Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy.

Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.

Methane adsorption and methanol desorption of copper modified boron silicate.

Boron silicate (BS) with a chabazite framework structure was synthesised using a direct route and rigorously characterized before it was ion-exchanged with copper to form Cu-BS. Employing in situ infrared spectroscopy, we show that Cu-BS is capable of oxidising methane to methoxy species and methanol interacts with the boron sites without deprotonation.

In Situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth.

Brushite cements are fast self-setting materials that can be used as bone substitute materials. Although tracing their fast setting process is a challenge, it is important for the understanding of the same, which in turn is important for the material's further development and use in the clinics. In this study, the setting rate, phase formation, and crystal growth of brushite cements were quantitatively studied by in situ synchrotron powder X-ray diffraction (SXRD) on a time scale of seconds. The influence of reactant ratios and a retardant (citric acid) on the setting reaction were analyzed. To complement the in situ investigations, scanning electron microscopy was carried out for ex situ morphological evolution of crystals. The initial reaction followed a four-step process, including a fast nucleation induction period, nucleation, crystal growth, and completion of the setting. The brushite crystal size grew up to the micro scale within 1 min, and the brushite content increased linearly after the nucleation until all monocalcium phosphate monohydrate (MCPM; Ca(H2PO4)2·H2O) had dissolved within minutes, followed by a slow increase until the end of the monitoring. By adjusting the MCPM to the ß-tricalcium phosphate (ß-TCP, ß-Ca3(PO4)2) ratio in the starting powders, the brushite/monetite ratio in the cements could be modified. In the presence of citric acid, the formation of brushite nuclei was not significantly retarded, whereas the increase in brushite content and the growth of crystal size were effectively hindered. The amount of monetite also increased by adding citric acid. This is the first time that the brushite setting process has been characterized in the first seconds and minutes of the reaction by SXRD.

Stability of monosodium glutamate in green table olives and pickled cucumbers as a function of packing conditions and storage time.

The effects of different packing conditions and storage times on the stability of monosodium glutamate (MSG) added to two different fermented vegetables (Spanish-type green table olives and pickled cucumbers) were studied. Factors such as packaging material (glass bottle versus plastic pouch), heat treatment (pasteurisation versus non-pasteurisation), and the presence or not of a preservative compound (potassium sorbate) were considered. The MSG content of pickled cucumbers was stable for up to 1 year of storage in all packing conditions studied. The MSG content also remained stable in pasteurised green table olives. On the contrary, MSG was extensively degraded (>75% degradation) after 54 weeks of storage in unpasteurised green olives with a higher degradation rate in glass bottles compared with plastic pouches. In the presence of potassium sorbate, MSG was also considerably degraded in olives packed in plastic pouches (>50% degradation), but hardly degraded in glass bottles. The results indicate that MSG degradation in olives is due to the action of both lactic acid bacteria and yeasts, with the formation of γ-aminobutyric acid as the major end-product.

Investigations into acrylamide precursors in sterilized table olives: evidence of a peptic fraction being responsible for acrylamide formation.

Formation of acrylamide from commercial model peptides containing protein-bound aspartic acid, alanine and methionine, respectively, at 200°C and different times in the absence of any carbonyl sources, was demonstrated by HPLC-MS/MS analyses. Further experiments using a more complex model system based on olive water, i.e., the aqueous fraction of olive pulp from untreated and lye-treated green olives, were performed. After partial fractionation of olive water by solid-phase extraction, only peptides/proteins containing fractions, being devoid of free asparagine, generated significant amounts of acrylamide during less harsh heat treatment (121°C for 30min). In contrast, acrylamide was not detected after heating the same fraction under identical thermal conditions when previously subjected to acid hydrolysis. Consistently, significant amounts of acrylamide were released after heating the albuminous precipitate resulting from acetone precipitation of olive water. These results strongly support the role of peptides/proteins as precursors of acrylamide formation in sterilized olives.

Degradation of ascorbic acid and potassium sorbate by different Lactobacillus species isolated from packed green olives.

The aim of this research was to ascertain the lactic acid bacteria responsible for the degradation of ascorbic acid and/or potassium sorbate, isolated from packed green olives where these additives had diminished. A total of 14 isolates were recovered from samples of different green olive containers. According to partial sequencing of the 16S rRNA coding gene, Lactobacillus parafarraginis, Lactobacillus rapi, Lactobacillus pentosus, Lactobacillus paracollinoides, and Pediococcus ethanolidurans were identified. With the exception of L. pentosus and L. paracollinoides, the other species had not been mentioned in table olives before this study. Only three of the 14 isolates metabolized ascorbic acid in MRS broth, and the products from ascorbic acid in modified MRS broth without carbon sources were acetic and lactic acids. Except for the two L. rapi and the two P. ethanolidurans strains, the remaining 10 isolates depleted potassium sorbate added into MRS broth to some extent. The product generated by three of these strains was confirmed to be trans-4-hexenoic acid. The degradation of ascorbate or sorbate by lactic acid bacteria should be taken into account when these additives are used in food products where this group of bacteria may be present.

Analysis of performance characteristics of five cell cycle-related immunohistochemical markers and human papillomavirus genotyping in the diagnosis of cervical squamous cell carcinoma precursor lesions.

OBJECTIVE: To study the performance values of a set of five immunohistochemical markers involved in cell cycle regulation as a potential aid in the differential diagnosis between squamous intraepithelial lesions (SILs) and normal or benign conditions of the uterine cervix. STUDY DESIGN: Results from immunohistochemical evaluation of p16, cyclin D1, p53, Ki67, and ProEx C markers and human papillomavirus genotyping were collected from a previous study performed on 37 normal or benign cervices, 39 low grade SILs and 73 high grade SILs. A multivariate analysis was used to examine the specific diagnostic value of each marker and to ascertain those most relevant for SIL diagnosis. For markers with good data fit, sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, and integrated discrimination improvement, were calculated. RESULTS: Among individual markers, ProEx C showed the best specificity; p16 displayed the highest sensitivity and area under receiver operating characteristic curve for SIL diagnosis. Integrated discrimination improvement demonstrated that the p16 plus ProEx C model has better discrimination capacity than p16 plus Ki67 or ProEx C plus Ki67. CONCLUSION: Use of ProEx C alone or in combination with p16 could provide useful information for SIL diagnosis.

Fermented vegetables containing benzoic and ascorbic acids as additives: benzene formation during storage and impact of additives on quality parameters.

Chemical and sensorial changes related to the use of benzoates and ascorbic acid as additives in packed fermented vegetables were investigated. For this, three selected vegetables (green olives, cucumbers, and caperberries) stored under different conditions (glass or plastic containers, ambient or refrigerated storage) were used. In all cases, benzoic acid remained unchanged (glass bottle) or decreased slightly (plastic pouch) at prolonged storage. Ascorbic acid was partially or totally degraded during storage, the degradation rate depending on the storage conditions and the vegetable matrix. Benzene levels higher than 10 µg/L were found in cucumbers and caperberries containing both additives, but only when packed in plastic pouches and after prolonged storage at room temperature. In these conditions, an appreciable browning of brine, related to AA degradation, was also found. The use of benzoate alone had a significant influence on vegetable color, but flavor was not significantly affected at the benzoate levels tested. On the basis of the present study, benzoates should be removed from fermented vegetable formulations containing ascorbic acid to eliminate possible benzene formation during long-term storage.

Dosimetric characterization of an 192Ir brachytherapy source with the Monte Carlo code PENELOPE.

Monte Carlo calculations are highly spread and settled practice to calculate brachytherapy sources dosimetric parameters. In this study, recommendations of the AAPM TG-43U1 report have been followed to characterize the Varisource VS2000 (192)Ir high dose rate source, provided by Varian Oncology Systems. In order to obtain dosimetric parameters for this source, Monte Carlo calculations with PENELOPE code have been carried out. TG-43 formalism parameters have been presented, i.e., air kerma strength, dose rate constant, radial dose function and anisotropy function. Besides, a 2D Cartesian coordinates dose rate in water table has been calculated. These quantities are compared to this source reference data, finding results in good agreement with them. The data in the present study complement published data in the next aspects: (i) TG-43U1 recommendations are followed regarding to phantom ambient conditions and to uncertainty analysis, including statistical (type A) and systematic (type B) contributions; (ii) PENELOPE code is benchmarked for this source; (iii) Monte Carlo calculation methodology differs from that usually published in the way to estimate absorbed dose, leaving out the track-length estimator; (iv) the results of the present work comply with the most recent AAPM and ESTRO physics committee recommendations about Monte Carlo techniques, in regards to dose rate uncertainty values and established differences between our results and reference data. The results stated in this paper provide a complete parameter collection, which can be used for dosimetric calculations as well as a means of comparison with other datasets from this source.

Genotype distribution of human papillomavirus (HPV) and co-infections in cervical cytologic specimens from two outpatient gynecological clinics in a region of southeast Spain.

BACKGROUND: Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical cytologic specimens from Murcia Region, (southeast Spain), to obtain information regarding the possible effect of the ongoing vaccination campaign against HPV16 and HPV18. METHODS: A total of 458 cytologic specimens were obtained from two outpatient gynecological clinics. These included 288 normal benign (N/B) specimens, 56 atypical squamous cell of undetermined significance (ASC-US), 75 low-grade squamous intraepithelial lesions (LSIL) and 39 high-grade squamous intraepithelial lesions (HSIL). HPV genotyping was performed using PCR and tube array hybridization. RESULTS: The most frequent genotype found was HPV16 (14.9% in N/B; 17.9% in ASC-US; 29.3% in LSIL and 33.3% HSIL). Distribution of other genotypes was heavily dependent on the cytologic diagnoses. Co-infections were found in 15.3% of N/B, 10.7% of ASC-US, 48% of LSIL and 25.6% of HSIL cases (significantly different at p < 0.001). Strikingly, in N/B diagnoses, genotypes from A5 species were found as coinfecting in all cases. Genotypes from A7 or A9 species appeared in co-infections in 56.5% and 54% respectively whereas genotypes from A6 species appeared in 25.1% of cases. CONCLUSION: HPV vaccination might prevent 34.6% and 35.8% of LSIL and HSIL, respectively. Co-infection rate is dependent on both cytologic diagnosis and HPV genotype. Moreover, genotypes belonging to A5, A7 and A9 species are more often found as co-infections than genotype pertaining to A6 species. This suggests that phylogenetically related genotypes might have in common similar grades of dependency for cervical epithelium colonization.

D-amino acid formation in sterilized alkali-treated olives.

The occurrence of d-amino acids in commercial ripe olives, a well-known sterilized alkali-treated product, was investigated by high-performance liquid chromatography (HPLC) with precolumn automatic derivatization. Absolute amounts of D-amino acids were in total 18.6-38.2 mg/100 g edible portion. The major D-amino acids were D-aspartic acid, D-glutamic acid, D-serine, and D-leucine. Furthermore, to evaluate the effects of sterilization time and olive pH on amino acid racemization, a simulated processing of green ripe olives was carried out. Serine (both free and bound form) was the most-racemized amino acid after heat treatment. Sterilization (15-35 min at 121 degrees C) increased the racemization values of both free and protein-bound amino acids, although in case of protein-bound phenylalanine the increase was not statistically significant. With an increase of pH from 8 to 10 units, the racemization values of all amino acids increased significantly, except for free forms of aspartic and glutamic acids. In general, the effects of the sterilization time and olive pH on total concentration (L + D enantiomers) of each amino acid were also significant.

Vitamin content and amino acid composition of pickled garlic processed with and without fermentation.

The effect of processing, with and without fermentation, upon the nutritional composition of pickled garlic was evaluated. On a dry basis, the fermented product had a higher content of riboflavin, alpha-tocopherol, and most individual amino acids but a lower thiamin level than the unfermented product. Ascorbic acid was totally lost during processing. The chemical scores for the unfermented and fermented product were 88 and 108%, respectively, with the limiting amino acid being leucine. Water blanching (90 degrees C for 4 min) affected only the ascorbic acid content, whereas fermentation significantly affected the contents of thiamin, ascorbic acid, and alpha-tocopherol, as well as glutamic acid and arginine. For each processing type, the effect of the preservation method and storage time on vitamins and amino acid composition was also analyzed. In the case of the fermented product, usage of the corresponding fermentation brine plus refrigerated storage was also assayed as the packing/preservation method and was found to give the best result from a nutritional standpoint.

Electrophysiological characterization of the human Na(+)/nucleoside cotransporter 1 (hCNT1) and role of adenosine on hCNT1 function.

We previously reported that the human Na(+)/nucleoside transporter pyrimidine-preferring 1 (hCNT1) is electrogenic and transports gemcitabine and 5'-deoxy-5-fluorouridine, a precursor of the active drug 5-fluorouracil. Nevertheless, a complete electrophysiological characterization of the basic properties of hCNT1-mediated translocation has not been performed yet, and the exact role of adenosine in hCNT1 function has not been addressed either. In the present work we have used the two-electrode voltage clamp technique to investigate hCNT1 transport mechanism and study the kinetic properties of adenosine as an inhibitor of hCNT1. We show that hCNT1 exhibits presteady-state currents that disappear upon the addition of adenosine or uridine. Adenosine, a purine nucleoside described as a substrate of the pyrimidine-preferring transporters, is not a substrate of hCNT1 but a high affinity blocker able to inhibit uridine-induced inward currents, the Na(+)-leak currents, and the presteady-state currents, with a K(i) of 6.5 microM. The kinetic parameters for uridine, gemcitabine, and 5'-deoxy-5-fluorouridine were studied as a function of membrane potential; at -50 mV, K(0.5) was 37, 18, and 245 microM, respectively, and remained voltage-independent. I(max) for gemcitabine was voltage-independent and accounts for approximately 40% that for uridine at -50 mV. Maximal current for 5'-DFUR was voltage-dependent and was approximately 150% that for uridine at all membrane potentials. K(0.5)(Na(+)) for Na(+) was voltage-independent at hyperpolarized membrane potentials (1.2 mM at -50 mV), whereas I(max)(Na(+)) was voltage-dependent, increasing 2-fold from -50 to -150 mV. Direct measurements of (3)H-nucleoside or (22)Na fluxes with the charge-associated revealed a ratio of two positive inward charges per nucleoside and one Na(+) per positive inward charge, suggesting a stoichiometry of two Na(+)/nucleoside.