Synthesis and antiproliferative activity in vitro of 2-aminobenzimidazole derivatives

A novel series of Schiff bases 1-11, the derivatives of 2-aminobenzimidazole and substituted aromatic aldehydes, has been synthesised. Compounds 1-11 reduced by NaBH(4) formed 2-benzylaminobenzimidazoles 12-21. 2-(o-Bromobenzylamino)benzimidazole (15) acylated by cinnamoyl chloride gave 2-(o-bromobenzylamino)-1-cinnamoylbenzimidazole (22). Long heating of 15 and 19 with p-nitrocinnamoyl or cinnamoyl chloride led to the formation of pyrimido[1,2-a]benzimidazol-4-ones 23 and 24. The structures of 1-24 were identified by the results of elemental analysis and their IR, (1)H NMR and MS spectra. Among the compounds 1-24 evaluated for their antiproliferative activity in vitro, 16, 19, 20 and 22 exhibited cytotoxic activity against the cells of human cancer cell lines, namely SW707 (rectal), HCV29T (bladder), A549 (lung) and T47D (breast cancer).     

Perception of neoplasms and prophylactic measures

OBJECTIVES: Breast cancer is one of the most frequently medical problems of Polish women. DESIGN: The aim of the study was to answer the question, if imagination of neoplasm disease influence the undertaking of prophylactic activity by nurses and midwives. MATERIALS AND METHODS: Study was carried out among 202 female students from the Faculty of Nursing and Health Studies at the University Medical School in Lublin. Study was carried on the basis of the author's questionnaire. RESULT: Nearly half (99, that is 49.0%) respondents associated neoplasm's disease with suffering resulting in death. The majority (146, it means 72.3%) of women said that they had informed others of guidelines on breast self-control. Only 31.7% of respondents wrote that they practise breast self-examination on a regular basis. CONCLUSIONS: Imagination of neoplasm's disease did not influence regularity of self-examination and undertaking of prophylactic activity against breast cancer.     

Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine normal and growth retarded fetus.

OBJECTIVE: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation.

OBJECTIVES: The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies. PATIENTS AND METHODS: The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method. RESULTS: There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood. CONCLUSIONS: It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

The Immunomodulatory Activity of Staphylococcus aureus Products Derived from Biofilm and Planktonic Cultures

Biofilms are probably one of the most common structures formed by microorganisms in various environments. The higher resistance of such microbial communities to stress conditions, including antibiotics and host immune response, is recently extensively studied. However, the weak activity of phagocytic cells against microbial biofilm is not yet fully understood and explained. The aim of this study was: (1) a qualitative and quantitative comparison of cell components/products released from Staphylococcus aureus biofilm or planktonic cultures, (2) evaluation of the influence of such cell components/products on murine leukocytes secretory function. For this, mouse peritoneal leukocytes were stimulated with biofilm or planktonic staphylococcal cultures or their acellular filtrates, and then the production of cytokines (TNF-α, IL-6, IL-10, MCP-1 and MIP-1α), hemolytic activity and staphylokinase (SAK) production was determined. It was found that similar staphylococcal components/products possessing the immunomodulatory properties, were present in both, biofilm and planktonic filtrates. Moreover, these compounds were similarly active in the stimulation of TNF-α and MCP-1 release from leukocytes. The hemolytic activity and SAK release by planktonic and biofilm cultures were also comparable. What is interesting, stronger stimulatory activity of biofilm-derived components/products of clinical S. aureus strains in the case of MIP-1α, IL-6 and IL-10 was noticed. On the other hand, taking into consideration the reference strains, MIP-1α production was enhanced by “planktonic filtrates”. Thus, in our study it was proved, first of all, that biofilm is not a structure fully separated from the external environment. Second, the influence of these S. aureus constituents/metabolites on leukocytes seems to be more strain-dependent than culture phenotype-dependent. The lack of one common profile of biofilm and planktonic S. aureus cultures/filtrates biological activity indicates that the disturbances in cytokines’ production could not be the only reason for the so-called “frustrated phagocytosis”, connected with enhanced biofilm resistance.     

Smoothened is a master regulator of adult liver repair

When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell types that accumulate transiently during successful wound healing, including myofibroblasts (MFs) and progenitors. This suggests that signaling that normally directs these cells to repair injured epithelia is deregulated. To evaluate this possibility, we examined liver repair during different types of liver injury after Smoothened (SMO), an obligate intermediate in the Hedgehog (Hh) signaling pathway, was conditionally deleted in cells expressing the MF-associated gene, αSMA. Surprisingly, blocking canonical Hh signaling in MFs not only inhibited liver fibrosis but also prevented accumulation of liver progenitors. Hh-sensitive, hepatic stellate cells (HSCs) were identified as the source of both MFs and progenitors by lineage-tracing studies in 3 other strains of mice, coupled with analysis of highly pure HSC preparations using flow cytometry, immunofluorescence confocal microscopy, RT-PCR, and in situ hybridization. The results identify SMO as a master regulator of hepatic epithelial regeneration based on its ability to promote mesenchymal-to-epithelial transitions in a subpopulation of HSC-derived MFs with features of multipotent progenitors.     

Immune tolerance after delivery of dying cells to dendritic cells in situ

Peripheral immune tolerance is believed to be induced by the processing and presentation of self-tissues that die during physiologic tissue turnover. To examine the mechanism that mediates tolerance, we injected mice with dying syngeneic TAP(-/-) splenocytes loaded with small amounts of the protein antigen, ovalbumin (OVA). After ingestion and presentation of cell-associated OVA by the CD8(+) subset of dendritic cells in situ, large numbers of antigen-reactive, CD8(+) T cell receptor (TCR) transgenic T lymphocytes were driven into cell cycle, but then the T cells were deleted. The animals were also tolerant to challenge with OVA in complete Freund's adjuvant. An agonistic anti-CD40 monoclonal antibody was then administered together with the OVA-loaded splenocytes, so that the dendritic cells in the recipient mice would mature. In contrast to observations made in the steady state, the antigen-reactive T cells expanded in numbers for 1-2 wk and produced large amounts of interleukin 2 and interferon gamma, while the animals retained responsiveness to antigen rechallenge. The specific tolerance that develops when dendritic cells process self tissues in the steady state should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection.     

Advanced endoscopic imaging methods for colon neoplasia

The main goal of lumenal endoscopic visualization of the colon is to detect mucosal pathologies, which when removed will result in cure or palliation of a disease process. Whereas traditionally endoscopic imaging was performed with fiber-optic technology, currently there are many new methods that improve our visual acuity when evaluating the colon mucosa. Most of these methods are collectively called 'advanced colonic imaging'. The 2 main aims of standard (white light) and advanced colonic imaging are to enhance the superficial mucosal detail (i.e. 'pit pattern') and allow a detailed view of the submucosal capillary pattern, thus potentially improving the detection characterization of pathological lesions. However, the current literature dealing with most methods used for advanced endoscopic imaging of the colon is fraught with many controversial findings which have resulted in opposing views regarding its utility. Whereas some investigators vehemently support the use of most of these methods in routine clinical practice, most experts and practicing endoscopists still refuse to accept that these methods aid in the clinical routine. For now, white light video-colonoscopy and high-definition white light video-colonoscopy will remain the standard endoscopic methods for investigating the colon mucosa until new methods convincingly and clearly prove their superiority over white light endoscopy.