Abstract
Mucins are large glycoproteins consisting of approximately 80% of hetero-oligosaccharides. Gut mucin degraders of healthy subjects were investigated, through a culture dependent and ...independent approach. The faeces of five healthy adults were subjected to three steps of anaerobic enrichment in a medium with sole mucins as carbon and nitrogen sources. The bacterial community was compared before and after the enrichment by 16S rRNA gene profiling. Bacteria capable of fermenting sugars, such as
Anaerotruncus
,
Holdemania,
and Enterococcaceae likely took advantage of the carbohydrate chains.
Escherichia coli
and Enterobacteriaceae, Peptococcales, the Coriobacteriale
Eggerthella
, and a variety of Clostridia such as Oscillospiraceae,
Anaerotruncus
, and
Lachnoclostridium
, significantly increased and likely participated to the degradation of the protein backbone of mucin. The affinity of
E. coli
and Enterobacteriaceae for mucin may facilitate the access to the gut mucosa, promoting gut barrier damage and triggering systemic inflammatory responses. Only three species of strict anaerobes able to grow on mucin were isolated from the enrichments of five different microbiota:
Clostridium disporicum
,
Clostridium tertium
, and
Paraclostridium benzoelyticum
. The limited number of species isolated confirms that in the gut the degradation of these glycoproteins results from cooperation and cross-feeding among several species exhibiting different metabolic capabilities.
Folate production by probiotic bacteria Rossi, Maddalena; Amaretti, Alberto; Raimondi, Stefano
Nutrients,
01/2011, Letnik:
3, Številka:
1
Journal Article, Book Review
Recenzirano
Odprti dostop
Probiotic bacteria, mostly belonging to the genera Lactobacillus and Bifidobacterium, confer a number of health benefits to the host, including vitamin production. With the aim to produce ...folate-enriched fermented products and/or develop probiotic supplements that accomplish folate biosynthesis in vivo within the colon, bifidobacteria and lactobacilli have been extensively studied for their capability to produce this vitamin. On the basis of physiological studies and genome analysis, wild-type lactobacilli cannot synthesize folate, generally require it for growth, and provide a negative contribution to folate levels in fermented dairy products. Lactobacillus plantarum constitutes an exception among lactobacilli, since it is capable of folate production in presence of para-aminobenzoic acid (pABA) and deserves to be used in animal trials to validate its ability to produce the vitamin in vivo. On the other hand, several folate-producing strains have been selected within the genus Bifidobacterium, with a great variability in the extent of vitamin released in the medium. Most of them belong to the species B. adolescentis and B. pseudocatenulatum, but few folate producing strains are found in the other species as well. Rats fed a probiotic formulation of folate-producing bifidobacteria exhibited increased plasma folate level, confirming that the vitamin is produced in vivo and absorbed. In a human trial, the same supplement raised folate concentration in feces. The use of folate-producing probiotic strains can be regarded as a new perspective in the specific use of probiotics. They could more efficiently confer protection against inflammation and cancer, both exerting the beneficial effects of probiotics and preventing the folate deficiency that is associated with premalignant changes in the colonic epithelia.
Abstract Background and purpose To determine a dose–effect relation for radiation induced rib fractures after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer ...(NSCLC). Automatic rib delineation has enabled the analysis of a large patient group. Material and methods Four-hundred and sixty-six patients with stage I/II NSCLC received SBRT with a median of 54 Gy in 3 fractions. The optimal EQD2-corrected dose parameter to predict (a)symptomatic fractures was found using Cox regression. Three normal tissue complication probability (NTCP) models based on this optimal parameter were constructed: (1) at a median follow up (FU) of 26 months, (2) for all data, with time to toxicity taken into account and (3) at a FU of 26 months, excluding low dose ribs. Results The median time to fracture was 22 (range 5–51) months. Maximum rib dose best predicted fractures. The TD50 (dose with 50% complication) of the second NTCP model was 375 Gy. The TD50 was significantly higher for the other models indicating an under-estimation of the dose effect at the median follow-up time and/or when excluding low dose ribs. Conclusions The risk of symptomatic rib fractures after SBRT was significantly correlated to dose, and was <5% at 26 months when Dmax < 225 Gy.
To discuss planning target volumes (PTVs) based on internal target volume (PTVITV), exhale-gated radiotherapy (PTVGating), and a new proposed midposition (PTVMidP; time-weighted mean tumor position) ...and compare them with the conventional free-breathing CT scan PTV (PTVConv).
Respiratory motion induces systematic and random geometric uncertainties. Their contribution to the clinical target volume (CTV)-to-PTV margins differs for each PTV approach. The uncertainty margins were calculated using a dose-probability-based margin recipe (based on patient statistics). Tumor motion in four-dimensional CT scans was determined using a local rigid registration of the tumor. Geometric uncertainties for interfractional setup errors and tumor baseline variation were included. For PTVGating, the residual motion within a 30% gating (time) window was determined. The concepts were evaluated in terms of required CTV-to-PTV margin and PTV volume for 45 patients.
Over the patient group, the PTVITV was on average larger (+6%) and the PTVGating and PTVMidP smaller (-10%) than the PTVConv using an off-line (bony anatomy) setup correction protocol. With an on-line (soft tissue) protocol the differences in PTV compared with PTVConv were +33%, -4%, and 0, respectively.
The internal target volume method resulted in a significantly larger PTV than conventional CT scanning. The exhale-gated and mid-position approaches were comparable in terms of PTV. However, mid-position (or mid-ventilation) is easier to use in the clinic because it only affects the planning part of treatment and not the delivery.
Thirty-four strains of lactic acid bacteria (seven
Bifidobacterium
, 11
Lactobacillus
, six
Lactococcus
, and 10
Streptococcus thermophilus
) were assayed in vitro for antioxidant activity against ...ascorbic and linolenic acid oxidation (TAA
AA
and TAA
LA
), trolox-equivalent antioxidant capacity (TEAC), intracellular glutathione (TGSH), and superoxide dismutase (SOD). Wide dispersion of each of TAA
AA
, TAA
LA
, TEAC, TGSH, and SOD occurred within bacterial groups, indicating that antioxidative properties are strain specific. The strains
Bifidobacterium animalis
subsp.
lactis
DSMZ 23032,
Lactobacillus acidophilus
DSMZ 23033, and
Lactobacillus brevis
DSMZ 23034 exhibited among the highest TAA
AA
, TAA
LA
, TEAC, and TGSH values within the lactobacilli and bifidobacteria. These strains were used to prepare a potentially antioxidative probiotic formulation, which was administered to rats at the dose of 10
7
, 10
8
, and 10
9
cfu/day for 18 days. The probiotic strains colonized the colon of the rats during the trial and promoted intestinal saccharolytic metabolism. The analysis of plasma antioxidant activity, reactive oxygen molecules level, and glutathione concentration, revealed that, when administered at doses of at least 10
8
cfu/day, the antioxidant mixture effectively reduced doxorubicin-induced oxidative stress. Probiotic strains which are capable to limit excessive amounts of reactive radicals in vivo may contribute to prevent and control several diseases associated with oxidative stress.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, EMUNI, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK
Stereotactic body radiation therapy (SBRT) for early-stage inoperable non-small cell lung cancer (NSCLC) patients delivers high doses that require high-precision treatment. Typically, image guidance ...is used to minimize day-to-day target displacement, but intrafraction position variability is often not corrected. Currently, volumetric modulated arc therapy (VMAT) is replacing intensity modulated radiation therapy (IMRT) in many departments because of its shorter delivery time. This study aimed to evaluate whether intrafraction variation in VMAT patients is reduced in comparison with patients treated with IMRT.
NSCLC patients (197 IMRT and 112 VMAT) treated with a frameless SBRT technique to a prescribed dose of 3 × 18 Gy were evaluated. Image guidance for both techniques was identical: pretreatment cone beam computed tomography (CBCT) (CBCTprecorr) for setup correction followed immediately before treatment by postcorrection CBCT (CBCTpostcorr) for verification. Then, after either a noncoplanar IMRT technique or a VMAT technique, a posttreatment (CBCTpostRT) scan was acquired. The CBCTpostRT and CBCTpostcorr scans were then used to evaluate intrafraction motion. Treatment delivery times, systematic (Σ) and random (σ) intrafraction variations, and associated planning target volume (PTV) margins were calculated.
The median treatment delivery time was significantly reduced by 20 minutes (range, 32-12 minutes) using VMAT compared with noncoplanar IMRT. Intrafraction tumor motion was significantly larger for IMRT in all directions up to 0.5 mm systematic (Σ) and 0.7 mm random (σ). The required PTV margins for IMRT and VMAT differed by less than 0.3 mm.
VMAT-based SBRT for NSCLC was associated with significantly shorter delivery times and correspondingly smaller intrafraction motion compared with noncoplanar IMRT. However, the impact on the required PTV margin was small.
Four-dimensional (4D) respiration-correlated imaging techniques can be used to obtain (respiration) artifact-free computed tomography (CT) images of the thorax. Current radiotherapy planning systems, ...however, do not accommodate 4D-CT data. The purpose of this study was to develop a simple, new concept to incorporate patient-specific motion information, using 4D-CT scans, in the radiotherapy planning process of lung cancer patients to enable smaller error margins.
A single CT scan was selected from the 4D-CT data set. This scan represented the tumor in its time-averaged position over the respiratory cycle (the mid-ventilation CT scan). To select the appropriate CT scan, two methods were used. First, the three-dimensional tumor motion was analyzed semiautomatically to calculate the mean tumor position and the corresponding respiration phase. An alternative automated method was developed to select the correct CT scan using the diaphragm motion.
Owing to hysteresis, mid-ventilation selection using the three-dimensional tumor motion had a tumor position accuracy (with respect to the mean tumor position) better than 1.1 +/- 1.1 mm for all three directions (inhalation and exhalation). The accuracy in the diaphragm motion method was better than 1.1 +/- 1.1 mm. Conventional free-breathing CT scanning had an accuracy better than 0 +/- 3.9 mm. The mid-ventilation concept can result in an average irradiated volume reduction of 20% for tumors with a diameter of 40 mm.
Tumor motion and the diaphragm motion method can be used to select the (artifact-free) mid-ventilation CT scan, enabling a significant reduction of the irradiated volume.
To quantify the localization accuracy and intrafraction stability of lung cancer patients treated with frameless, four-dimensional (4D) cone beam computed tomography (CBCT)-guided stereotactic body ...radiotherapy (SBRT) and to calculate and validate planning target volume (PTV) margins to account for the residual geometric uncertainties.
Sixty-five patients with small peripheral lung tumors were treated with SBRT without a body frame to 54 Gy in three fractions. For each fraction, three 4D-CBCT scans were acquired: before treatment to measure and correct the time-weighted mean tumor position, after correction to validate the correction applied, and after treatment to estimate the intrafraction stability. Patient-specific PTV margins were computed and subsequently validated using Monte Carlo error simulations.
Systematic tumor localization inaccuracies (1 SD) were 0.8, 0.8, and 0.9 mm for the left-right, craniocaudal, and anteroposterior direction, respectively. Random localization inaccuracies were 1.1, 1.1, and 1.4 mm. Baseline variations were 1.8, 2.9, and 3.0 mm (systematic) and 1.1, 1.5, and 2.0 mm (random), indicating the importance of image guidance. Intrafraction stability of the target was 1.2, 1.2, and 1.8 mm (systematic) and 1.3, 1.5, and 1.8 mm (random). Monte Carlo error simulations showed that patient-specific PTV margins (5.8-10.5 mm) were adequate for 94% of the evaluated cases (2-28 mm peak-to-peak breathing amplitude).
Frameless SBRT can be safely administered using 4D-CBCT guidance. Even with considerable breathing motion, the PTV margins can safely be kept small, allowing patients with larger tumors to benefit from the advantages of SBRT. In case bony anatomy would be used as a surrogate for tumor position, considerably larger PTV margins would be required.
Flavonols and flavanones are polyphenols exerting many healthy biological activities. They are often glycosylated by rutinose, which hampers absorption in the small intestine. Therefore they require ...the gut microbiota to release the aglycone and enable colonic absorption. The role of the gut microbiota and bifidobacteria in the release of the aglycones from two major rutinosides, hesperidin and rutin, was investigated. In bioconversion experiments, the microbiota removed rutinose from both rutin and hesperidin, even though complete hydrolysis was not obtained. To investigate whether bifidobacteria can participate to the hydrolysis of rutinosides, 33 strains were screened. Rutin was resistant to hydrolysis by all the strains. Among six tested species, mostly Bifidobacterium catenulatum and Bifidobacterium pseudocatenultum were able to hydrolyze hesperidin, by means of a cell-associated activity. This result is in agreement with the presence of a putative α-l-rhamnosidase in the genome of B. pseudocatenulatum, while most of the available genome sequences of bifidobacteria aside from this species do not bear this sequence. Even though B. pseudocatenulatum may contribute to the release of the aglycone from certain rutinose-conjugated polyphenols, such as hesperidin, it remains to be clarified whether this species may exert a role in affecting the bioavailability of the rutinoside in vivo.
Association of heart dose and overall survival was investigated in a cohort including 469 locally-advanced NSCLC patients receiving daily low-dose hypofractionated chemo-radiotherapy. Significant ...associations were found over a range of dose parameters. Multivariate analysis showed significant associations of heart_V2Gy:HR=1.007%−1 (95% CI:1.002–1.013; p=0.006), age:HR=1.026year−1 (1.011–1.042; p=0.001) and GTV volume:HR=1.001cc−1 (1.000–1.002; p=0.006) with overall survival.
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