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1.
Gera D Eytan 《Biomedicine & Pharmacotherapy》2005,59(3):90-97
Passive uptake of drugs into cells is described in terms of the following steps: (1) massive immediate binding of the drugs to the outer leaflet of the plasma membrane resulting in practical equilibrium between extremely high drug concentrations at the cell surface compared to the drug concentration in the medium. (2) Due to their amphipathic nature, anticancer drugs are practically excluded from the lipid core of the membrane. They cross the lipid core by distinct flip-flop events that occur in the case of doxorubicin and daunorubicin after an average period of 0.7 and 0.15 min, respectively. (3) The drug reaching the inner leaflet of the plasma membrane is in practical equilibrium with the drug present in the cytoplasm. (4) Almost all the amounts of anticancer drugs present in the cells are bound by molecular sinks, such as DNA or cytoskeleton elements. The resistance afforded to multidrug resistant (MDR) cells by extrusion pumps, such as P-glycoprotein, is negatively correlated with the affinity of the drugs to the membranes and with their flip-flop rates across membranes. Binding rates of the drugs to membranes and intracellular sinks have no effect on drug concentration in the cytoplasm once equilibrium is reached between the passive uptake of drugs and their active extrusion. 相似文献
2.
Fidder HH Olschwang S Avidan B Zouali H Lang A Bardan E Picard O Bar-Meir S Colombel JF Chowers Y 《American journal of medical genetics. Part A》2003,(3):240-244
Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non-Ashkenazi Jewish patients were observed. Age-of-onset of disease was lower in Ashkenazi mutation carriers as compared to non-carriers of Ashkenazi origin (18.7 +/- 8.6 years vs. 25.8 +/- 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non-carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age-of-onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior. 相似文献
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Embryo transfer (ET) is the last stage of extracorporal fertilization during which the embryo is placed in the uterine cavity with a medium-filled catheter 2–3 days after in vitro fertilization. While fertilization in the laboratory occurs at very high rates (>:90%), the overall success of the procedure (i.e., take home baby) is still very low (<25%) and assumed to be mainly due to implantation failure. A computational model was developed to simulate ET within the uterine cavity by a fluid-filled catheter inserted into a two-dimensional channel with oscillating walls. The results showed that the speed at which the embryos are injected from the catheter dominates the procedure and controls the velocity of their transport within the uterine cavity. ET at excessively high injection speeds may lead to ectopic pregnancies, while uterine peristalsis affects transverse dispersion only during injection at low injection speeds. The presence of the catheter within the uterus does not affect flow patterns downstream of its tip. The potential risks to implantation failure due to mechanical factors involved in the ET processes are discussed. © 2003 Biomedical Engineering Society.
PAC2003: 8719-j, 8710+e 相似文献
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Hallie B. Hinen MD Robert M. Gathings MD Marshall Shuler MD Lara Wine Lee MD PhD 《Pediatric dermatology》2018,35(1):e88-e89
We report the successful treatment of multiple facial milia with manual extraction and tretinoin in a child with orofaciodigital syndrome type 1. Treatment with topical medications may be insufficient in individuals with orofaciodigital syndrome type 1, and pitted scarring is often a sequala. This case demonstrates that manual extraction is well tolerated and effective in the treatment of multiple milia. In addition, clinicians need to be aware of this rare genetic condition, which commonly presents de novo and can lead to significant morbidity if untreated. 相似文献
8.
Eytan M. Debbi Benjamin Bernfeld Amir Herman Moshe Salai Yocheved Laufer Alon Wolf 《The Journal of arthroplasty》2019,34(1):47-55
Background
Biomechanics after total knee arthroplasty (TKA) often remain abnormal and may lead to prolonged postoperative recovery. The purpose of this study is to assess a biomechanical therapy after TKA.Methods
This is a randomized controlled trial of 50 patients after unilateral TKA. One group underwent a biomechanical therapy in which participants followed a walking protocol while wearing a foot-worn biomechanical device that modifies knee biomechanics and the control group followed a similar walking protocol while wearing a foot-worn sham device. All patients had standard physical therapy postoperatively as well. Patients were evaluated throughout the first postoperative year with clinical measures and gait analysis.Results
Improved outcomes were seen in the biomechanical therapy group compared to the control group in pain scores (88% vs 38%, P = .011), function (86% vs 21%, P = .001), knee scores (83% vs 38%, P = .001), and walking distance (109% vs 47%, P = .001) at 1 year. The therapy group showed healthier biomechanical gait patterns in both the sagittal and coronal planes at 1 year.Conclusion
A postoperative biomechanical therapy improves outcomes following TKA and should be considered as an additional therapy postoperatively. 相似文献9.
Chelsea Eason MSCR Ahmad Aleisa MD Julie R. Jones PhD Eloise J. Prijoles MD Lara Wine Lee MD PhD 《Pediatric dermatology》2020,37(5):915-917
FILS syndrome (facial dysmorphism, immunodeficiency, livedo, and short stature) is a rare autosomal recessive disorder caused by pathogenic alterations in the POLE gene leading to multisystemic manifestations, including poorly characterized skin findings. We report a child with a homozygous variant, c.100C > T (p.Arg34Cys), in POLE and features consistent with poikiloderma, expanding the dermatologic signs associated with this rare disorder. Additionally, we review reported cases of FILS syndrome, discuss possible pathomechanisms for our patient's presentation, and consider implications for management. 相似文献
10.
Fish consumption is of great importance to children’s health and is essential for neurodevelopment, which begins in pregnancy and continues throughout early childhood and into adolescence. However, fish consumption presents conflicting health outcomes associated with its nutritional benefits and its adverse contaminant risks, because both avoiding fish as well as the consumption of contaminated fish can potentially harm children. This may be challenging to communicate. The present review was performed to assess the current knowledge and recommendations around ‘smart’ fish-consumption decisions. Health Canada advises, as well as other advisories and guides, that fish should be consumed for its health benefits, while also informing consumers, especially women and children, to limit certain fish consumption. The current literature must attempt to handle the challenges inherent in communicating the dilemmas of children’s fish consumption. Incorporation of new knowledge translation strategies are proposed as a means to raise the level of knowledge about optimal fish consumption practices. 相似文献