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Biomedical subjects

M Papadaki

Publications and source records attributed to M Papadaki.

16 recordsLinked to original sources

Labd-14-ene-8,13-diol (sclareol) induces cell cycle arrest and apoptosis in human breast cancer cells and enhances the activity of anticancer drugs.

Sclareol is a labdane-type diterpene that has demonstrated a significant cytotoxic activity against human leukemic cell lines. Here, we report the effect of sclareol against the human breast cancer cell lines MN1 and MDD2 derived from the parental cell line, MCF7. MN1 cells express functional p53, whereas MDD2 cells do not express p53. Flow cytometry analysis of the cell cycle indicated that sclareol was able to inhibit DNA synthesis induce arrest at the G(0/1) phase of the cycle apoptosis independent of p53. Sclareol-induced apoptosis was further assessed by detection of fragmented DNA in the cells. Furthermore, sclareol enhanced the activity of known anticancer drugs, doxorubicin, etoposide and cisplatinum, against MDD2 breast cancer cell line.

Antineoplastic Agents↗

Field application of autometallography and X-ray microanalysis using the digestive gland of the common mussel.

The histological and ultrastructural localization of heavy metals in the digestive gland of the mussel, Mytilus galloprovincialis, was evaluated using autometallography and X-ray microanalysis on epoxy resin sections. Mussels were collected from two populations along Thermaikos gulf (port of Thessaloniki and Halastra) and one population in Strymonikos Gulf (Olympiada). With the use of autometallography, the light and electron microscopic observations indicated that in the digestive gland, the metals are localized in lysosomal structures, such as heterolysosomes and the residual bodies of digestive cells. Through both techniques, mussels collected from the port of Thessaloniki displayed concentrations of metals higher than those recorded in mussels from Halastra and Olympiada. This fact is consistent with other reports indicating a similar distribution of metals in Thermaikos Gulf and Strymonikos Gulf. The results of the study support the use of both techniques, autometallography and X-ray microanalysis, as a suite of stress indices for pollution biomonitoring studies.

Animals↗

Sonochemical degradation of phenolic pollutants in aqueous solutions.

The sonochemical degradation of phenol, 2-chlorophenol and 3,4-dichlorophenol in aqueous solutions as a function of several operating conditions has been investigated. Experiments were performed at initial substrate concentrations of 0.1, 0.5 and 1 g l(-1), liquid phase volumes of 0.05, 0.07 and 0.08 l, electric power outputs of 125, 187.5 and 250 W, liquid bulk temperatures of 20, 35, 50 and 70 degrees C and an ultrasound frequency of 20 kHz. Substrate concentration was determined as a function of time by means of high performance liquid chromatography. At the conditions under consideration, the rate of degradation follows first order kinetics with respect to the substrate concentration and increases with increasing electric power and decreasing liquid volume. The relative reactivity appears to decrease in the order: 2-chlorophenol > 3,4-dichlorophenol > phenol. Measurements of liquid phase total organic carbon content showed that degradation by-products are more recalcitrant than the original substrate. The rate of 2-chlorophenol degradation was also found to decrease with decreasing liquid bulk temperature and increasing initial concentration. Addition of t-butanol as a hydroxyl radical scavenger only partially inhibited degradation, thus implying that degradation is likely to proceed via both radical-induced and thermal reactions. Addition of Fe2+ ions at concentrations as low as about 0.2 x 10(3) g l(-1) resulted in increased degradation rates; this is attributed to iron being capable of readily decomposing hydrogen peroxide (generated by water sonolysis) in a Fenton-like process to form hydroxyl radicals as well as being an effective oxidation catalyst. The implications of the use of ultrasound in wastewater treatment are also discussed.

Kinetics↗

The different behaviors of skeletal muscle cells and chondrocytes on PEGT/PBT block copolymers are related to the surface properties of the substrate.

The attachment, proliferation, morphology, and differentiation of two cell types-skeletal muscle cells and chondrocytes-were investigated on different compositions of poly(ethylene glycol) and poly(butylene terephthalate) segmented block copolymers. Four weight percentages (40, 55, 60, and 70%) and two different molecular weights (300 and 1000 Da) of poly(ethylene glycol) were tested. Varying the weight percentage and molecular weight of poly(ethylene glycol) resulted in different behaviors for skeletal muscle cells and chondrocytes. The attachment of skeletal muscle was the highest (similar to tissue culture polystyrene) when copolymers containing 55 wt % of poly(ethylene glycol) were used, regardless of the poly(ethylene glycol) molecular weight. Maximum proliferation and differentiation of skeletal muscle cells was achieved when copolymers containing 55 wt % and 300 Da molecular weight of poly(ethylene glycol) were used. In contrast, the weight percentage and molecular weight of poly(ethylene glycol) had no significant effect on chondrocyte attachment and proliferation; the attached chondrocytes retained a differentiated phenotype only when a 70 wt % of poly(ethylene glycol) was used. Cell behavior was correlated with the surface properties of the copolymer films, as indicated by contact-angle measurements. These results suggest that an optimized wt % and molecular weight of poly(ethylene glycol) will be useful depending on the specific cell type.

Animals↗

Tissue engineering of functional cardiac muscle: molecular, structural, and electrophysiological studies.

The primary aim of this study was to relate molecular and structural properties of in vitro reconstructed cardiac muscle with its electrophysiological function using an in vitro model system based on neonatal rat cardiac myocytes, three-dimensional polymeric scaffolds, and bioreactors. After 1 wk of cultivation, we found that engineered cardiac muscle contained a 120- to 160-microm-thick peripheral region with cardiac myocytes that were electrically connected through gap junctions and sustained macroscopically continuous impulse propagation over a distance of 5 mm. Molecular, structural, and electrophysiological properties were found to be interrelated and depended on specific model system parameters such as the tissue culture substrate, bioreactor, and culture medium. Native tissue and the best experimental group (engineered cardiac muscle cultivated using laminin-coated scaffolds, rotating bioreactors, and low-serum medium) were comparable with respect to the conduction velocity of propagated electrical impulses and spatial distribution of connexin43. Furthermore, the structural and electrophysiological properties of the engineered cardiac muscle, such as cellularity, conduction velocity, maximum signal amplitude, capture rate, and excitation threshold, were significantly improved compared with our previous studies.

Animals↗

Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization.

Cardiac tissue engineering has been motivated by the need to create functional tissue equivalents for scientific studies and cardiac tissue repair. We previously demonstrated that contractile cardiac cell-polymer constructs can be cultivated using isolated cells, 3-dimensional scaffolds, and bioreactors. In the present work, we examined the effects of (1) cell source (neonatal rat or embryonic chick), (2) initial cell seeding density, (3) cell seeding vessel, and (4) tissue culture vessel on the structure and composition of engineered cardiac muscle. Constructs seeded under well-mixed conditions with rat heart cells at a high initial density ((6-8) x 10(6) cells/polymer scaffold) maintained structural integrity and contained macroscopic contractile areas (approximately 20 mm(2)). Seeding in rotating vessels (laminar flow) rather than mixed flasks (turbulent flow) resulted in 23% higher seeding efficiency and 20% less cell damage as assessed by medium lactate dehydrogenase levels (p < 0.05). Advantages of culturing constructs under mixed rather than static conditions included the maintenance of metabolic parameters in physiological ranges, 2-4 times higher construct cellularity (p &le 0.0001), more aerobic cell metabolism, and a more physiological, elongated cell shape. Cultivations in rotating bioreactors, in which flow patterns are laminar and dynamic, yielded constructs with a more active, aerobic metabolism as compared to constructs cultured in mixed or static flasks. After 1-2 weeks of cultivation, tissue constructs expressed cardiac specific proteins and ultrastructural features and had approximately 2-6 times lower cellularity (p < 0.05) but similar metabolic activity per unit cell when compared to native cardiac tissue.

Animals↗

Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities.

Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

Animals↗

Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies.

The objective of this study was to establish a three-dimensional (3-D) in vitro model system of cardiac muscle for electrophysiological studies. Primary neonatal rat ventricular cells containing lower or higher fractions of cardiac myocytes were cultured on polymeric scaffolds in bioreactors to form regular or enriched cardiac muscle constructs, respectively. After 1 wk, all constructs contained a peripheral tissue-like region (50-70 micrometer thick) in which differentiated cardiac myocytes were organized in multiple layers in a 3-D configuration. Indexes of cell size (protein/DNA) and metabolic activity (tetrazolium conversion/DNA) were similar for constructs and neonatal rat ventricles. Electrophysiological studies conducted using a linear array of extracellular electrodes showed that the peripheral region of constructs exhibited relatively homogeneous electrical properties and sustained macroscopically continuous impulse propagation on a centimeter-size scale. Electrophysiological properties of enriched constructs were superior to those of regular constructs but inferior to those of native ventricles. These results demonstrate that 3-D cardiac muscle constructs can be engineered with cardiac-specific structural and electrophysiological properties and used for in vitro impulse propagation studies.

Aging↗

Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells.

Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; P<0.05) at all examined time points (2 to 24 hours). mRNA half-life studies showed that this response was not due to increased mRNA instability. tPA mRNA expression was decreased (to 10% of stationary control; P<0.05) by low shear stress after 12 hours of exposure and was increased (to 250% of stationary control; P<0.05) after 24 hours at high shear stress. The same trends in PAR-1 mRNA levels were observed in rat smooth muscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

Aorta, Abdominal↗

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow.

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

Antibodies, Monoclonal↗

Effects of cognitive ability and affect on school mathematics performance and feelings of difficulty.

Research on cognitive ability and affect has indicated that both of them may function at various levels of generality (LG). This study aimed to investigate the possible effects of LG on school mathematics performance and related feelings of difficulty. Two hundred forty-three students of seventh, eighth, and ninth grades of both genders participated in the study. They were tested with cognitive ability tasks, affective questionnaires, and two school mathematics batteries. The difficulty of each of the school mathematics task was also rated on a 4-point scale. The two school mathematics batteries and affective questionnaires were re-administered 1 year after the first testing. Rates of difficulty were also taken. Path analysis showed that performance was mainly influenced by cognitive ability factors, whereas feelings of difficulty were influenced by performance, cognitive ability, and affective factors. The long-term relations between cognitive and affective factors are discussed.

Adolescent↗

New sonographic appearance of hepatic mesenchymal hamartoma in childhood.

We present clinical, radiographic, and sonographic findings in 3 children with hepatic mesenchymal hamartoma, a rare benign tumor of childhood. The presence of round hyperechoic parietal nodules within the cystic spaces of the hamartomas is a new sonographic finding.

Child, Preschool↗

Effects of fluid shear stress on gene regulation of vascular cells.

Hemodynamic forces such as fluid shear stress play an active role in many physiological and pathophysiological processes of the cardiovascular system. Shear stress resulting from blood flow and transmural plasma flux alters the function of vascular cell (primarily endothelial cells), leading to both rapid and slower adaptive tissue responses. Transmission of the shear stress signal throughout the vascular cell involves a complex interplay between cytoskeletal and biochemical elements and results in changes in structure, metabolism, and gene expression. Herein we review current knowledge on flow-induced mechanotransduction in the vascular endothelial cell and the molecular mechanisms believed responsible for shear-induced endothelial and smooth muscle cell gene regulation with an emphasis on signal transduction.

Animals↗