In vitro oslobađanje hidrofilnih i hidrofobnih ljekovitih tvari iz liposomskih disperzija i gelova

A method for determining the rate of hydrophilic and hydrophobic drug entities release from different types of liposomal dispersions and gels using a dialysis method is described. Dibucaine base and 5-fluorouracil were used as model drugs for a hydrophobic and hydrophilic drug, respectively. A dialysis technique was employed. Release rates were affected by the rate of rotation of the paddles of the tablet dissolution tester, temperature, and volume of release medium. The method was used to evaluate the in vitro drug release from hydrophilic and hydrophobic drug entities from liposomal dispersions and gels. The in vitro release study of dibucaine base showed no burst effect, while the in vitro release study of 5-fluorouracil showed a clear burst effect with an initial fast release phase followed by a sustained release phase.Opisana je metoda za određivanje brzine oslobađanja hidrofilnih i hidrofobnih ljekovitih tvari iz različitih vrsta liposomskih disperzija i gelova koristeći dijalizu. Dibukain baza i 5-fluorouracil upotrebljeni su kao modeli hidrofobnog, odnosno hidrofilnog lijeka. Na brzinu oslobađanja utjecala je brzina rotacije lopatica u aparatu u koje je pokus izvođen, temperatura i volumem medija za oslobađanje. Metoda je upotrebljena in vitro praćenje oslobađanja ljekovite tvari iz liposomskih disperzija i gelova. In vitro oslobađanje dibukain baze ne pokazuje učinak naglog oslobađanja, a 5-fluorouracila pokazuje, s brzim inicijalnim oslobađanjem iza kojeg slijedi usporeno oslobađanje

In vitro oslobađanje hidrofilnih i hidrofobnih ljekovitih tvari iz liposomskih disperzija i gelova

A method for determining the rate of hydrophilic and hydrophobic drug entities release from different types of liposomal dispersions and gels using a dialysis method is described. Dibucaine base and 5-fluorouracil were used as model drugs for a hydrophobic and hydrophilic drug, respectively. A dialysis technique was employed. Release rates were affected by the rate of rotation of the paddles of the tablet dissolution tester, temperature, and volume of release medium. The method was used to evaluate the in vitro drug release from hydrophilic and hydrophobic drug entities from liposomal dispersions and gels. The in vitro release study of dibucaine base showed no burst effect, while the in vitro release study of 5-fluorouracil showed a clear burst effect with an initial fast release phase followed by a sustained release phase.Opisana je metoda za određivanje brzine oslobađanja hidrofilnih i hidrofobnih ljekovitih tvari iz različitih vrsta liposomskih disperzija i gelova koristeći dijalizu. Dibukain baza i 5-fluorouracil upotrebljeni su kao modeli hidrofobnog, odnosno hidrofilnog lijeka. Na brzinu oslobađanja utjecala je brzina rotacije lopatica u aparatu u koje je pokus izvođen, temperatura i volumem medija za oslobađanje. Metoda je upotrebljena in vitro praćenje oslobađanja ljekovite tvari iz liposomskih disperzija i gelova. In vitro oslobađanje dibukain baze ne pokazuje učinak naglog oslobađanja, a 5-fluorouracila pokazuje, s brzim inicijalnim oslobađanjem iza kojeg slijedi usporeno oslobađanje

Inhibition of VEGF and Angiopoietin-2 to Reduce Brain Metastases of Breast Cancer Burden

For metastases in the central nervous system, angiogenesis enhances metastatic potential and promotes progression. Primary factors which drive vessel growth are vascular endothelial growth factor (VEGF) and angiopoietin-2. Preclinical models show inhibition of either factor reduces metastases spread and inhibits growth. This work sets out to answer two questions in a preclinical mouse model. First, whether the combined inhibition of VEGF and angiopoietin-2, reduces passive permeability and limits drug uptake into brain metastases; and second, whether this inhibition reduces metastases burden in brain. We observed combinatorial inhibition of VEGF and angiopoietin-2, decreased (p \u3c 0.05) angiogenesis and vascular branching in an aortic ring assay and decreased (p \u3c 0.05) endothelial wound closure times. Using a brain metastases of breast cancer model (induced by intracardiac injections of brain seeking MDA-MB-231Br cells or 4T1Br cells), we observed, similar to VEGF, angiopoetin-2 expression correlates to increased angiogenesis (p \u3c 0.05) and increased lesion permeability. To determine efficacy, animals were administered bevacizumab plus L1-10 (angiopoietin inhibitor) twice per week until neurological symptoms developed. Lesion permeability significantly decreased by ∼50% (p \u3c 0.05) compared to untreated lesions, but remained ∼25% greater (p \u3c 0.0%) than brain. In subsequent experiments, animals were administered similar regimens but sacrificed on day 32. The number of metastatic lesions developed was significantly (p \u3c 0.001) reduced in the bevacizumab group (56%) and combination group (86%). Lesions’ size was reduced in bevacizumab treated lesions (∼67%) and bevacizumab and L1-10 treated lesions (∼78%) developing area \u3c 0.5 mm2. In summary, combinatorial inhibition of VEGF and angiopoietin reduces lesion permeability and brain metastatic burden

Early Childhood Mathematics Curriculum in the light of the standards of the National Council of Mathematics Teachers

This study aims at exploring the preschool mathematics curriculum in light of the National Council of Teachers of Mathematics Standards. The study researched a sample of (140) preschool educators. An analysis of the mathematical content of preschool Self-Learning curriculum was conducted, and Saudi preschool educators were surveyed, in terms of their educational practices, and the processes used in teaching mathematics in their classes In accordance with the U.S. national standards for mathematicians, it means the methods in which children interact with sports content or content, namely (problem solving- communication- logical thinking - representation - Connection), where the study showed that the reality of the components of the mathematics curriculum applied in kindergartens within Saudi Arabia achieved these standards at these levels was The application of representation, communication and connectivity are the most achieved in the self-learning curriculum units with ratios of (86.4%, 83%, 82%), respectively, while problem-solving and logical thinking have reached the minimum use in the classroom, indicating that these processes are the least interested in application from the sample point of view, with 80%, respectively, using them (80%, 67.80%), despite the critical importance of these two processes specifically in building mathematical concepts as they focus on the ability of the child to be focused on the ability of the child. To use his accumulated sports skills to meet challenges such as predicting and examining hypotheses in order to find a scientific solution to the sports situation

Early Childhood Teachers Beliefs about Mathematics Teaching and Learning

The current research aimed to investigate the beliefs that early childhood teachers adopt about teaching and learning mathematics in the kindergartens of the Kingdom of Saudi Arabia. The teachers are role models for the child from whom he draws his knowledge, behavior, attitudes, concepts and experiences. and their classroom practice, which positively affects the level of the child and his attitudes towards the learning and teaching processes in general, and the mathematics course in particular, because of its importance in real life because it helps him to think, make decisions and solve problems he faces in his life. This has been confirmed by many researches and studies that the child is affected by his teachers beliefs, behaviors, decisions and dealings with him and the extent to which these beliefs are positive, which are the result of his personal and professional experience. One of the early childhood teachers, and the results of the study revealed that the responses of early childhood teachers about their beliefs about the processes of learning and teaching mathematics in general were positive, where most of the beliefs came to a large degree. This indicates that the teachers of this stage have positive opinions and ideas about the learning and teaching processes and the educational system, which affects their teaching efficiency, which is reflected in the child’s level of mathematics in an effective and positive manner. That is why the researchers recommend the necessity of providing workshops to develop, develop and support positive beliefs. The teachers of this stage are in line with modern educational trends

The Effectiveness of a Program Based on Montessori Activities in Developing Practical Life Skills for Pre-school Children

The study aimed to measure the impact of a program based on Montessori activities in developing practical life skills for pre-school children.The study sample consisted of (80) children enrolled in kindergarten, divided equally into two groups: experimental and control in the age group (5-6) years, and the study followed the quasi-experimental approach and the following tools: the practical life skills scale, and the training program Based on Montessori activities prepared by the study team, and the results of the study concluded: There are statistically significant differences at the level of significance (0.01) between the mean scores of the children of the experimental and control groups in the post-measurement of life skills, and their totality is in favor of the children of the experimental group. The results also showed that there were statistically significant differences at the level of significance (0.01) between the mean scores of the children of the experimental group in the two measurements of practical life skills, and their total sum in favor of the post measurement, in addition to that there were no statistically significant differences between the mean scores of the children of the experimental group in the two post measurements. The traceability of practical life skills, and their totality. Finally, the results showed that there are no statistically significant differences at the level of significance (0.05) between the mean scores of the children of the experimental group in the dimensional measurement of my skills: (personal care, dealing with others) according to the gender variable (male / female), while significant differences were found. A statistic at the level of significance (0.05) between the mean scores of the children of the experimental group in the dimensional measurement of sensory focus and accuracy skill, and the total sum of practical life skills according to the gender variable (male / female) in favor of females

NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

Background: Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Methods: Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). Results: NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (\u3e20 ng/g for 168 h) versus conventional irinotecan (\u3e1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Conclusions: Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results

Infinitesimal Idealization, Easy Road Nominalism, and Fractional Quantum Statistics

It has been recently debated whether there exists a so-called “easy road” to nominalism. In this essay, I attempt to fill a lacuna in the debate by making a connection with the literature on infinite and infinitesimal idealization in science through an example from mathematical physics that has been largely ignored by philosophers. Specifically, by appealing to John Norton’s distinction between idealization and approximation, I argue that the phenomena of fractional quantum statistics bears negatively on Mary Leng’s proposed path to easy road nominalism, thereby partially defending Mark Colyvan’s claim that there is no easy road to nominalism