomiasis than in patients with leishmaniasis. CD4+ and CD8+ T lymphocytes from patients with schistosomiasis presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the supernatants of co-cultures from individuals with schistosomiasis compared to those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-γ were lower in the group of individuals with schistosomiasis. Regarding the frequency of MoDCs infected by L. braziliensis after 72h in culture, it was observed that higher frequencies of cells from patients with schistosomiasis were infected compared to cells from patients with leishmaniasis. It was concluded that MoDCs from patients with schistosomiasis are more likely to be infected by L. braziliensis, possibly due to a lower degree of activation and a regulatory profile.

High frequencies of antibiotic resistance genes in infants' meconium and early fecal samples.

The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to ß-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies' mothers, as well as a mother-infant series including meconium, fecal samples collected through the infant's 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds' samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant's GIT as a noteworthy reservoir of this gene.

Association of oxidative stress biomarkers with adiposity and clinical staging in women with breast cancer.

BACKGROUND/OBJECTIVES: Breast cancer is a disease characterised by both oxidative reactions and inflammation. However, few studies have focused on the oxidative and inflammatory biomarkers. The aim of the present study was to evaluate the association between oxidative stress markers and adiposity and clinical staging, as well as the association between the oxidative and the antioxidant biomarkers of women with breast cancer. SUBJECTS/METHODS: A total of 135 cases of breast cancer occurring in 2011 and 2012 were assessed. After exclusions, 101 pre- and post-menopausal women with clinical staging I to IV were eligible to participate in the study. The anthropometric evaluation was performed by collecting data on waist circumference, body mass index and body composition. The socioeconomic and clinical profiles were determined using a standard questionnaire. For the oxidative biomarkers, thiobarbituric acid reactive substances (TBARS), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), low-density lipoprotein(-) (LDL(-)), autoantibody anti-LDL(-) and liposoluble antioxidants (α-tocopherol, retinol and ß-carotene) were analysed. The data were analysed using differences in the mean values, correlation tests and multiple linear regression. RESULTS: The antioxidant levels were higher in postmenopausal women with clinical staging I and II and negative lymph nodes. The TBARS level was associated with clinical staging. Adiposity was associated with levels of retinol and 8-OHdG, whereas LDL(-), 8-OHdG and TBARS were correlated with liposoluble antioxidants after adjusting for the confounders. CONCLUSIONS: The adiposity and clinical staging of patients were associated with oxidative stress. The oxidative and antioxidant biomarkers showed a negative correlation in patients with breast cancer.

Effects of gamma radiation on raspberries: safety and quality issues.

There is an ever-increasing global demand from consumers for high-quality foods with major emphasis placed on quality and safety attributes. One of the main demands that consumers display is for minimally processed, high-nutrition/low-energy natural foods with no or minimal chemical preservatives. The nutritional value of raspberry fruit is widely recognized. In particular, red raspberries are known to demonstrate a strong antioxidant capacity that might prove beneficial to human health by preventing free radical-induced oxidative stress. However, food products that are consumed raw, are increasingly being recognized as important vehicles for transmission of human pathogens. Food irradiation is one of the few technologies that address both food quality and safety by virtue of its ability to control spoilage and foodborne pathogenic microorganisms without significantly affecting sensory or other organoleptic attributes of the food. Food irradiation is well established as a physical, nonthermal treatment (cold pasteurization) that processes foods at or nearly at ambient temperature in the final packaging, reducing the possibility of cross contamination until the food is actually used by the consumer. The aim of this study was to evaluate effects of gamma radiation on raspberries in order to assess consequences of irradiation. Freshly packed raspberries (Rubus idaeus L.) were irradiated in a (60)Co source at several doses (0.5, 1, or 1.5 kGy). Bioburden, total phenolic content, antioxidant activity, physicochemical properties such as texture, color, pH, soluble solids content, and acidity, and sensorial parameters were assessed before and after irradiation and during storage time up to 14 d at 4°C. Characterization of raspberries microbiota showed an average bioburden value of 10(4) colony-forming units (CFU)/g and a diverse microbial population predominantly composed of two morphological types (gram-negative, oxidase-negative rods, 35%, and filamentous fungi, 41%). The inactivation studies on the raspberries mesophilic population indicated a one log reduction of microbial load (95% inactivation efficiency for 1.5 kGy), in the surviving population mainly constituted by filamentous fungi (79-98%). The total phenolic content of raspberries indicated an increase with radiation doses and a decrease with storage time. The same trend was found for raspberries' antioxidant capacity with storage time. Regarding raspberries physicochemical properties, irradiation induced a significant decrease in firmness compared with nonirradiated fruit. However, nonirradiated and irradiated fruit presented similar physicochemical and sensory properties during storage time. Further studies are needed to elucidate the benefits of irradiation as a raspberries treatment process.

Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives.

Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.

Seasonal evaluation of outdoor/indoor air quality in primary schools in Lisbon.

The aim of this study was to evaluate the indoor (I) and outdoor (O) levels of NO2, speciated volatile organic compounds (VOCs) and carbonyls at fourteen primary schools in Lisbon (Portugal) during spring, autumn and winter. Three of these schools were also selected to be monitored for comfort parameters, such as temperature and relative humidity, carbon dioxide (CO2), carbon monoxide (CO), total VOCs, and both bacterial and fungal colony-forming units per cubic metre. The concentration of CO2 and bioaerosols greatly exceeded the acceptable maximum values of 1800 mg m⁻³ and 500 CFU m⁻³, respectively, in all seasons. Most of the assessed VOCs and carbonyls occurred at I/O ratios above unity in all seasons, thus showing the importance of indoor sources and building conditions in indoor air quality. However, it has been observed that higher indoor VOC concentrations occurred more often in the colder months, while carbonyl concentrations were higher in the warm months. In general, the I/O NO2 ratios ranged between 0.35 and 1, never exceeding the unity. Some actions are suggested to improve the indoor air quality in Lisbon primary schools.

Questionable efficacy of plasma exchange for thrombotic thrombocytopenic purpura after bone marrow transplantation.

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) is an uncommon complication presumably associated with extensive endothelial cell damage due to Cyclosporine, total body irradiation, or other drugs. While the majority of patients with primary TTP, which is considered to be an autoimmune process, respond to plasma exchange, TTP after BMT has a very poor prognosis. A total of 7 patients out of 307 patients who underwent BMT were diagnosed with TTP during 1989-1999. The diagnosis of TTP was made based on thrombocytopenia and microhemangiopathic hemolytic anemia characterized by an elevated LDH and the presence of schistocytes on the peripheral blood smear. Five patients were treated with plasma exchange (PE) using fresh frozen plasma and/or cryoprecipitate poor plasma as replacement fluid. One patient was treated using a protein A column. One patient did not receive plasma exchange because the 125 patient was clinically stable and was discharged. It was hard to assess the efficacy of PE due to the multiplicity of the patients' clinical condition and laboratory data. At least 4 patients did not respond to PE and 2 patients were not able to be evaluated due to multi organ failure. However, all patients died. It is not clear at this moment if PE for patients with TTP after BMT is truly beneficial.

Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors.

Subinhibitory concentrations of bacitracin, vancomycin and other inhibitors of cell wall synthesis reversed to varying extents the intrinsic resistance of Mycobacterium tuberculosis to clarithromycin. Ethambutol reversed clarithromycin resistance in all of the M. tuberculosis strains studied regardless of their susceptibility to this drug.

6a,7-Dehydro-N-formylnornantenine and other constituents from Aristolochia brevipes.

From the non-coloured fraction of rhizomes of Aristolochia brevipes (Aristolochiaceae) the new aporphine alkaloid 6a,7-dehydro- N-formylnornantenine was isolated besides N-formylnornantenine, cadalene, and 4-hydroxy-4,7-dimethyl-1-tetralone.

The value of plasma prolactin levels in the prediction of the responsiveness of growth hormone secretion to bromocriptine and TRH in acromegaly.

UNLABELLED: The mechanism of the inhibition of growth hormone secretion in response to bromocriptine and the ability of thyrotropin releasing hormone to stimulate growth secretion in acromegaly is unknown. In the present study the relationship between the plasma prolactin concentration of untreated acromegalic patients and the reaction of growth hormone to thyrotropin releasing hormone and bromocriptine was investigated. Plasma prolactin levels were elevated in thirty-three (42%) of seventy-nine untreated acromegalic patients. Seventeen patients had mildly elevated prolactin levels, but in sixteen the plasma prolactin concentration was higher than 30 ng/ml. Bromocriptine (2.5 mg) inhibited growth hormone secretion by more than 50% in 22% of the normoprolactinaemic, in 53% of the mild hyperprolactinaemic and in 88% of the patients with a prolactin level above 30 ng/ml (P less than 0.01 v. normoprolactinaemic; P less than 0.01 v. mildly elevated prolactin levels). An increase of growth hormone secretion by more than 100% of the basal value in response to thyrotropin releasing hormone was observed in 44% of the normoprolactinaemic, in 59% of the mildly hyperprolactinaemic and in 75% of the clearly hyperprolactinaemic patients; (P less than 0.01 v. normo- and mildly hyperprolactinaemic patients). CONCLUSION: An increased plasma prolactin concentration in patients with acromegaly is accompanied in most patients by a higher sensitivity of growth hormone secretion to bromocriptine.