182 research outputs found
Impact of endostatin gene therapy on myeloid-derived suppressor cells from a metastatic renal cell carcinoma
Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b⁺Gr⁻1⁺ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b⁺Gr⁻1⁺ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b⁺Gr⁻1⁺ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b⁺Gr⁻1⁺ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment
Evaluation of antibiotic susceptibility of Lactobacillus plantarum isolated from traditional Portuguese sausage products
Nowadays the use of fermentative microbiota in food products is researched in order to confer protection to the products and furnish health benefits to consumers The aim of this work was to evaluate antibiotics susceptibility of Lactobacillus plantarum isolated from fermented traditional meat products in order to select them to be used as starters or protective bacteria on fermented meat products. The susceptibility of different L. plantarum isolates (n=44) from fermented/dry/smoked meat products of three different Portuguese industries were tested by Agar disc diffusion method for Vancomycin, Quinupristin/Dalfopristin, Rifampicin, Penicillin G, Erythromycine, Tetracycline, Gentamicin, Lincomycin and Chloramphenicol. Most of the studied L plantarum isolates were susceptible for Tetracycline (75%) and Erythromycin (71%) and could be used safely as starter cultures. Those that presented resistance need to be genetically evaluated since the mechanism of resistance is probably related to mobile genetic elements carried by L plantarum
Physiological and biochemical responses to low non-freezing temperature of two Eucalyptus globulus clones differing in drought resistance
Abstract – We have compared the metabolic responses of leaves and roots of two Eucalyptus globulus L. clones CN5 and ST51 that differ in their
sensitivity to water deficits (ST51 is more drought sensitive), with regard to the effect of chilling (10/5 ◦C, day/night). We studied changes in growth,
osmotic potential and osmotically active compounds, soluble proteins, leaf pigments, and membrane lipid composition. Our data showed that both
clones have the ability to acclimatize to chilling temperatures. As a result of 10 days of acclimation, an increase of soluble sugars in leaves of treated
plants of both clones was observed that disappeared later on. Differences between clones were observed in the photosynthetic pigments and soluble
protein content which were more stable in CN5 under chilling. It also was apparent that CN5 presented a less negative predawn water potential (ψpd)
and a higher leaf turgor than ST51 throughout the chilling treatment. In the case of the CN5, increased total lipids (TFA) and concomitant increase
of linolenic acid (C18:3) in leaves after acclimatization may be related to a better clone performance under chilling temperatures. Moreover, a higher
constitutive investment in roots in the case of CN5 as compared to ST51 may benefit new root regeneration under low temperatures favoring growth
after cold Mediterranean winter
Acclimation to short-term low temperatures in two Eucalyptus globulus clones with contrasting drought resistance
We tested the hypothesis that Eucalyptus
globulus Labill. genotypes that are more resistant to dry
environments might also exhibit higher cold tolerances
than drought-sensitive plants. The effect of low temperatures
was evaluated in acclimated and unacclimated
ramets of a drought-resistant clone (CN5) and a
drought-sensitive clone (ST51) of E. globulus. We
studied the plants’ response via leaf gas exchanges, leaf
water and osmotic potentials, concentrations of soluble
sugars, several antioxidant enzymes and leaf electrolyte
leakage. Progressively lowering air temperatures (from
24/16 to 10/ 2 C, day/night) led to acclimation of both
clones. Acclimated ramets exhibited higher photosynthetic
rates, stomatal conductances and lower membrane
relative injuries when compared to unacclimated ramets.
Moreover, low temperatures led to significant increases
of soluble sugars and antioxidant enzymes activity
(glutathione reductase, ascorbate peroxidase and superoxide
dismutases) of both clones in comparison to plants
grown at control temperature (24/16 C). On the other
hand, none of the clones, either acclimated or not,
exhibited signs of photoinhibition under low temperatures
and moderate light. The main differences in the
responses to low temperatures between the two clones
resulted mainly from differences in carbon metabolism,
including a higher accumulation of soluble sugars in the
drought-resistant clone CN5 as well as a higher capacity
for osmotic regulation, as compared to the droughtsensitive
clone ST51. Although membrane injury data
suggested that both clones had the same inherent
freezing tolerance before and after cold acclimation,
the results also support the hypothesis that the droughtresistant
clone had a greater cold tolerance at intermediate
levels of acclimation than the drought-sensitive
clone. A higher capacity to acclimate in a short period
can allow a clone to maintain an undamaged leaf surface
area along sudden frost events, increasing growt
Together for cultural heritage: Booklet of recommendations for social partners
Archaeological Heritage Managemen
Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients
The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period). Tissue samples were used for mRNA expression analysis of drug-metabolizing enzymes. In patients, a cross-over study was performed. During three 24-h periods, after tamoxifen dosing at 8 a.m., 1 p.m., and 8 p.m., for at least 4 weeks, blood samples were collected for pharmacokinetic measurements. Differences in tamoxifen pharmacokinetics between administration times were assessed. The mRNA expression of drug-metabolizing enzymes showed circadian variation in mouse tissues. Tamoxifen exposure seemed to be highest after administration at midnight. In humans, marginal differences were observed in pharmacokinetic parameters between morning and evening administration. Tamoxifen Cmax and area under the curve (AUC)0–8 h were 20 % higher (P max was shorter (2.1 vs. 8.1 h; P = 0.001), indicating variation in absorption. Systemic exposure (AUC0–24 h) to endoxifen was 15 % higher (P < 0.001) following morning administration. The results suggest that dosing time is of marginal influence on tamoxifen pharmacokinetics. Our study was not designed to detect potential changes in clinical outcome or toxicity, based on a difference in the time of administration. Circadian rhythm may be one of the many determinants of the interpatient and intrapatient pharmacokinetic variability of tamoxifen
Relationship Between Sunitinib Pharmacokinetics and Administration Time: Preclinical and Clinical Evidence
Background and Objective: Circadian rhythms may influence the pharmacokinetics of drugs. This study aimed to elucidate whether the pharmacokinetics of the orally administered drug sunitinib are subject to circadian variation. Methods: We performed studies in male FVB-mice aged 8–12 weeks, treated with single-dose sunitinib at six dosing times. Plasma and tissue samples were obtained for pharmacokinetic analysis and to monitor messenger RNA (mRNA) expression of metabolizing enzymes and drug transporters. A prospective randomized crossover study was performed in which patients took sunitinib once daily at 8 a.m., 1 p.m., and 6 p.m at three subsequent courses. Patients were blindly randomized into two groups, which determined the sequence of the sunitinib dosing time. The primary endpoint in both studies was the difference in plasma area under the concentration–time curve (AUC) of sunitinib and its active metabolite SU12662 between dosing times. Results: Sunitinib and SU12662 plasma AUC in mice followed an ~12-h rhythm as a function of administration time (p ≤ 0.04). The combined AUC from time zero to 10 h (AUC10) was 14–27 % higher when sunitinib was administered at 4 a.m. and 4 p.m. than at 8 a.m. and 8 p.m. Twenty-four-hour rhythms were seen in the mRNA levels of drug transporters and metabolizing enzymes. In 12 patients, sunitinib trough concentrations (Ctrough) were higher when the drug was taken at 1 p.m. or 6 p.m. than when taken at 8 a.m. (Ctrough-1 p.m. 66.0 ng/mL; Ctrough-6 p.m. 58.9 ng/mL; Ctrough-8 a.m. 50.7 ng/mL; p = 0.006). The AUC was not significantly different between dosing times. Conclusions: Our results indicate that sunitinib pharmacokinetics follow an ~12-h rhythm in mice. In humans, morning dosing resulted in lower Ctrough values, probably resulting from differences in elimination. This can have implications fo
Salinity effects on photosynthetic pigments, proline, biomass and nitric oxide in Salvinia auriculata Aubl.
Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia
- …