Utjecaj glutaraldehida na svojstva želatinskih filmova

In this work gelatin film was prepared from cow\u27s bone. In order to increase mechanical stability of the prepared transparent film as well as decrease its swelling, glutaraldehyde (GTA) was used. Different mass fractions of GTA were utilized. It was observed that at w = 0.18 % of GTA the load at break of the film is δ= 53.7 N and the solubility decreased. The solubility of the film was measured as a dependant parameter of the swelling behavior. In this case it was decreased from 389 % to 156 % at 5 min for gelatin films without GTA and with 0.18 % GTA, respectively. FTIR spectroscopy results showed a peak for crosslinked gelatin at ΰ = 1650 cm-1. It means the crosslinking between gelatin and GTA has taken place. SEM micrographs confirm the porosity has decreased by increasing the GTA fraction, which is an indication of higher strength.U ovom je radu pripremljen želatinski film od kravlje kosti. Da bi se povećala mehanička stabilnost pripremljenog transparentnog filma kao i smanjilo njegovo bubrenje, upotrijebljen je glutaraldehid (GTA). Upotrijebljeni su različiti maseni udjeli mase GTA. Uočeno je da kod 0,18 % GTA prekidna sila filma iznosi 53,7 N i da se povećala topljivost. Topljivost filma izmjerena je kao parametar ovisan o ponašanju pri bubrenju. U ovom slučaju smanjio se s 389 % na 156 % kod 5 minuta za želatinske filmove bez GTA odn. s 0,18 % GTA. Rezultati spektroskopije FTIR pokazali su maksimum za umreženu želatinu kod 1650 cm-1. To znači da je došlo do umrežavanja između želatine i GTA. Mikroskopske slike SEM potvrđuju da se poroznost smanjila povećanjem dijela GTA, što je pokazatelj veće čvrstoće

Discovery of the inhibitory effect of a phosphatidylinositol derivative on P-glycoprotein by virtual screening followed by <i>in vitro</i> cellular studies

P-glycoprotein is capable of effluxing a broad range of cytosolic and membrane penetrating xenobiotic substrates, thus leading to multi-drug resistance and posing a threat for the therapeutic treatment of several diseases, including cancer and central nervous disorders. Herein, a virtual screening campaign followed by experimental validation in Caco-2, MDKCII, and MDKCII mdr1 transfected cell lines has been conducted for the identification of novel phospholipids with P-gp transportation inhibitory activity. Phosphatidylinositol-(1,2-dioctanoyl)-sodium salt (8∶0 PI) was found to significantly inhibit transmembrane P-gp transportation in vitro in a reproducible-, cell line-, and substrate-independent manner. Further tests are needed to determine whether this and other phosphatidylinositols could be co-administered with oral drugs to successfully increase their bioavailability. Moreover, as phosphatidylinositols and phosphoinositides are present in the human diet and are known to play an important role in signal transduction and cell motility, our finding could be of substantial interest for nutrition science as well

Updated standardized definitions for efficacy endpoints in adjuvant breast cancer clinical trials: STEEP Version 2.0

Purpose The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.Methods We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Results Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.Conclusion We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes

ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942.

The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug selection. ABC-transporter copy number, expression and activity were examined using real-time PCR, immunoblotting and flow cytometry. Drug responses were measured using growth assays. ABCB1 was upregulated in ICEC0942-resistant cells and there was cross-resistance to THZ1. THZ1-resistant cells upregulated ABCG2 but remained sensitive to ICEC0942. Drug resistance in both cell lines was reversible upon inhibition of ABC-transporters. CDK7i response was altered in adriamycin- and mitoxantrone-resistant cell lines demonstrating ABC-transporter upregulation. ABCB1 expression correlated with ICEC0942 and THZ1 response, and ABCG2 expression with THZ2 response, in a panel of cancer cell lines. We have identified ABCB1 upregulation as a common mechanism of resistance to ICEC0942 and THZ1, and confirmed that ABCG2 upregulation is a mechanism of resistance to THZ1. The identification of potential mechanisms of CDK7i resistance and differences in susceptibility of ICEC0942 and THZ1 to ABC-transporters, may help guide their future clinical use

The prevalence of hypertension among 7-12 year old schoolchildren in Kerman, Iran: A population-based study

Background: The aim of this study was to find the prevalence of chronic hypertension and prehypertension conditions among children. Methods: In this cross-sectional study, a total of 1017 students in Kerman schools were examined during a period from 2013 to 2014. The weight, height, body mass index (BMI), systolic and diastolic blood pressure and family history of high blood pressure were obtained. Pediatric Hypertension was defined as a mean systolic or diastolic reading (or both) � 95th percentile and prehypertension was defined as the blood pressure reading between the 90th and 95th percentiles of the predicted values based on gender, age and height. Results: According to the results, the prevalence of prehypertension and hypertension in schoolchildren was 1.9 and 3, respectively. According to BMI, 13.7 of children were overweight and 14.3 were obese. There was a positive association between BMI and the development of hypertension. Conclusion: Our findings demonstrated that approximately 3 of schoolchildren were afflicted with hypertension. Hypertension showed a positive association with overweight and obesity. © 2020, Kerman University of Medical Sciences. All rights reserved