Bezmialem Vakıf Üniversitesi Kurumsal Akademik Arşiv
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    Fabric phase sorptive extraction combined with high performance liquid chromatography for the determination of favipiravir in human plasma and breast milk

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    A fast procedure obtained by the combination of fabric phase extraction (FPSE) with high performance liquid chromatography (HPLC) has been developed and validated for the quantification of favipiravir (FVP) in human plasma and breast milk. A sol-gel polycaprolactone-block-polydimethylsiloxane-block-polycaprolactone (sol-gel PCAP-PDMS-PCAP) coated on 100% cellose cotton fabric was selected as the most efficient membrane for FPSE in human plasma and breast milk samples. HPLC-UV analysis were performed using a RP C18 column under isocratic conditions. Under these optimezed settings, the overall chromatographic analysis time was limited to only 5 min without encountering any observable matrix interferences. Following the method validation pro-cedure, the herein assay shows a linear calibration curve over the range of 0.2-50 mu g/mL and 0.5-25 mu g/mL for plasma and breast milk, respectively. The method sensitivities in terms of limit of detection (LOD) and limit of quantification (LOQ), validated in both the matrices, have been found to be 0.06 and 0.2 mu g/mL for plasma and 0.15 and 0.5 mu g/mL for milk, respectively. Intraday and interday precision and trueness, accordingly to the International Guidelines, were validated and were below 3.61% for both the matrices. The herein method was further tested on real samples in order to highlight the applicability and the advantage for therapeutic drug monitoring (TDM) applications. To the best of our knowledge, this is the first validated FPSE-HPLC-UV method in human plasma and breast milk for TDM purposes applied on real samples. The validated method provides fast, simple, cost reduced, and sensitive assay for the direct quantification of favipiravir in real biological matrices, also appliyng a well-known rugged and cheap instrument configuration

    Electrocardiography and Drug Intoxication

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    Intoxication is the deterioration of body functions due to different toxic substances. Poisoning by drugs constitutes an important part of all poisonings. Symptoms such as altered consciousness, tachycardia/bradycardia, or hypertension/hypotension may be seen because the cardiovascular system is affected. Changes in clinical findings and ECG may be revealed according to the degree of heart involvement. Rapid recognition and effective intervention by the emergency physician are of great importance. This review considers the use of ECG in the management of poisoned patients. Systematic evaluation of the ECG in a patient followed up with poisoning is essential for details that may be overlooked. Velocity, rhythm, intervals, and segments, QRS, wave morphologies, durations, ischemic changes should be followed carefully. When performing rhythm analysis, clues to drug cardiotoxicity should be sought in unstable patients. Are there ectopic beats on the EKG? The answer to this question may carry important clues. Automaticity caused by sympathomimetics may underlie ectopic beats. This may be the first sign of a problem caused by acute coronary syndrome or electrolyte disturbances. Is the rhythm supraventricular? or ventricular? Is bradycardia with AV block? Or without AV block? Is tachycardia narrow complex? Or is it a large complex? Answers to questions such as: For life-threatening rhythms, ventricular tachycardia, ventricular fibrillation, and complete AV-block, the guidelines developed should be followed, and first intervention should be made. Agents that can cause tachycardia; are sympathomimetics (methamphetamine), anticholinergics (antidepressants, antipsychotics), class 1A and 1C antidysrhythmics, and TCA. Agents that can cause bradycardia; calcium channel / beta blockers / digoxin (AV block), opioids / ethanol, organophosphates, lithium. Prolonging the PR interval may indicate beta-adrenergic antagonism, calcium channel antagonism, or digoxin poisoning. Typical ECG of TCA poisoning shows sinus tachycardia with first-degree AV block, wide QRS complexes, and positive R\" wave in aVR. The ECG should be taken and evaluated in patients presenting with poisoning within the first 10 minutes. Suppose the poisoning agent is an agent that influences the cardiovascular system. In that case, it should be kept in mind that continuous cardiac monitoring and control ECG evaluation should be performed in addition to the application of ECG

    Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice

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    The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity display variations depending on the chronopharmacokinetics. For anticancer drugs with narrow therapeutic ranges and dose-limiting side effects, it is particularly important to know the temporal changes in pharmacokinetics. A previous study indicated that pharmacokinetic profile of capecitabine was different depending on dosing time in rat. However, it is not known how such difference is attributed with respect to diurnal rhythm. Therefore, in this study, we evaluated capecitabine-metabolizing enzymes in a diurnal rhythm-dependent manner. To this end, C57BL/6J male mice were orally treated with 500 mg/kg capecitabine at ZT1, ZT7, ZT13, or ZT19. We then determined pharmacokinetics of capecitabine and its metabolites, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results revealed that plasma Cmax and AUC0-6h (area under the plasma concentration-time curve from 0 to 6 h) values of capecitabine, 5′DFUR, and 5-FU were higher during the rest phase (ZT1 and ZT7) than the activity phase (ZT13 and ZT19) ( p < 0.05). Similarly, Cmax and AUC0-6h values of 5′DFUR and 5-FU in liver were higher during the rest phase than activity phase ( p < 0.05), while there was no significant difference in liver concentrations of capecitabine and 5′DFCR. We determined the level of the enzymes responsible for the conversion of capecitabine and its metabolites at each ZT. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase ( p < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects

    The effects of maternal smoking on fetal cranial development. Findings from routine midtrimester sonographic anomaly screening

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    The aim of this study was to assess the effect of continued smoking before and during pregnancy on mid-trimester fetal head development. A total of 250 pregnant women enrolled in the study. All participants were confirmed to be smokers or non-smokers by verifying breath carbon monoxide readings. Biparietal diameter (BPD), head circumference (HC), lateral ventricle (LV), and cisterna magna (CM) were evaluated by ultrasound between 20-22 weeks of pregnancy. Gender and gestational age-adjusted BPD z- scores were not statistically different between smokers and non-smokers (-0.75 ± 1.6 vs -0.51 ± 1, p = .3). HC measurements and z- scores were significantly lower in the smoking group than in the non-smoking groups (183.38 ± 14.56 vs. 189.28 ± 12.53, p = .003, 0.18 ± 1.39 multiple of median (MoM) vs. 0.56 ± 0.92, respectively, p = .023). At linear regression analysis, maternal smoking was the only independent factor associated with fetal HC z score (p = .041). In conclusion, continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV, or CM measurements at mid-gestation.IMPACT STATEMENTWhat is already known on this subject? Smoking during pregnancy is one of the most common environmental factors affecting fetal and neonatal growth and well-being. Despite the well-known effects of smoking on somatic growth, current studies have shown that it selectively affects some parts of the fetal brain, even in appropriately growing fetuses.What do the results of this study add? Continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV or CM measurements at mid-gestation. Since smoking is well known for its early and late childhood behavioral and neurological consequences, smaller mid-trimester fetal HC measurements should bring maternal smoking to mind as one of the potentially reversible causes.What are the implications of these findings for clinical practice and/or further research? The harmful effects of smoking start before the third trimester and antenatal counseling should be started early in the gestation. Every effort should be made to quit smoking before or early in pregnancy

    Anti-microbial, anti-oxidant and wound healing capabilities of Aloe vera-incorporated hybrid nanoflowers

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    © 2023 The Society for Biotechnology, JapanThe active ingredients of Aloe vera have attracted attention for their potential use in nanotechnology-based medical applications and biomaterial production. It has many therapeutic applications in modern world. This study used Aloe vera extract in different concentrations to synthesize Aloe vera-incorporated hybrid nanoflowers (AV-Nfs). The most uniform morphology in the nanoflowers obtained was at a concentration of 2 mL. The AV-Nfs were well characterized by scanning electron microscopy, X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction (XRD). The highest peroxidase-mimicking activity of the components was 1.488 EU/mg at 60°C and pH 6. The DPPH assay determined the antioxidant activity of the components and the MTT assay tested on CCD-1072Sk fibroblast cell line determined the effect of AV-Nfs on cell proliferation. Separate treatment of AV-Nfs with Cu3(PO4)2·3H2O significantly increased cell proliferation according to free Aloe vera and CuSO4. In vitro wound healing results showed that AV-Nfs could significantly close wounds compared to free Aloe vera. In this study, AV-Nfs showed antimicrobial activity against Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli and Klebsiella pneumoniae at minimum inhibitory concentration of 625 μg/mL, suggesting that AV-Nfs may be used in wound healing applications with enhanced biological properties. AV-Nfs showed no activity against the yeast Candida albicans

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    Bezmialem Vakıf Üniversitesi Kurumsal Akademik Arşiv
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