Effect of structural modification at the 4, 3′, and 2′ positions of doxorubicin on topoisomerase II poisoning,apoptosis, and cytotoxicity in human melanoma cells

Introduction: The mechanism of the cytotoxicity of anthracyclines is pleiotropic and its significance in cell growth inhibition seems to be highly specific and dependent on cell type and anthracycline drug. Resistance and the high cardiotoxicity of anthracyclines have stimulated many studies aimed at identifying critical substituents required for optimal activity. Many authors point to the fact that the double-strand breaks, the consequence of the activity of topoisomerase II poisons, and the inability of cells to repair the DNA lesions are the signal for apoptosis. The aim of this study was to define the influence of 4-demetoxy 2’-halogenated analogs with altered basicity at the 3’-position on topoisomerase II and the relationship of that interaction with apoptosis and the cytotoxicity of these novel anthracyclines. Parental human ME18 melanoma cells and the ME18/R subline, obtained experimentally, resistant to doxorubicin (DOX), exposed to 1.7 and 8.6 μM DOX or its analogs, annamycin and WP903 (both 0.3 and 3.0 μM) were studied. Materials and Methods: The MTT test was used to assay cytotoxicity. Interaction of the drugs with topoisomerase II and apoptosis were done by Western blot and fluorescence microscopy using Hoechst 33342. Results: The structural changes at positions 4, 2’, and 3’ can influence topoisomerase II interaction and apoptotic activity, although correlation between these events and cytotoxic consequences has not been proved. Conclusions: The biological response of the cells to the structurally similar anthracyclines may be variable and probably depends on the cell type which seems to be an additional problem in the multifactorial resistance of tumor cells to anthracyclines.     

Asbestosis--physical examination and symptoms

The study included 318 asbestos exposed workers. The aim was to investigate the symptomatology and clinical findings over an average period of ten years. We took in cosideration quantitative data and analyzed them by statistical methodology of univariate and multivariate data analysis and chi2-test. Chest radiography, clinical and functional findings were used as a diagnostic tool. The most common finding was dyspnea, then cough and chest pain. Clinical symptoms were more common in workers exposed to crysotile asbestos than in those exposed to crocidolite asbestos. There is strong evidence for association between the symptoms and the duration of asbestos exposure. The symptoms were not specific for asbestosis. A significant positive correlation was found between physical examination and duration of asbestos exposure. Basal rales and pleural rub were recorded in 72% of exposed workers.     

Chromosomal study of Khawia abbottinae (Cestoda: Caryophyllidea): karyotype and localization of telomeric and ribosomal sequences after fluorescence in situ hybridization (FISH)

Parasitology Research - An original cytogenetic study combining classical karyotype analysis and modern fluorescence in situ hybridization using telomeric (TTAGGG)n and ribosomal sequences (18S...     

Prevalence of the most common high-risk HPV genotypes among women in three new independent states of the former Soviet Union

Type distribution of HPV has been studied in different geographic regions, but the data are scanty from the new independent states of the former Soviet Union. Here the HPV prevalence and distribution of the most frequent high-risk HPV types among 3,187 women at different risk for HPV and cervical intraepithelial neoplasia in Russia, Belarus, and Latvia is reported. HPV detection, type distribution and viral load analysis in DNA samples from cervical scrapes were done with real-time PCR-based assay detecting HPV types 16, 18, 31, 33, 35, 39, 45, 52, and 58. The overall HPV prevalence was 31.2%, HPV16 was the most prevalent type followed by HPV31 and HPV33 group. The overall HPV prevalences in Russia, Belarus and Latvia were 33.4%, 27.5%, and 26.2%. The type distributions were similar in these countries, except for Latvia where HPV39 was the third prevalent genotype. HPV prevalence was highest (40.8%) among women from sexually transmitted disease clinic, followed by 30.9% among gynecological outpatients and 27.2% in screening patients. HPV detection increased with cytological abnormality (P = 0.0001) and lesion grade in the biopsy (P = 0.0001), from 27% to 72% in normal samples to cancer, and from 64% to 77% in cervical intraepithelial neoplasia 1 to cancer. The normalized viral loads varied greatly between and among different HPV-types. The mean log HPV33 group copies/cell increased from negative for intraepithelial lesions to cancer (P = 0.049). Distribution of the most common high-risk HPV-types seems to be similar in these countries as reported in other major geographical regions.     

Six-Month Emergency Department Use among Older Adults Following Jail Incarceration

Although the number of older adults who are arrested and subject to incarceration in jail is rising dramatically, little is known about their emergency department (ED) use or the factors associated with that use. This lack of knowledge impairs the ability to design evidence-based approaches to care that would meet the needs of this population. This 6-month longitudinal study aimed to determine the frequency of 6-month ED use among 101 adults aged 55 or older enrolled while in jail and to identify factors associated with that use. The primary outcome was self-reported emergency department use within 6 months from baseline. Additional measures included baseline socio-demographics, physical and mental health conditions, geriatric factors (e.g., recent falls, incontinence, functional impairment, concern about post-release safety), symptoms (pain and other symptoms), and behavioral and social health risk factors (e.g., substance use disorders, recent homelessness). Chi-square tests were used to identify baseline factors associated with ED use over 6 months. Participants (average age 60) reported high rates of multimorbidity (61%), functional impairment (57%), pain (52%), serious mental illness (44%), recent homelessness (54%), and/or substance use disorders (69%). At 6 months, 46% had visited the ED at least once; 21% visited multiple times. Factors associated with ED use included multimorbidity (p = 0.01), functional impairment (p = 0.02), hepatitis C infection (p = 0.01), a recent fall (p = 0.03), pain (p < 0.001), loneliness (p = 0.04), and safety concerns (p = 0.01). In this population of older adults in a county jail, geriatric conditions and distressing symptoms were common and associated with 6-month community ED use. Jail is an important setting to develop geriatric care paradigms aimed at addressing comorbid medical, functional, and behavioral health needs and symptomatology in an effort to improve care and decrease ED use in the growing population of criminal justice-involved older adults.     

Clinical study of the color stability of veneering ceramics for zirconia frameworks

PURPOSE: The purpose of this study was to compare 3 veneering ceramics for zirconia frameworks regarding color stability and predictability of the esthetic result. Materials AND METHODS: Six patients with 1 maxillary central incisor to be restored were enrolled in the study. The contralateral incisor had to be nonrestored and vital to serve as a reference tooth. For each patient, 4 single crowns with zirconia frameworks were fabricated. Three veneering ceramics were assessed and masked to eliminate bias. Choice of the veneering ceramics was done at random. The veneering was performed by 4 dental technicians. Three veneering ceramics were compared: ceramic A (Initial, GC), ceramic B (Triceram, Esprident), and ceramic C (Cercon Ceram S, DeguDent). The color of the crowns and reference teeth was captured using spectrophotometric analysis (SpectroShade, MHT), and the color difference (deltaE) was calculated (objective method). In addition, the crowns and reference teeth were compared subjectively by 11 observers blind to the ceramic used for veneering. Statistical analysis was performed with analysis of variance (ANOVA). RESULTS: Regardless of the veneering ceramic used, all crowns showed a high color deviation from the reference teeth when applying the objective analysis (deltaE(A) 6.8 +/- 2.5, deltaE(B) 5.6 +/- 1.2, deltaE(C) 5.7 +/- 2.1). In addition, no significant differences were found between the deltaE of crowns and teeth for the 3 ceramics. In the framework-supported area, ceramic B showed a significantly lower difference in value (deltaL) compared to the reference teeth than the other 2 ceramics (deltaL(A) 4.9 +/- 2.3, deltaL(B) 1.1 +/- 2.1, deltaL(C) 4.1 +/- 1.5; P < .01 ANOVA). When performing the subjective analysis, ceramic B was chosen as the best match by a majority of observers (> 60%) in 4 of 6 patients. CONCLUSIONS: All 3 ceramics met the esthetic demands only to a limited extent. Ceramic B allowed for the most predictable result in terms of color stability.     

Characterization of drug release from fibrin gels loaded with different pharmaceutical and experimental doxorubicin formulations

Background

Local delivery of anticancer drugs represents a desirable type of treatment. Nevertheless, characteristics such as availability, biocompatibility, ease of operation, and efficacy sometimes represent difficult to overcome hurdles. Fibrin gels (FBGs) may be attractive biomaterials for local treatment when loaded with different chemotherapeutics or with polymer-anticancer-drug conjugates and nanoparticles. These components, linked together, might represent candidates to counteract local recurrences or reduce the volume of inoperable tumors. In the present study we analyzed the features of in vitro release of different formulations of doxorubicin (DOXO) from FBGs, and in vivo FBGs degradation.

Validation of self assessment patient knowledge questionnaire for heart failure patients.

BACKGROUND: Several studies showed insufficient knowledge and poor compliance to non-pharmacological management in heart failure patients. Only a limited number of validated tools are available to assess their knowledge. The aim of the study was to test our 10-item Patient knowledge questionnaire. METHODS: The Patient knowledge questionnaire was administered to 42 heart failure patients from Heart failure clinic and to 40 heart failure patients receiving usual care. Construct validity (Pearson correlation coefficient), internal consistency (Cronbach alpha), reproducibility (Wilcoxon signed rank test), and reliability (chi-square test and Student's t-test for independent samples) were assessed. RESULTS: Overall score of the Patient knowledge questionnaire had the strongest correlation to the question about regular weighing (r=0.69) and the weakest to the question about presence of heart disease (r=0.33). There was a strong correlation between question about fluid retention and questions assessing regular weighing, (r=0.86), weight of one litre of water (r=0.86), and salt restriction (r=0.57). The Cronbach alpha was 0.74 and could be improved by exclusion of questions about clear explanation (Chronbach alpha 0.75), importance of fruit, soup, and vegetables (Chronbach alpha 0.75), and self adjustment of diuretic (Chronbach alpha 0.81). During reproducibility testing 91% to 98% of questions were answered equally. Patients from Heart failure clinic scored significantly better than patients receiving usual care (7.9 (1.3) vs. 5.7 (2.2), p<0.001). CONCLUSIONS: Patient knowledge questionnaire is a valid and reliable tool to measure knowledge of heart failure patients.