Stealth (pegylated) liposomal doxorubicin (Doxil) has been extensively studied at the pre-clinical and clinical level in recent years. However, one issue not yet addressed is the effect of dose on tumor localization and therapeutic efficacy of Doxil. Although it has been reported that the pharmacokinetics of drug-free Stealth liposomes is independent of dose within a certain range, clinical pharmacokinetic analysis of Doxil suggests a dose-dependent clearance saturation phenomenon when a broad dose range is examined. In addition, liposome-encapsulated doxorubicin can exert toxic effects on the liver macrophage population in the form of impairment of the phagocytic function and reduced ability of colloid particle clearance. In studies with tumor-bearing mice in which the dose of Doxil was escalated from 2.5 to 20 mg/kg, we demonstrate that dose escalation results in a saturation of Doxil clearance and a disproportional increase of the amount of liposomal drug accumulating in tumor. Experiments with radiolabeled highly negatively-charged liposomes injected into mice previously treated with Doxil are consistent with a partial blockade of the reticulo-endothelial system with relative reduction of liver uptake and greater prolongation of liposome circulation time. The clearance saturation effect is seen after Doxil in a dose-dependent fashion, and not after a similar free doxorubicin dose or similar phospholipid dose in drug-free liposomes. A trend to superior therapeutic efficacy for treatments based on larger doses as compared to smaller split doses, while maintaining an equivalent dose intensity, was also observed. These observations may be relevant to the choice of dose-schedule of Doxil to ensure optimal anti-tumor activity. Therefore, dose-dependent liposomal doxorubicin blockade of the reticulo-endothelial system may prolong liposome circulation time and enhance significantly drug delivery to tumors.
A case of proximal femoral deficiency in a fetus, associated with ventriculomegaly and oligohydramnios is described. Vaginal ultrasonographic diagnosis was made in the 14th week of gestation in a 37-year-old asthmatic woman. Ultrasonic follow-up until termination of pregnancy in the 20th week of gestation was performed. The importance of early diagnosis and the possible roles of oligohydramnios and antiasthmatic medications are discussed.
Bacterial quorum sensing (QS) is a form of cell-to-cell communication which is vital to the pathogenicity of many bacteria, and therefore a promising target for the development of new treatments for microbial infections. While many medicinal plants possess antibacterial activity, only a few plants have been shown to target quorum sensing. In the face of increased microbial resistance to existing antibiotics coupled with the decline in novel antibiotic development, QS inhibitors from medicinal plants is a promising direction for new antibacterial treatments,. The purpose of this review is to summarize the verified data on the anti-QS properties of medicinal plants and the various mechanisms of their actions.
Electronic poster abstracts stored ultrasound images were blinded evaluated by an expert operator and results were compared. Results: 254 women were performed. 265 fetuses were examined (10 twin pregnancies). Average wg was 12,4 ± 0,4. Visualization of CRL, NT, NB , CC, AC, Upper and Lower Bones, falx cerebri, thalamus, lens, jaw, bone palate, stomach, lungs, upper and lower limb bones, bladder, umbilical arteries, cardiac four chambers (4Cw) and great vessels sections (3Vw) was above 98%( confirmed by expert operators). Discordant % of visualization was found for iNT (95 vs 90), Cerebellum (88%vs72%) brain stem (97%vs88%) Lens (100%vs95%) Diaphragm (99%vs92%) Thymus (14%vs11%). Kidneys (99%vs95%) renal arteries (92%vs55%) TR (96%vs90%) aortic arch (96%vs79%) DV (97%vs88%). Complete concordance between normal and abnormal evaluation was assessed. Conclusions: Ultrasound screening for fetal malformations at 11-13 + 6 wg is feasible even if performed after a brief training. Pitfalls in the visualization of kidneys, ductus venosus flow ant tricuspid regurgitation are frequent. The proportion of these two components slightly increases with CRL. However, this model supposes a constant CRL-independent variability in both distributions. As in fetal biometry most biometrical parameters show an increasing variability with gestational age, the aim of this study was to establish a mixture model using different method allowing the change of variability. Methods: This was retrospective study of singleton pregnancies (CRL 45-81 mm) which underwent routine first-trimester screening in Centre of Fetal Medicine Gennet in Prague from January 2005 till March 2014. The pregnancies with any chromosomal anomaly were excluded. Our assumption was that NT measurements on logarithmic scale follow a mixture of two normal distributions, N(μ, σ2) and N(τ, ν2), with p and (1-p) probabilities that each value comes from first and second distributions, respectively. Our dataset was divided into 9 groups with 4mm CRL increments. For each group the parameters p, μ, σ, τ and ν were estimated with 95% CI using maximum likelihood estimation. The obtained model was compared to WMM. Results: There were 28716 NT measurements eligible for the study. The proportion of CRL-dependent NT was slightly higher than in WMM and increased with CRL from 0.93 to 0.98. Regarding CRL-dependent NT distribution, median NT increased with CRL significantly lower compared to WMM. Looking at CRL-independent NT distribution, median NT slightly increased up to CRL of 67mm, then dropped backwards to the level exactly same as in WMM. The variabilities in both distributions did not show any distinct trend and was similar to WMM. Conclusions: Our established mixture model of NT distribution showed overall concordance with previously published model. The main differences were slightly higher proportion of CRL-dependent component and more gradual increase of NT median in CRL-dependent NT. The variability in both distributions did not show any clear trend with CRL. Objectives: Rece...
Objective: To compare the yield of multiple-marker biochemical screening with that of minor fetal anomalies observed on ultrasound for detection of aneuploidy in low-risk patients. Methods: The results of 1,073 amniocenteses performed because of abnormal biochemical screening tests were compared against 197 amniocenteses performed for minor anomalies as detected on level II ultrasound at 15–22 weeks of gestation. Results: False-positive results were observed in about 7% of serum screening patients and in 1.7% of the ultrasound cases. Chromosomally abnormal fetuses were detected in 2% of the amniocenteses performed because of abnormal serum screening and in 2.5% of the cases with ultrasound-defined minor anomalies. Conclusions: Both methods identify patients at risk for abnormal karyotypes. Although the evaluation of serum biochemical markers yielded more false-positive results, it is more suitable than ultrasound for mass population screening.
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