Poly(octamethylene citrate) Modified with Glutathione as a Promising Material for Vascular Tissue Engineering.

One of the major goals of vascular tissue engineering is to develop much-needed materials that are suitable for use in small-diameter vascular grafts. Poly(1,8-octamethylene citrate) can be considered for manufacturing small blood vessel substitutes, as recent studies have demonstrated that this material is cytocompatible with adipose tissue-derived stem cells (ASCs) and favors their adhesion and viability. The work presented here is focused on modifying this polymer with glutathione (GSH) in order to provide it with antioxidant properties, which are believed to reduce oxidative stress in blood vessels. Cross-linked poly(1,8-octamethylene citrate) (cPOC) was therefore prepared by polycondensation of citric acid and 1,8-octanediol at a 2:3 molar ratio of the reagents, followed by in-bulk modification with 0.4, 0.8, 4 or 8 wt.% of GSH and curing at 80 °C for 10 days. The chemical structure of the obtained samples was examined by FTIR-ATR spectroscopy, which confirmed the presence of GSH in the modified cPOC. The addition of GSH increased the water drop contact angle of the material surface and lowered the surface free energy values. The cytocompatibility of the modified cPOC was evaluated in direct contact with vascular smooth-muscle cells (VSMCs) and ASCs. The cell number, the cell spreading area and the cell aspect ratio were measured. The antioxidant potential of GSH-modified cPOC was measured by a free radical scavenging assay. The results of our investigation indicate the potential of cPOC modified with 0.4 and 0.8 wt.% of GSH to produce small-diameter blood vessels, as the material was found to: (i) have antioxidant properties, (ii) support VSMC and ASC viability and growth and (iii) provide an environment suitable for the initiation of cell differentiation.

Advancements in structure-property correlation studies of cross-linked citric acid-based elastomers from the perspective of medical application.

Herein, a renewed prominence towards the synthesis of poly(alkylene citrate) (PAC) biomaterials and their detailed chemical, structural and mechanical characterization has been reported. Based on the modifications to the PAC synthesis protocol introduced in this study, the fabrication process was significantly streamlined, the reaction yields were increased, and the homogeneity of the final materials was found to be substantially improved. Comprehensive nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) studies of the fabricated prepolymers shed light on the mechanism of the PAC cross-linking process and supported the design of materials with enhanced biocompatibility. Therefore, the initial molar ratio of the reagents involved in the synthesis of PAC materials was found to be pivotal to both the biological and mechanical properties of the final products. Moreover, cell viability and proliferation assays revealed enhanced biocompatibility of the materials formulated with a molar ratio of diol over citric acid (3 : 2 mol/mol) in comparison to the most commonly described 1 : 1 analogue without affecting the possibility of further functionalization. Furthermore, this work creates a new paradigm for prospective studies on the properties of modified PAC materials and their application in medicine and tissue engineering.

Fluorescence assay for the determination of glutathione based on a ring-fused 2-pyridone derivative in dietary supplements.

Herein, a novel fluorescent method for the determination of GSH levels in aqueous solutions involving the utilization of citric acid as a derivatization reagent was developed. Therefore, the crucial parameters of the derivatization process were established from what has resulted in the development of a sensitive, reproducible, and accurate GSH assay. The method was validated, and its applicability in the characterization of the GSH concentration in dietary supplements concerning the selectivity in the determination of GSH over GSSG was both confirmed. The chemical structure of the new fluorophore 3-[(carboxymethyl)carbamoyl]-5-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyridine-7-carboxylic acid - CTPC was elucidated using detailed NMR: one-dimensional (1H, 13C), as well as two-dimensional NMR spectra (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC, 1H-15N HSQC, 1H-15N HMBC) experiments. Besides, the essential optical, biological and antioxidative properties of CTPC were investigated.

Drug-safety reporting in Polish nursing practice-Cross sectional surveys.

INTRODUCTION: Nurses play a significant role in ensuring the safety and quality of drugs. Our aim was to assess significant factors in nurses' participation in ensuring pharmacotherapy safety by reporting adverse drug reactions (ADR) and detecting substandard drugs (SD). MATERIALS AND METHODS: The study was a cross-sectional, comparative survey, using original questionnaires. Survey questions were grouped to probe the opinions, attitudes and practices of nurses reporting ADRs and SDs. Data were obtained from nurses working in teaching hospitals in Poland (group A) and, for comparison, in the USA (group B). 1200 questionnaires were distributed in Poland (return rate: 55.7%) and 200 questionnaires in the USA (return rate: 73%). Both groups were surveyed during the same period. There were no exclusion criteria. The questionnaires were self-administered. Distribution and collection were anonymous. Participation was voluntary. The Spearman correlation test was used. Both groups' responses were cross-tabulated and compared using Fisher's Exact Test for Count Data. RESULTS: The study group comprised 669 Polish and 146 American professionally active nurses working in general care and surgical departments. Age range: 18 to 72 years. Median job seniority: 18.3 years (group A) and 20.6 years (group B). Education levels varied. ADR reporting conditions in Poland are unfavorable: shortage of time-83.9% vs 22.6% in the US (p = 0.01); no incentive-58.2% vs 6.1% in the US (p = 0.01); and no equipment-44.7% vs 2.8% in the US (p < 0.01). Both Polish and American nurses indicate they rarely report SDs, with rates of 0.4% and 11% (p < 0.0001) respectively, during the study period. CONCLUSIONS: Nurses in Poland are insufficiently prepared to ensure drug safety conscientiously and responsibly. Training is required for Polish nurses. Nurses' employers need to improve conditions to enable reporting of ADRs and SDs.

ADVERSE DRUG REPORTING IN COMMUNITY PHARMACY PRACTICE IN THE POMERANIAN DISTRICT IN POLAND.

The changing role of the modern pharmacies involves reporting adverse drug reactions (ADR's). The aim of the study is to investigate the knowledge of community pharmacy professional staff (PS) about the new pharmacovigilance (PG) legislation and to analyze patients' attitudes towards the community pharmacy role in PG across north central region in Poland. Research material was collected in a group of pharmacy PS and patients from January 2014 to August 2014 in the Pomeranian District. A cross-sectional study was conducted. The research project consisted of three single anonymous surveys. Main outcome measure was knowledge of PS towards ADRs reporting, attitudes of patients towards ADRs in relation to PS in a community pharmacy. Over half of surveyed pharmacists (54.7%) and only 13% of pharmaceutical technicians know the correct and current definition of ADR. PS do not know what kind of ADRs should be reported - only 41% of pharmacists and 12.1% of technicians presented adequate knowledge. As far as the knowledge of where to notify is concerned - it was present in 60.7% of pharmacists and only 11.2% of pharmaceutical technicians. In most cases pharmacists (72%) know that patients can make their own notifications, technicians showed such knowledge only in 37.4% of cases. Patients who detect an ADR occurrence often do not transmit the information (19% of respondents). However, if they decide to report, they mostly talk to physicians (76.6%), and, less frequently (14.6%), to pharmacy PS. In the opinion of patients, however, the pharmacy PS (20.3%) are identified as sub- jects involved in reporting ADRs and those who can transmit information on the ADRs. The results suggest that pharmacists' knowledge of the rules of reporting ADRs is superior to that of pharmaceutical technicians. In fact, PS are not sufficiently prepared for reporting ADRs. Patients, in turn, do not have adequate awareness of reporting the observed ADRs. They, however, associate the community pharmacy with PG system, although the extent is unsatisfactory. In this regard, a more effective training of PS would be recommended along with tailored social campaigns to inform about the PG system in Poland.

Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB.

INTRODUCTION: The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB) and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. MATERIAL AND METHODS: Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively). The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. RESULTS: In the control group the average number of mRNA copies was 134 ± 36 (median: 106), in a group with stage IB it was 16 077 ± 7090 (median: 580), for stage IIB - 35 019 ± 8945 (median: 40 870). The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. CONCLUSIONS: In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C, are expressed, which expression increases as the clinical stage of cervical cancer is higher.

[Significance of the DNA-HPV research in cervical cancer prevention]. / Znaczenie badan wykrywajacych DNA-HPV w profilaktyce raka szyjki macicy.

The purpose of our research was to assess DNA-HPV frequention observation and evaluation of the diagnostic value mRNA E6 and E7 HPV16 and HPV18 profile concentration in prognostic risk of intraepithelial lesions and cervical cancer progression in women with cytological screening. Human papilloma virus (HPV) infection were detected in 13.8% normal samples, presence HPV16 and 18 in 7.5% samples were detected. HPV 16, 18 or HPV16 and 18 infection were detected in 85% HSIL (high-grade squamous intraepithelial lesion) samples. HPV16 or HPV18 infection in 100% cancer samples were detected. In samples from control group expression of E6 and E7 genes were not detected. In LSIL (low-grade squamous intraepithelial lesion) group HPV16 E7 gene in 2.6% samples, in HSIL group E7 gene in 9.5% samples were detected. In all cancer samples E7 or E6 HPV16 and/or HPV18 were detected.