Ethacridine Research Articles

Synthesis, antibacterial and antiproliferative potential of some new 1-pyridinecarbonyl-4-substituted thiosemicarbazide derivatives

In this study, the antibacterial, cytotoxic and antiproliferative activities of novel thiosemicarbazide derivatives were assessed. Our results demonstrated that some of the novel compounds possess good antibacterial properties against Staphylococcus epidermidis, Streptococcus mutans and Streptococcussanguinis and are only slightly cytotoxic; thus, they exhibit an excellent therapeutic index, which is higher than that of ethacridine lactate. Moreover, our data showed that compounds 2 and 4 have an antiproliferative activity against human breast adenocarcinoma and human hepatocellular carcinoma cell lines. We expect that the novel thiosemicarbazide derivatives can be used as agents for treatment of dental caries and also for chemotherapy support.Electronic supplementary materialThe online version of this article (doi:10.1007/s00044-016-1599-6) contains supplementary material, which is available to authorized users.

Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.

Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

Risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa

To investigate the risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa. Clinical data of 24 pregnant women of second and third trimester with a scarred uterus and placenta previa,who requested termination in Women's Hospital Zhejiang University School of Medicine from July 2009 to June 2014, were retrospectively analyzed. The method of mifepristone combined with ethacridine lactate was adopted for all cases. Mifepristone combined with ethacridine lactate and uterine artery embolization were routinely given for patients with complete placenta previa. Cesarean section was performed for patients who failed to delivery or underwent massive vaginal bleeding before delivery. Age, gestational weeks, gravidity and parity, times of previous cesarean section, the interval from previous operation, the position and the type of placenta previa, placenta accretet, the indication and method of termination, postpartum hemorrhage, successful rate of labor induction, placental retention ratio and uterus rupture were documented. The successful rate of labor induction was 83.3%. The analysis showed that age, gestational weeks, gravidity and parity and times of previous cesarean section were not risk factors for failed labor induction, however the interval time from previous operation was related to induction failure (P<0.05). Patients with previous cesarean section ≥ 13 years were more likely to require cesarean section than those <13 years (P<0.05). The placenta adhered to the antetheca of the uterus or placenta accrete increased risk to have cesarean section. There were no significant differences in postpartum hemorrhage, the successful rate of labor induction, placental retention ratio and the rate of uterine rupture between patients with uterine artery embolization and those without. The labor induction would be feasible for women with a scarred uterus and placenta previa in second and third-trimester pregnancy. The previous operation ≥ 13 years, the antetheca placenta or placenta accrete might increase the incidence of labor induction, while the uterine artery embolization would rise the successful rate of labor induction.

The combination of Kangfuxing liquid, ethacridine lactate and local oxygen therapy in the treatment of radiation-induced skin damage

Objective To investigate the efficiency of Kangfuxing liquid, ethacridine lactate in combination with local oxygen therapy for radiation-induced skin damage. Methods A total of 96 patients affected by radiation-induced skin damage were enrolled and randomly allocated to a treatment group and a control group by random number table method, with 48 patients in each group. All patients in the control group were treated with trolamine cream, and those in the treatment group were treated with Kangfuxing liquid, ethacridine lactate in combination with local oxygen therapy. Skin dermatitis was scored utilizing Radiation Therapy Oncology Group (RTOG) toxicity scale. Results The total effective rate in the treatment group was significantly higher than that in the control group (97.9% vs. 79.1%; χ2=10.119, P=0.002). The distribution of patients with RTOG grades 0 to 4 showed different degrees of improvement, and the number of patients with RTOG 0-4 grades changed from 0, 3, 9, 12, 24 before the treatment to 8, 12, 22, 6, 0 after the treatment in the treatment group, 0, 2, 10, 25, 11 to 2, 5, 18, 23, 0 in the control group. The percent of patients with RTOG grade 0 in the treatment group was significantly increased than that in the control group (16.7% vs. 4.2%; χ2=4.019, P=0.045) and the percent of patients with RTOG grade 3 significantly decreased (12.5% vs. 47.9%; χ2=12.649, P<0.001). The percents of patients with dispirited spirit (31.3% vs. 58.3%; χ2=6.066, P=0.014), dry and chapped skin (20.8% vs. 58.3%; χ2=12.588, P=0.000) in the treatment group were all significantly lower than those in the control group. Conclusion Kangfuxing Liquid, ethacridine lactate in combination with local oxygen therapy can improve radiation-induced skin damage. Key words: Radiodermatitis; Ethacridine; Oxygen; Kangfuxing liquid

Clinical analyses of 66 cases of mid-trimester pregnancy termination in women with prior cesarean.

Background:The rate of cesarean delivery has significantly increased in China in the last decade. Women with prior cesarean history tend to have a higher risk of uterine rupture during termination of the pregnancy in mid-trimester than those without such a history. The aim of our study was to evaluate the influences of the potential risk factors on uterine rupture in women with prior cesarean.Methods:We conducted this retrospective study of women with prior cesarean section, who underwent mid-trimester pregnancy termination between January 2006 and December 2013 in Peking Union Medical College Hospital. The protocol was oral administration of mifepristone and misoprostol for the patients with the gestational ages below 16 weeks or intra-amniotic injection of ethacridine lactate (EL) for those with at least 16 weeks of gestational ages. The thickness of the lower uterine segment (LUS) was measured before the termination of pregnancy. Logistic regression was used to study the risk factors of uterine rupture.Results:The total rate of successful abortion was 93.9% (62/66). Four patients failed in induction, and one of them received curettage, whereas the other three experienced uterine rupture (4.5%). The successful rates of abortion were 85.7% (30/35) for women treated with mifepristone-misoprostol and 86.1% (31/36) for those treated with EL. There was a significant difference in the mean LUS thickness between the uterine rupture group (3.0 ± 2.0 mm) and the nonrupture group (7.0 ± 3.0 mm) (P < 0.05). The LUS thickness of <3 mm was associated with uterine rupture during mid-trimester pregnancy termination in women with prior cesarean (odds ratio, 94.0; 95% confidence interval 4.2–2106.1) after adjusted maternal age, gestational age, interdelivery interval and prior cesarean section. Severe bleeding that required transfusion occurred in one case (1.5%).Conclusions:Both the mifepristone-misoprostol and the EL regimens were effective and safe for the termination of mid-trimester pregnancy in women with prior cesarean. A thinner LUS is associated with a relatively high risk of uterine rupture.

Effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for termination of second trimester pregnancy in patients with liver dysfunction.

Severe liver dysfunction in pregnancy (SLDP) is rare but serious complications with high mortality rate. This study compared the effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy in patients with SLD. A total of 55 patients with indications of labor induction were enrolled and analyzed by retrospective control analysis method. Twenty-three cases adopted Cook double balloon dilation as Cook group, and 32 cases received intra-amniotic injection of ethacridine lactate as EL group. The primary outcome was evaluated by successful abortion rate and the difference in the induction-to-abortion interval. Secondary outcomes included liver function recovery and the frequency of adverse events. Both Cook and EL regimens were effective, with successful abortion rate of 87.0% and 93.8%, respectively (P=0.639). The induction-to-delivery interval was similar between Cook group and EL group (38.1 ± 21.5 vs. 41.3 ± 17.4, P=0.543). The liver disease status was more severe in Cook group than in EL group, but it did not show any significant difference after pregnancy termination between the two groups and the improvement rate also did not show any significant difference. Both treatments were safe and there was no significant difference in bleeding and cervical laceration adverse events between the two groups. Our study firstly compared double-balloon catheter and ethacridine lactate for the induction of labor in women with SLD during second trimester pregnancy.

Comparative Study of Efficacy of Extra-amniotic Ethacridine Lactate with Oxytocin Versus Extra-amniotic Ethacridine Lactate with Intravaginal Misoprostol for Termination of Pregnancy with IUD Anamolous Fetuses in Second and Third Trimesters

Termination of a pregnancy in second and third trimesters involving a dead foetus or one with a lethal anomaly is a challenge for health-care professionals in any setting. In addition to the theoretical concern of the dead foetus inutero causing disseminated intravascular coagulation, continuation of such a pregnancy may not be psychologically and socially acceptable to many women, and both the woman and the caretaker are keen to terminate the pregnancy, preferably without an incision on the uterus. Mid-trimester termination of pregnancy is one of the most controversial areas of gynaecological practice. It has moral, emotional, social and technical issues. There is continuous need for termination of pregnancy in second trimester, more recently due to increase in the use of antenatal diagnostic procedures. Nowadays, majority of mid-trimester abortions are carried out medically. The development of prostaglandin analogues has been a major breakthrough in abortion technology. Natural prostaglandins such as PGE1, PGF2a, PGE2, PG analogues like 15-methyl PGF2a have been used by various routes such as intravenous, intramuscular, intra/extra amniotic, oral and vaginal. Ethacridine lactate works by producing prostaglandin from deciduas, whereas misoprostol being synthetic analogue of misoprostol is supposed to act directly. This study aims to evaluate the effectiveness and safety of the extra-amniotic instillation of ethacridine with vaginal misoprostol in comparison to extra-amniotic instillation of ethacridine lactate with oxytocin IV infusion in terminations of second and third trimester pregnanciesin a tertiary referral hospital catering for both rural and urban population. This study concludes that ethacridine lactate with misoprostol is as efficacious as ethacridineplus oxytocinin termination of second and third trimesters anamolus/IUD foetuses. Though there is no significant difference in efficacy between the two. The ethacridineplus misoprostol is slightly effective in reducing the I-A interval. The efficacy of ethacridine plus misoprostol is slightly higher in early second trimester and ethacridine plus oxytocin is effective in the third trimester.

Ibrutinib Sensitizes AML Cells to ROS Inducers Via a BTK-Independent Mechanism

Ibrutinib is a small-molecule Bruton’s tyrosine kinase (BTK) inhibitor yielding impressive clinical responses in B-cell malignancies, where BTK contributes to disease development and progression. We noted that BTK is expressed and constitutively active in acute myeloid leukemia (AML) cell lines and in a subset of AML patients. We therefore sought to determine BTK’s potential role in AML. Using BTK-pY223 expression on immunoblot as a marker of BTK activity, we demonstrated that ibrutinib doses as low as 1μM were sufficient to inhibit BTK activity in the AML cells TEX and OCI-AML2. Yet, these cell lines were insensitive to ibrutinib compared to the B-cell lymphoma Daudi cell line (IC50 10.4μM and 23.7μM versus 1.1μM, respectively). Although inactive as a single agent, we sought to identify drug combinations that sensitized AML cells to pharmacologically relevant concentrations of ibrutinib by conducting a combination chemical screen with our in-house known drug library in TEX and OCI-AML2 cells. According to excess-over-Bliss additivism criteria, we determined that in both cell lines, the poly(ADP-ribose) glycohydrolase inhibitor ethacridine lactate was the most synergistically cytotoxic, producing an 8-fold reduction in the IC50 of ibrutinib. Synergistic cytotoxicity was also observed in a subset of primary AML cells, but not normal hematopoietic cells. Mechanistically, the combination’s synergistic cytotoxicity resulted from excessive ROS production (>10-fold increase, versus a <2-fold increase with either drug alone in TEX and OCI-AML2), since α-tocopherol addition to combination-treated cells rescued cell viability from 24% to 85% and from 4% to 84% in TEX and OCI-AML2, respectively. Combining ibrutinib with other ROS-inducing agents such as parthenolide and the first-line AML therapy daunorubicin produced similar synergistic effects in AML cells,with α-tocopherol also rescuing cell viability. However, the synergistic effects were likely not related to inhibition of BTK, as knockdown of BTK with shRNA did not sensitize TEX cells to ethacridine or daunorubicin and thus did not recapitulate the effects of ibrutinib. We therefore conclude that the BTK inhibitor ibrutinib lacks single agent anti-AML activity, but synergizes with ROS-inducing agents including daunorubicin by inhibiting targets beyond BTK. Thus, clinical trials of ibrutinib in combination with standard chemotherapy could be warranted in AML. DisclosuresNo relevant conflicts of interest to declare.

The study of the influence of a photosensitizer and combined effects of low-intensity laser radiation on the composition of the microflora of the dental plaque

The effect of low-intensity laser radiation (LILR) on the background of a photosensitizer (ethacridine lactate) on selective elimination of pathogenic and conditionally pathogenic microorganisms has been studied. Taking into account antiseptic properties of ethacridine lactate the maximally possible time of influence of ethacridine lactate as a photosensitizer should be set. It has been found that after the influence of rivanol (ethacridine lactate) within 1.5-3 minutes the bactericidal action on microorganisms is observed. The effect of antiseptic in the interval from 30 to 60 seconds was not accompanied with the expressed quantitative change of the microbial population. The second stage of the research was identification of microorganisms sensitivity to various concentrations of the photosensitizer. As a photosensitizer the aqueous solution of ethacridine lactate in the concentrations of 0.1; 0.05; 0.01% was used. The results obtained allow to conclude that the concentration of 0.1% solution of ethacridine lactate increases the sensitivity of microorganisms to the effects of low-intensity laser radiation. During the experiment the combined impact of the antimicrobial activity of 0.1% solution of ethacridine lactate and blue spectrum laser radiation has been determined; it is manifested by decrease in the number of CFU/ml of the total microflora of the dental plaque. The number of CFU is reduced from 14.3 ± 0.12 . 10 3 /ml up to 2.4 ± 0.3 . 10 2 /ml after exposure (Table 1). Comparing the data of the control (the initial number of the colonies grown) and the experiment (the number of the colonies grown after the photoactivated disinfection) we have found that the antibacterial action of photoactivated disinfection depends directly on duration of exposure. Thus, the effectiveness of combined use of a photosensitizer with LILR is 1.2 times higher than that of ethacridine lactate (the exposure time is 60 seconds), and 2.0 times higher than the antimicrobial effect of the laser blue spectrum (the exposure time is 120 seconds).

Effectiveness of mifepristone in combination with ethacridine lactate for second trimester pregnancy termination

ObjectiveTo compare the efficacy of mifepristone and ethacridine lactate with ethacridine lactate alone for second trimester pregnancy termination. Study designTwo hundred and seventy-six healthy women between 16 and 27 weeks of gestation, desiring a termination, were assigned at random into two groups. The study group consisted of 140 women who received an intra-amniotic injection of 100mg ethacridine lactate, followed by oral administration of 50mg mifepristone at 0, 12 and 24h (total dose of mifepristone 150mg). The control group consisted of 136 women who received an intra-amniotic injection of 100mg ethacridine lactate alone. The primary outcome measure was the induction-to-abortion interval. Secondary outcomes included blood loss in 24h, successful abortion rate, retained placental tissue rate, rate of uterine evacuation and cervical laceration. ResultsInduction-to-abortion interval, blood loss in 24h, rate of retained placental tissue and uterine evacuation were significantly less in the study group compared with the control group (p<0.001). Termination was successful in 140 of 140 women (100%) in the study group and 133 of 136 women (97.8%) in the control group. All women in the study group delivered within 72h, and three nulliparous women in the control group did not deliver within 72h. The cervical laceration rate was 0 and 1.47% (2/136) in the study group and the control group, respectively. No significant difference in the successful abortion rate (p=0.235) or the cervical laceration rate (p=0.242) was found between the two groups. ConclusionMifepristone in combination with ethacridine lactate may significantly improve the outcomes of second trimester pregnancy termination compared with ethacridine lactate alone, without increasing complications and side effects apart from nausea.

Small-molecule screening of PC3 prostate cancer cells identifies tilorone dihydrochloride to selectively inhibit cell growth based on cyclin-dependent kinase 5 expression.

Cyclin-dependent kinase 5 (CDK5) is a potential target for prostate cancer treatment, the enzyme being essential for prostate tumor growth and formation of metastases. In the present study, we identified agents that target prostate cancer cells based on CDK5 expression. CDK5 activity was suppressed by transfection of PC3 prostate cancer cells with a dominant-negative construct (PC3 CDK5dn). PC3 CDK5dn and PC3 control cells were screened for compounds that selectively target cells based on CDK5 expression, utilizing the Johns Hopkins Drug Library. MTS proliferation, clonogenic and 3D growth assays were performed to validate the selected hits. Screening of 3,360 compounds identified rutilantin, ethacridine lactate and cetalkonium chloride as compounds that selectively target PC3 control cells and a tilorone analog as a selective inhibitor of PC3 CDK5dn cells. A PubMed literature study indicated that tilorone may have clinical use in patients. Validation experiments confirmed that tilorone treatment resulted in decreased PC3 cell growth and invasion; PC3 cells with inactive CDK5 were inhibited more effectively. Future studies are needed to unravel the mechanism of action of tilorone in CDK5 deficient prostate cancer cells and to test combination therapies with tilorone and a CDK5 inhibitor for its potential use in clinical practice.

Antibiotics and antiseptics for venous leg ulcers.

Antibiotics and antiseptics for venous leg ulcers.

A Comparative study of Extra-Amniotic Instillation of Ethacridine with Tablet Dinoprostone (PGE2) in Second Trimester Abortion Versus Ethacridine Alone

Aims: To study the efficacy of combination of extra-amniotic instillation of ethacridine with tablets Dinoprostone (PGE2) in second trimester abortion as compared to ethacridine alone. Methods: One hundred patients undergoing second trimester abortion were divided into two groups. Fifty patients received extra-amniotic ethacridine lactate 150 ml through Foley’s catheter (Ethacridine group) and the other 50 patients received 150 ml extra-amniotic ethacridine lactate mixed with a 0.5 mg of a crushed tablet of Dinoprostone through Foley’s catheter (Combination group). Both the groups were compared in respect to instillation-abortion interval, completeness of abortion and success rate. Results: The mean age, multiparity parity, and gestational age were comparable in both the groups. The instillation- abortion interval was significantly shorter in combination group as compared to ethacridine group (16.4±7.1 vs. 29.9 ±13.9 hours, p&lt;0.001). Two patients in combination group had instillation abortion interval more than 48 hours as compared to 16 patients in ethacridine group(p&lt;0.0005). Forty one patients (82%) in combination group had complete abortion as compared to 37 (74%) patients in ethacridine group. The success rate was 48/50(96%) in combination group as compared to 45/50 (90%) in ethacridine group. Conclusions: Addition of a 0.5 mg of crushed tablet of Dinoprostone in extra-amniotically instilled ethacridine lactate reduced the instillation-abortion interval significantly, increased the chances of complete abortion and increased the success rate. Nepal Journal of Obstetrics and Gynaecology / Vol 7 / No. 1 / Issue 13 / Jan- June, 2012 / 25-27 DOI: http://dx.doi.org/10.3126/njog.v7i1.8831

Comparison of efficacy and safety of mifepristone- misoprostol combination with ethacridine lactate in mid-trimester termination of pregnancy

This study was done to compare the effectiveness and safety of mifepristone/misoprostol versus extra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy. Sixty women requesting voluntary termination of pregnancies, between 13 and 20 weeks of gestation, were randomly assigned into two groups. Group 1 (MM) received a single oral dose of 200 mg mifepristone and 48 h later 400 mcg vaginal misoprostol every 4 h, with up to five additional doses. Group 2 (EL) received an extra-amniotic injection of 150 ml of ethacridine lactate with 250 mcg of PGF2α. The primary outcome was successful abortion rate. Secondary outcomes included the difference in the induction-to-abortion interval and the frequency of adverse events. Both MM and EL regimens were effective, with successful abortion rates of 96.67 and 93.33%, respectively (P value > 0.05, NS). The complete abortion rates were 90 and 86.66%, respectively. The induction-to-abortion interval was longer in the MM group than in the EL group that is, (58.31 ± 3.62 h) versus (32.28 ± 9.94 h), respectively, P < 0.001, VHS). Both treatments were safe, although there was a significant difference in duration of hospital stay between the two groups. Both MM and EL regimens were effective with high success rates and were safe for the termination of second trimester pregnancy. Key words: Mifepristone, misoprostol, pregnancies, abortion, treatments.

THU0346 Dnase Activity of Polyclonal IgGs – A Putative Serological Marker in Patients with Spondyloarthritides

BackgroundAntibodies executing catalytic activity are referred to as antibody enzymes or short “abzymes” and may have diagnostic relevance. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune...

Efficacy of antiseptics containing povidone‐iodine, octenidine dihydrochloride and ethacridine lactate against biofilm formed by Pseudomonas aeruginosa and Staphylococcus aureus measured with the novel biofilm‐oriented antiseptics test

Increasing data suggesting that microorganisms in the biofilm form are among the leading agents of persistent infections of chronic wounds require the development of new approaches to treatment. The aim of this article was to compare the efficacy of three commonly used antiseptics using a biofilm-oriented approach. Biofilm-oriented antiseptics test (BOAT), the innovative method, allows to estimate, in a quick and reliable manner, the in vitro activity of working solutions of antiseptics in real contact times against bacteria in the biofilm form and to use the results in the selection of an appropriate antiseptic to treat local infections in the clinical practice.

Matrix-Assisted Laser Desorption/Ionization Matrices for Negative Mode Metabolomics

Matrix-assisted laser desorption/ionization (MALDI) has been shown to be highly sensitive for analyzing low-mass compounds such as metabolites if the right matrix is used. 9-aminoacridine (9AA) is the most commonly employed matrix for negative mode MALDI-MS in metabolomics. However, matrix interferences and the strongly varying sensitivity for different metabolites make a search for alternative matrices desirable, in order to identify compounds with a different chemical background and/or favoring a different range of analytes. We tested the performance of a series of potential negative mode MALDI matrices with a mix of 29 metabolites containing amino acids, nucleotide phosphates and Krebs cycle intermediates. While ethacridine lactate was found to provide limits of detection (LODs) in the low femtomole range for nucleotide phosphates, amino acids and Krebs cycle intermediates in the low picomole range, 4-amino-2-methylquinoline showed LODs in the picomole range for most metabolites, but is capable of ionizing a broader range of analytes than both 9AA and ethacridine.

The nursing observation of treatment of pediatric irritant dermatitis using ethacridine lactate and double hose wind scattered

Objective To investigate the clinical efficacy of treatment of pediatric irritant dermatitis using ethacridine lactate and double hose wind scattered.Methods A total of 102 cases of irritant dermatitis patients were randomly divided into two groups,each group had 51 cases.The control group was given traditional conventional methods nursing,while the intervention group was implemented ethacridine lactate and double hose wind scattered.Results The effective rate of intervention group was 88.24％,while the effective rate of control group was 66.67％.There was significant difference (P ＜ 0.01).Conclusions It is effective and safe that used ethacridine lactate and double hose wind scattered to treat pediatric irritant dermatitis.It is worthy of clinical application. Key words: Ethacridine lactate; Double hose wind scattered; Pediatric; Irritant dermatitis; Nursing

A severe dermatologic adverse effect related with gefitinib: Case report and review of the literature

Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine kinase, it's one of the most frequent drug-related adverse effects (AEs) reported in literature is dermatologic AEs. We report, a case of severe cutaneous adverse reactions induced by gefitinib as second-line treatment in a male patient with advanced non-small cell lung cancer after 1 month of treatment. Although tumor shrunk and patient got benefit from the treatment, gefitinib had to be stopped right away. We managed the symptoms of rash with a variety of treatments, including topical ethacridine lactate, antihistamine and so on. After the rash improved, we found his tumor were progress. Then he took gefitinib again without severe skin toxicity or disease progression. We think the development of gefitinib-induced rash may be a sign of effective and administrating it again maybe relieves the degree of rash.

Determining loading kinetics of drug releasing degradable shape-memory polymers

ABSTRACTModern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific biofunctionalities. Here, amorphous and semi-crystalline copolyester-based shape-memory polymer (SMP) networks are reported as matrix for pharmaceutical applications. Drug loading of such crosslinked networks by swelling techniques requires tools to determine the actual payload. In this report, the capability of determining loading kinetics by mass increase or changes of drug concentration in the swelling medium is explored for two types of copolyester-based SMP networks differing in their crosslinking chemistry. Nitrofurantoin and ethacridine lactate served as hydrophobic and hydrophilic model drugs. It was found, that the absolute values of the determined payload did not systematically agree with those obtained by the more reliable technique of network cleavage and spectrophotometric quantification. However, the studies indicate that for both types of SMP materials and both drugs, maximum incorporation of the drugs occurred within a few hours. The time until equilibration depended on the network properties.